Technical field
[0001]The present invention relates to an organic synthesis, especially peptide synthesis and the like, specific benzyl compounds that can be used as a protective reagent amino acid or a carboxyl group or C-terminus of the peptide in, and a peptide synthesis method using the benzyl compounds.
BACKGROUND
[0002]The peptide synthesis method, in addition to the solid phase method and liquid phase method, in recent years, the reaction was carried out in homogeneous liquid phase, the protecting group after the reaction by changing the solvent composition capable only filtration and washed with isolation and purification (hereinafter , also referred to as anchors.) manufacturing method using have been proposed.
[0003]Patent Document 1 and Non-Patent Document 1, each technique of the 3,4,5-tris (n- octadecyl) benzyl alcohol type compound and the protective reagent such as a carboxyl group is disclosed. However, for alkyl-suppressing effect during removal of the protecting group was not any description.
[0004]Patent Documents 2 to 4 are respectively 3,5-di (docosyloxy) benzyl alcohol type compounds, 2,4-di (docosyloxy) protecting reagent such as benzyl alcohol-type compound is disclosed. However, for alkyl-suppressing effect during removal of the protecting group was not any description.
[0005]
　Patent Document 4 discloses also protected reagents trityl type. However, the protecting group like also side reactions fall off occurs even in methanol, was not always satisfactory as an anchor.
CITATION
Patent Document
[0006]
Patent Document 1: JP 2000-44493 JP
Patent Document 2: WO 2006/104166 Pamphlet
Patent Document 3: WO 2007/034812 pamphlet
Patent Document 4: WO 2007/122847 pamphlet
Non-patent literature
[0007]
Non-Patent Document 1: Bull. Chem. Soc. Jpn. , 74,733-738 (2001)
Summary of the Invention
Problems that the Invention is to Solve
[0008]
　An object of the present invention, the organic synthesis reaction performed in homogeneous liquid phase, after the reaction by changing the solvent composition used as a protecting group that allows only filtration and washed with isolation and purification (Anchor) obtained, alkylation at acidic conditions while inhibiting the reaction, it is deprotected in a high yield, is that to obtain a high purity product to provide useful benzyl compounds that can.
Means for Solving the Problems
[0009]
　The present inventor has found the above problems can be solved by a particular benzyl compounds having only one was substituted hydroxyl by an organic group having 14 or more aliphatic hydrocarbon group having a carbon, and have completed the present invention . The present invention is as follows.
[1] formula (I):
[0010]
[Formula 1]

[0011]
Wherein,
Y represents a hydroxyl group or a group -NHR (R is a hydrogen atom, an alkyl group or an aralkyl group.);
R a represents an organic group having an aliphatic hydrocarbon group, the organic group the total number of carbons in There are 14 or more;
n number of R b are each independently an alkoxy group having 1 to 6 carbon atoms, halogen atoms or one or more carbon atoms which may be substituted with a halogen atom, It represents an alkyl group having 1 to 6; and
n represents an integer of 0-4. ]
Benzyl compound represented by.
[2] R a total number of carbons in the organic group having an aliphatic hydrocarbon group is 14 to 200, [1] benzyl compounds described.
[3] R a total number of carbons in the organic group having an aliphatic hydrocarbon group of 30-80, [1] benzyl compounds described.
[4] n is an integer from 0 to 2, and,
n pieces of R b are each independently an alkoxy group having 1 to 4 carbon
atoms, in any one of [1] to [3] benzyl compounds described.
[5] R A is represented by the formula (a):
[0012]
[Formula 2]

[0013]
Wherein
* indicates the binding
position; m 1 represents an integer of 1 ~
10; m 1 pieces of X 1 are each independently a single bond, or -O -, - S -, - COO -, - OCONH -, - NHCO- or -CONH-
indicates; R 1 and m 1 pieces of R 2 are each independently a divalent aliphatic hydrocarbon group having 5 or more carbon atoms It is shown; and
R 3 is a hydrogen atom or the formula, (I '):
[0014]
[Formula 3]

[0015]
(Wherein, * represents a binding position;
the other symbols, as defined for [1].) Is a group represented by. ] Group represented by;
formula (b):
[0016]
[Chemical Formula 4]

[0017]
(Wherein,
* represents a bonding
position; m 2 is 1 or 2 are
shown; n 1 , n 2 , n 3 and n 4 are each independently an integer of 0 ~
2; m 2 number of X 2 , m 2 pieces of X 2 ' and m 2 pieces of X 2 ' ' are each independently a single bond, or -O -, - S -, - COO -, - OCONH- , represents -NHCO- or
-CONH-; m 2 pieces of R 4 and m 2 pieces of R 6 are each independently a hydrogen atom, an aliphatic hydrocarbon group having at least 5 carbon methyl group or a carbon; And
R 5 represents a number of 5 or more aliphatic hydrocarbon group having a carbon. ) Groups represented by;
　formula (c):
[0018]
[Formula 5]

[0019]
(Wherein,
* represents a bonding
position; m 3 is from 0 to an integer of
15; n 5 is an integer of 0 to
11; n 6 represents an integer of 0 to
5; m 3 number of X 3 is each independently a single bond, or -O -, - S -, - COO -, - OCONH -, - NHCO- or -CONH- indicates; and
m 3 groups of R 7 . are independently each hydrogen atom, a group represented by a methyl group or a 5 or more aliphatic hydrocarbon group having a carbon); or
　the formula (d):
[0020]
[Formula 6]

[0021]
(Wherein,
* represents a bonding
position; n 7 amino X 4 are each independently a single bond, or -O -, - S -, - COO -, - OCONH -, - NHCO - or shows a
-CONH-; R 8 represents a divalent aliphatic hydrocarbon
group; n 7 amino R 9 are each independently a monovalent aliphatic hydrocarbon
group; n 7 is 1 to an integer of 5; and
. Ar is a group represented by showing the arylene group)
is, [1] - benzyl compound according to any one of [4].
[6] R a has the formula (a) [wherein, m 1 is an 1; X 1 is either a single bond or -O- and is; R 1 and R 2 are independently each a divalent aliphatic hydrocarbon group having 5 to 80 carbon atoms; and R 3Is a hydrogen atom or formula (I ''):
[0022]
[Chemical Formula 7]

[0023]
(Wherein, * . Denotes the bonding position; Y is as defined for [1]) or formula (I '' '):
[0024]
[Formula 8]

[0025]
(Wherein * denotes the bonding position; Y is as defined for [1].) Is a group represented by. ; Group represented by]
the formula (b) (wherein, m 2 is an 1, n 1 , n 2 , n 3 and n 4 are each independently 0 or 1; X 2 , X 2 ' and X 2 ' ' are each independently a single bond, or -O- and is; R 4 and R 6 are independently each hydrogen atom, a methyl group or a C 5 to it is 80 aliphatic hydrocarbon group; and R 5 . is an aliphatic hydrocarbon group having 5 to 80 carbon groups represented by);
formula (c) (wherein, m 3 is from 1 to It is the integer 5; n 5 is an integer of
0-2; n 6Is an integer of 0 ~ 3; m 3 pieces of X 3 are both -O-; and, m 3 pieces of R 7 are aliphatic independently, several 5-80 carbon atoms hydrocarbons it is a hydrogen group. Or; group represented by)
the formula (d) (wherein, n 7 pieces of X 4 are both -O-; R 8 and n 7 amino R 9 are each independently, carbon atoms be 5-80 monovalent or divalent aliphatic hydrocarbon group; n 7 is an integer from 1 to 3;. and Ar is a group represented by phenylene)
is, [5] benzyl compounds described.
[7] R a has the formula (a) (wherein, m 1 is an 1; X 1 is -O-; R 1 and R 2 are each independently 8 carbon atoms to 60 an alkylene group; and R 3Is a hydrogen atom. ; Group represented by)
the formula (b) (wherein, m 2 is an 1, n 1 , n 2 , n 3 and n 4 are each located at 1, X 2 , X 2 ' and X 2 '' are both -O-; and R 4 , R 5 and R 6 are each independently an alkyl group having 8 to 60 carbon atoms group represented by);.
equation (c ) (wherein, m 3 is 2 or 3; n 5 is an 1; n 6 is 2 or 3; m 3 pieces of X 3 are both -O-; and , M 3 pieces of R 7They are each independently an alkyl group having 8 to 60 carbon atoms. Or; group represented by)
the formula (d) (wherein, n 7 pieces of X 4 are both -O-; R 8 is an alkylene group having 1 to 3 carbon atoms; n 7 pieces of R 9 are each independently an alkyl group having 8 to 60 carbon atoms; n 7 is an integer from 1 to 3; and Ar is a group represented by phenylene).
a, [5] benzyl compounds described.
[8] R a has the formula (a) (wherein, m 1 is an 1; X 1 is -O-; R 1 and R 2 are each independently having 14 to 30 carbon atoms an alkylene group; and R 3 .; is a hydrogen atom group represented by)
the formula (b) (wherein, m 2 is an 1, n 1 , n 2, N 3 and n 4 are each located at 1; X 2 , X 2 ' and X 2 ' ' are both -O-; and R 4 , R 5 and R 6 are each independently an alkyl group having 14 to 30 carbon atoms. ; Group represented by)
the formula (c) (wherein, m 3 is 2 or 3; n 5 is an 1, n 6 is an 3; m 3 pieces of X 3 are each is also -O-; and, m 3 pieces of R 7 are each independently an alkyl group having 14 to 30 carbon atoms group represented by);. or
formula (d) (in wherein, n 7 pieces of X 4 are both -O-; R 8 is an alkylene group having 1 to 3 carbon atoms; n 7 amino R 9 are each independently an alkyl group having 14 to 30 carbon atoms; n 7 is 2 or 3; and Ar it is a phenylene. ) The group represented by
is, [5] Benzyl compounds described.
[9] group OR a is present in the 2-position or 4-position on the benzene ring, [1] benzyl compound according to any one of to [8].
[10] groups R b is methoxy, [1] - benzyl compound according to any one of [9].
[11] Y is a hydroxyl group, [1] - benzyl compound according to any one of [10].
[12] Y is (wherein, R [1] are as defined herein.) -NHR group is, [1] benzyl compound according to any one of - [10].
[13] 4- (12' docosyloxy 1'-dodecyloxy) benzyl
alcohol; 4- (12' docosyloxy 1'dodecyloxy) -2-methoxybenzyl
alcohol; 4- (12' docosyloxy -1 '- dodecyloxy) -2-methoxy
benzylamine; 2- (12' docosyloxy 1'dodecyloxy) -4-methoxybenzyl alcohol;
2- (12' docosyloxy 1'dodecyloxy) -4-methoxy
benzylamine; 4-methoxy-2- [3 ', 4', 5'-tris (octadecyloxy) benzyl] benzyl
alcohol; 2- [3 ', 5'-di (docosyloxy) benzyloxy] -4-methoxy-benzyl
alcohol; 2-methoxy-4- [2', 2 ', 2'-tris (octadecyl oxymethyl) ethoxy] benzyl
alcohol; 2- methoxy-4- [2 ', 2', 2'-tris (octadecyl oxymethyl) ethoxy]
benzylamine; 4-methoxy-2- [3 ', 4', 5'-tris (octadecyloxy) cyclohexylmethyloxy] benzyl
alcohol; 4- [3 ', 4', 5'-tris (octadecyloxy) cyclohexylmethyl] benzyl alcohol;
, 22- bis [12- (4-hydroxymethyl-3-methoxyphenoxy) dodecyloxy] docosane; and
1,22- bis [12- (2-hydroxymethyl-5-methoxyphenoxy) dodecyloxy] docosanoic
group consisting It is selected from [11] or benzyl a compound according to any one of [12].
[14] 2-docosyloxy-4-methoxybenzyl
alcohol; 2-methoxy-4- [3 ', 4', 5'-tris (octadecyloxy) cyclohexylmethyl] benzyl alcohol;
3,5-dimethoxy-4- [3 ', 4', 5'-tris (octadecyloxy) cyclohexylmethyl] benzyl
alcohol; N-(4-hydroxymethyl-3-methoxyphenyl) -3,4,5 tris (octadecyl) cyclohexyl
carboxamide; N-(5-hydroxymethyl-2-methoxyphenyl) -3,4,5-tris (octadecyl) cyclohexyl carboxamide; and
N-(4-hydroxymethylphenyl) -3,4 , 5- tris (octadecyl) cyclohexyl carboxamide
is selected from the group consisting of, [11] or benzyl a compound according to any one of [12].
[15] [11] amino acid or peptide carboxyl protecting reagent consisting of benzyl compounds described.
[16] [11] C-terminal protecting reagent amino acid or a peptide consisting of benzyl compounds described.
[17] comprises the following steps, the production method of peptides by liquid phase synthesis method;
(1) [1] benzyl compound according to any one of to [14], the step of coupling an amino acid or peptide (binding step) , and
(2) above obtained in step, step (precipitation step) precipitating the coupling of an amino acid or peptide with benzyl compounds.
[18] comprising the steps of a method for manufacturing a peptide according to the liquid phase synthesis method;
(1) [1] - benzyl compound according to any one of [14], combined C-terminus and condensation of N- protected amino or N- protected peptide to give the C- protected amino or C- protected peptide step (C terminal protecting step),
(2) deprotection step of step (N-terminus to remove the protecting group of the N-terminus of the resulting amino acid or peptide in the above step),
(3) the resulting amino acid or peptide in the above step N the terminal, the step of condensing N- protected amino or N- protected peptide (peptide chain elongation step), and
(4) precipitating the peptide obtained in the above step (precipitation step).
Including [19] In addition the following step (5) to (7) repeating one or more of, [18] The method according peptide;
removing the protecting group of the N-terminus of (5) peptides obtained in the precipitation step step (deprotection step of N-terminal),
(6) the N-terminus of the peptide obtained in the above step, N- protected amino acid or N- protected peptide step condensation (peptide chain elongation step), and
(7) above precipitating the peptide obtained in step (precipitation step).
[20] After the precipitation step, C-protected further comprising the step of removing the C-terminal protecting group (anchor) of the peptide [18] or [19] The method according peptide.
[21] [1] The method for producing a peptide compound using benzyl compound according to any one of - [14].
[22] [1] The method for producing an organic compound using the benzyl compound according to any one of - [14].
[23] [1] -, characterized in that it is protected by a benzyl compound of any of [14], benzyl compound adducts.
[24] the following formula (III):
[0026]
[Formula 9]

[0027]
(Wherein, m 3 'represents an integer of 1 ~ 3; m 3 ' number of R 7 'are each independently an alkylene group having 14 to 30 carbon atoms, and Z' represents a hydroxyl group or a leaving, compounds represented by indicating the group.).
In [25] Formula (III), m 3 'is 3, and Z' is a hydroxyl group, a halogen atom, one or more alkyl sulfonyloxy group which may be substituted with a halogen atom, or optionally substituted it is an arylsulfonyl group, [24] the compound according.
The invention's effect
[0028]
　The use of specific benzyl compounds of the present invention as a protective reagent such as a carboxyl group, in organic synthesis reactions such as peptide synthesis, can carry out the reaction in homogeneous liquid phase, also by changing the solvent composition after the reaction single can only filtration and washed away and purified, while also suppressing the alkylation reaction in still acidic conditions during the deprotection, it is possible to obtain a product in high yield and high purity.
DESCRIPTION OF THE INVENTION
[0029]
　Unless defined otherwise, all technical and scientific terms used herein have the same meaning as the present invention is commonly understood by one of ordinary skill in the belonging art. Although any methods and materials similar or equivalent to those described herein, can be used in the practice or testing of the present invention, the preferred methods and materials are described below. All publications and patents mentioned herein, for example, are described in publications can be used in connection with the described invention, constructs and for the purpose of describing and disclosing the methodologies, hereby by reference It is incorporated in the book.
[0030]
　The present invention, certain benzyl compounds (hereinafter, abbreviated as the compound of the present invention) relates.
[Present compound]
　The compounds of the present invention, an organic synthesis reaction, preferably a peptide synthesis and the like, in, such as a carboxyl group, i.e., C-terminal, or the like of an amino acid or peptide, with a protective reagent to be introduced as a protecting group of (Anchor) There, suitable compounds of the present invention depending on the purpose may be selected.
[0031]
　The compounds are benzyl compound represented by the following formula (I).
[0032]
　Of formula (I):
[0033]
[Formula 10]

[0034]
Wherein,
Y represents a hydroxyl group or a group -NHR (R is a hydrogen atom, an alkyl group or an aralkyl group.);
R a represents an organic group having an aliphatic hydrocarbon group, the organic group the total number of carbons in There are 14 or more;
n number of R b are independently each C 1-6 alkoxy groups, optionally substituted halogen atom or with one or more halogen atoms, C 1-6 an alkyl group, R b each R when there are a plurality b or different are each identical; and
n is an integer of 0-4. Benzyl compounds represented by.
[0035]
　Compounds of the formula (I) of the present invention, through a Y group which bonds to compounds intended for protected.
　That, Y is hydroxyl group or a compound of the invention which is -NHR group, is protected in combination with the C-terminus of the amino acid or peptide or the like.
[0036]
　In the present specification, the "alkyl group" represented by R, C 1-30 include alkyl groups, preferably C 1-10 alkyl groups, more preferably C 1-6 alkyl group. Preferable specific examples include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec- butyl, tert- butyl and the like, especially methyl, ethyl is preferred.
[0037]
　In the present specification, the "aralkyl group" represented by R, C 7-30 an aralkyl group, preferably a C 7-20 aralkyl group, more preferably C 7-16 aralkyl group (C 6-10 aryl -C 1-6 alkyl group). Suitable examples include benzyl, 1-phenylethyl, 2-phenylethyl, 1-phenylpropyl, naphthylmethyl, 1-naphthylethyl, 1-naphthyl-propyl, and the like, especially benzyl is preferred.
[0038]
　As R, a hydrogen atom, C 1-6 alkyl group or a C 7-16 aralkyl group are preferable, a hydrogen atom, methyl, more preferably ethyl or benzyl, particularly preferably a hydrogen atom.
[0039]
　Herein, R a as an "organic group having an aliphatic hydrocarbon group" represented a monovalent organic group having an aliphatic hydrocarbon group in the molecular structure.
[0040]
　The "aliphatic hydrocarbon group" of the "organic group having an aliphatic hydrocarbon group" is a linear or branched, saturated or unsaturated aliphatic hydrocarbon group, having 5 or more aliphatic carbon hydrocarbons preferably a hydrogen radical, particularly preferably an aliphatic hydrocarbon group having 5 to 60 carbon atoms, more preferably an aliphatic hydrocarbon group having 5 to 30 carbon atoms, more preferably an aliphatic hydrocarbon group having 10 to 30 carbon atoms.
　Site of "aliphatic hydrocarbon group" of the "organic group having an aliphatic hydrocarbon group" is not particularly limited, (monovalent groups) be present in the end, it may be present in the other portion (for example divalent group).
[0041]
　As the "aliphatic hydrocarbon group", the alkyl group, cycloalkyl group, alkenyl group, cycloalkenyl group, include monovalent and divalent groups derived therefrom, such as an alkynyl group, preferably a methyl group, an ethyl group, a propyl group, an isopropyl group, butyl group, isobutyl group, sec- butyl group, tert- butyl group, a pentyl group, a hexyl group, an octyl group, a decyl group, dodecyl group, lauryl group, tridecyl group, myristyl group, cetyl group, stearyl group, arachidyl group, behenyl group, oleyl group, and a monovalent group and a divalent group derived therefrom, such as isostearyl group.
[0042]
　Sites other than the "aliphatic hydrocarbon group" in the "organic group having an aliphatic hydrocarbon group" can be set arbitrarily. For example, -O as a linker -, - S -, - COO -, - OCONH-, and -CONH-, and, sites may have such hydrocarbon group (monovalent or divalent). As the "hydrocarbon group", for example, aliphatic hydrocarbon groups, aromatic aliphatic hydrocarbon group, monocyclic saturated hydrocarbon group and an aromatic hydrocarbon group and the like, specifically, for example, an alkyl group , an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group, monovalent groups and divalent groups derived from these, such as an aralkyl group is used. As the "alkyl group", for example, C 1-6 alkyl group and the like are preferable, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec- butyl, tert- butyl, pentyl, hexyl and the like. As the "alkenyl group", for example, C 2-6 alkenyl groups are preferable, for example, vinyl, 1-propenyl, allyl, isopropenyl, butenyl, isobutenyl, and the like. As the "alkynyl group", for example, C 2-6 alkynyl group, etc. are preferable, for example, ethynyl, propargyl, 1-propynyl, and the like. As the "cycloalkyl group", for example, C 3-6 preferably a cycloalkyl group such as, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl. "Aryl group", for example, C 6-14 aryl group and the like are preferable, for example, phenyl, 1-naphthyl, 2-naphthyl, biphenylyl, 2-anthryl and the like. Among them, C 6-10 more preferably an aryl group, and particularly preferably phenyl. The "aralkyl group", for example, C 7-20 preferably an aralkyl group such as benzyl, 1-phenylethyl, 2-phenylethyl, 1-phenylpropyl, naphthylmethyl, 1-naphthylethyl, 1-naphthyl-propyl, etc. and the like. Among them, C 7-16 aralkyl group (C 6-10 aryl -C 1-6 alkyl group) is more preferable, benzyl is especially preferred. The "hydrocarbon group", halogen atom (chlorine atom, bromine atom, fluorine atom, iodine atom), one or more carbon atoms which may be substituted by a halogen atom 1-6 alkyl group, oxo group it may be substituted with a substituent selected.
[0043]
　The compounds of the present invention, one of OR a having a group. Here, OR a "organic group having an aliphatic hydrocarbon group" constituting the base, a plurality of "aliphatic hydrocarbon group" may be present such as by branch. If the "aliphatic hydrocarbon group" in the "organic group having an aliphatic hydrocarbon group" there are a plurality, each of which may be different even the same.
[0044]
　OR a group, from the viewpoint of the final de-anchor is facilitated, it is preferable to bind the 2-position or 4-position on the benzene ring of the compound of the present invention, but are not limited thereto.
[0045]
　In the present invention compounds, R a in the "organic group having an aliphatic hydrocarbon group" represented as the lower limit is preferably 14 or more total carbon atoms, more preferably 16 or more, more preferably 20 or more, 24 or more even more preferably, especially preferably 30 or more. On the other hand, R a in the "organic group having an aliphatic hydrocarbon group" represented as the upper limit of the total number of carbon atoms is preferably 200 or less, more preferably 150 or less, more preferably 120 or less, still more preferably 100 or less , especially preferably 80 or less, particularly preferably 60 or less. As the number of carbon atoms is large, the peptide chain crystallinity is improved in a polar organic solvent, even the present compounds when a long chain.
[0046]
　R a as "organic group having an aliphatic hydrocarbon group" represented as include any of the group selected for example from the following formulas (a) ~ (d).
[0047]
　Formula (a):
[0048]
[Of 11]

[0049]
Wherein
(a), * represents a bonding
position; m 1 represents an integer of 1 ~
10; m 1 pieces of X 1 are each independently a single bond, or -O-, -S -, - COO -, - OCONH -, - NHCO- or shown
-CONH-; R 1 and m 1 pieces of R 2 is, independently each having 5 or more divalent carbon aliphatic hydrocarbons It represents a group; and
R 3 is a hydrogen atom or the formula, (I '):
[0050]
[Chem. 12]

[0051]
(Wherein, * represents a binding position, and the other symbols. Indicating the same meaning) shows a. A group represented by.
[0052]
　R 1 or R 2 as "aliphatic hydrocarbon group having 5 or more carbon atoms" represented by, among "aliphatic hydrocarbon group" of the "organic group having an aliphatic hydrocarbon group" described above, the number of carbon atoms 5 include those described above, preferably carbon atoms 5-80.
[0053]
　In formula
(a), m 1 is located at
1; X 1 is either a single bond or -O- and
is; R 1 and R 2 are each independently 2 having 5 to 80 carbon atoms It is valent aliphatic hydrocarbon group; and
R 3 is a hydrogen atom or a formula (I ''):
[0054]
[Formula 13]

[0055]
(Wherein, * . And Y are as defined above) or formula (I '' '):
[0056]
[Formula 14]

[0057]
(Wherein, * . And Y are as defined above) is, groups are preferred, inter
alia, m 1 is located at
1; X 1 is a
-O-; R 1 and R 2 are independently each is alkylene group having 8 to 60 carbon atoms; and
R 3 is a hydrogen atom, group is more preferable.
[0058]
　In particular groups of preferred formula (a)
is, m 1 is located at
1; X 1 is a
-O-; R 1 and R 2 are each independently an alkylene group having 14 to 30 carbon atoms There; and
R 3 is a hydrogen atom, a group.
[0059]
　Of formula (b):
[0060]
[Formula 15]

[0061]
(In the formula
(b), * represents a bonding
position; m 2 represents 1 or
2; n 1 , n 2 , n 3 and n 4 are each independently an integer of 0 to 2;
m 2 pieces of X 2 , m 2 pieces of X 2 ' and m 2 pieces of X 2 ' ' are each independently a single bond, or -O -, - S -, - COO -, - OCONH -, - NHCO- or -CONH-
indicates; m 2 pieces of R 4 and m 2 pieces of R 6 are each independently a hydrogen atom, a methyl group or an aliphatic hydrocarbon group having 5 or more carbon atoms shows;
R 5 represents a number of 5 or more aliphatic hydrocarbon group having a carbon. ) Is a group represented by.
[0062]
　R 4 , R 5 or R 6 as "5 or more aliphatic hydrocarbon group having a carbon" represented by, among "aliphatic hydrocarbon group" of the "organic group having an aliphatic hydrocarbon group" described above, carbon number include 5 or more of, preferably 5 to 80 carbon atoms.
[0063]
　In formula
(b), m 2 is located at
1; n 1 , n 2 , n 3 and n 4 are each independently 0 or
1; X 2 , X 2 'and X 2 ' 'is , each independently a single bond, or -O- and is;
R 4 and R 6 are each independently a hydrogen atom, an aliphatic hydrocarbon group of a methyl group or a carbon number of 5-80 ; and
R 5 is an aliphatic hydrocarbon group having 5 to 80 carbon atoms, groups are preferred, inter
alia, m 2 is located at
1, n 1 , n 2 , n 3 and n 4 are both located in
1; X 2 , X 2 'and X 2 are' ', both are
-O-; R 4 , R 5 , and R 6 are each independently 8 carbon atoms 60 alkyl group, group is more preferable.
[0064]
　In particular groups of preferred formula (b)
is, m 2 is located at
1; n 1 , n 2 , n 3 and n 4 are both located in
1; X 2 , X 2 'and X 2 are' both are
-O-; R 4 , R 5 and R 6 are each independently an alkyl group having 14 to 30 carbon atoms, a group.
[0065]
　Of formula (c):
[0066]
[Chemical Formula 16]

[0067]
(Wherein,
* indicates the bonding
position; m 3 is from 0 to an integer of
15; n 5 is an integer of 0 to
11; n 6 is 0 to an integer of
5; m 3 or X of 3 are each independently a single bond, or -O -, - S -, - COO -, - OCONH -, - NHCO- or -CONH-
indicates; m 3 pieces of R 7 is each, independently, a hydrogen atom, a group represented by a methyl group or a 5 or more aliphatic hydrocarbon group having a carbon.).
[0068]
　R 7 as "5 or more aliphatic hydrocarbon group having a carbon" represented by, among "aliphatic hydrocarbon group" of the "organic group having an aliphatic hydrocarbon group" described above, having a carbon number of 5 or more and the like, preferably 5 to 80 carbon atoms.
[0069]
　In formula
(c), m 3 is an integer of 1 -
5; n 5 is 0-2
integer; n 6 is 0 to be the integer
3; m 3 pieces of X 3 is, both are -O-; and
m 3 pieces of R 7 are each independently an aliphatic hydrocarbon group having 5 to 80 carbon atoms, groups are preferred, inter
alia, m 3 is 2 or 3
There; n 5 is located at
1; n 6 is located at 2 or
3; m 3 pieces of X 3 are both a -O-; and
m 3 amino R 7But independently, an aliphatic hydrocarbon group having 8 to 60 carbon atoms, group is more preferable.
[0070]
　In particular groups of preferred formula (c) it
is, m 3 is located at the 2 or
3; n 5 is located at
1; n 6 is located at
3; m 3 pieces of X 3 are both -O- in it; and
m 3 pieces of R 7 are each independently an alkyl group having 14 to 30 carbon atoms, a group.
[0071]
　Formula (d):
[0072]
[Chemical Formula 17]

[0073]
(In the formula
(d), * represents a bonding
position; n 7 amino X 4 is either a single bond or -O -, - S -, - COO -, - OCONH -, - NHCO- or - indicates
CONH-; R 8 represents a divalent aliphatic hydrocarbon
group; n 7 amino R 9 is a monovalent aliphatic hydrocarbon
group; n 7 represents an integer of 1 to 5 ; and
Ar is a group represented by an arylene group)..
[0074]
　R 8 or R 9 indicated by "aliphatic hydrocarbon group" include those similar to the "aliphatic hydrocarbon group" of the "organic group having an aliphatic hydrocarbon group" described above. Preferably 5 or more carbon atoms, more preferably from 5 to 80 carbon atoms, and particularly preferably 8 to 60.
[0075]
　As "arylene group" represented by Ar, for example, phenylene, naphthylene, biphenylene, and the like, preferably phenylene.
[0076]
　In the formula
(d), n 7 pieces of X 4 are both a
-O-; R 8 and n 7 amino R 9 is a monovalent or divalent separate carbon atoms respectively 8 to 60 aliphatic be a family hydrocarbon
group; n 7 is an integer from 1 to 3; and
Ar is a phenylene, group is preferable, among
others, n 7 pieces of X 4 are both a
-O-; R 8 is an alkylene group having 1 to 3 carbon
atoms; n 7 amino R 9 are each independently an alkyl group having 14 to 30 carbon
atoms, n 7 is located at 2 or 3; and
Ar There is a phenylene, group is more preferable.
[0077]
　In particular groups of preferred formula (d) it
is, n 7 pieces of X 4 are both a
-O-; R 8 is, be a methylene
group; n 7 amino R 9 each, independently, carbon an alkyl group having 14 ~
30, n 7 is located at 2 or 3; and
Ar is phenylene, a group.
[0078]
　Specific examples of the "organic group having an aliphatic hydrocarbon group" include groups having the following aliphatic carbon chain having a carbon number of 18-100. In each group * represents a bonding position.
[0079]
[Chem. 18]

[0080]
　As used herein, "R b Specific preferable examples of the group", C 1-6 alkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec- butoxy, C etc. tert- butoxy 1-4 alkoxy group), one or more a C substituted with halogen 1-6 alkyl group (e.g., methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec- butyl, tert- butyl, pentyl, C of hexyl 1-6 alkyl group, trifluoromethyl, halogen-substituted C trichloromethyl like 1-6 alkyl group), or a halogen atom. Among them C 1-6 alkoxy group (particularly methoxy group) preferable. Benzyl compounds of the present invention, preferably, the "R on the benzene ring b or not have a group", or, C 1-6 having an alkoxy group. "R b group" of n exist in total (the n is an integer of 0 to 4.), Preferably from 0 to 2, more preferably 0 or 1.
[0081]
　Preferred examples of the present invention benzyl compounds include the following benzyl compounds.
[0082]
　4- (12'-docosyloxy-1'-dodecyloxy) benzyl
alcohol; 4- (12' docosyloxy 1'dodecyloxy) -2-methoxybenzyl
alcohol; 4- (12' docosyloxy-1'-dodecyl oxy) -2-methoxy
benzylamine; 2- (12' docosyloxy 1'dodecyloxy) -4-methoxybenzyl
alcohol; 2- (12' docosyloxy 1'dodecyloxy) -4-methoxybenzylamine ;
2-docosyloxy-4-methoxybenzyl
alcohol; 4-methoxy-2- [3 ', 4', 5'-tris (octadecyloxy) benzyloxy) benzyl
alcohol; 2- [3 ', 5'-di (docosyloxy ) benzyloxy] -4-methoxy-benzyl
alcohol; 2-methoxy-4- [2 ', 2', 2' Squirrel (octadecyl oxymethyl) ethoxy) benzyl
alcohol; 2-methoxy-4- [2 ', 2', 2'-tris (octadecyl oxymethyl) ethoxy] benzylamine;
4-methoxy-2- [3 ', 4' , 5'-tris (octadecyloxy) cyclohexylmethyl] benzyl
alcohol; 2-methoxy-4- [3 ', 4', 5'-tris (octadecyloxy) cyclohexylmethyl] benzyl
alcohol; 4- [3 ', 4 ', 5'-tris (octadecyloxy) cyclohexylmethyl] benzyl alcohol;
3,5-dimethoxy-4- [3 ', 4', 5'-tris (octadecyloxy) cyclohexylmethyl] benzyl
alcohol; N-(4-hydroxymethyl-3-methoxyphenyl) -3,4,5 tris (octadecyl) cyclohexyl
carboxamide; N-(5-hydroxymethyl-2-methoxyphenyl) -3,4,5-tris (octadecyl) cyclohexyl
carboxamide; N-(4-hydroxymethylphenyl) -3,4, 5- tris (octadecyl) cyclohexyl
carboxamide; 1,22- bis [12- (4-hydroxymethyl-3-methoxyphenoxy) dodecyloxy] docosanoic; or
1,22- bis [12- (2-hydroxy-5 - methoxyphenoxy) dodecyloxy] docosane.
[0083]
Manufacturing method of the present invention compounds]
　The production method of the present invention compound is not particularly limited, can be synthesized, for example, through the following reaction.
　Starting compound, unless otherwise stated, either readily available commercially or can be prepared according to methods analogous to methods known per se or to them.
　The following may vary depending yield using the reaction conditions of the compound obtained in the way, but conventional means from these products (recrystallization, column chromatography and the like) and isolated and purified by, then change the solution temperature it can be precipitated by means such as varying the means or solution composition for.
　Moreover, in each reaction, the starting compound has a hydroxyl group, an amino group, a carboxyl group, if having a carbonyl group or the like, may be protective group generally used in peptide chemistry or the like to these groups have been introduced, it is possible to obtain the desired compound by removing the protecting group as necessary after the reaction.
[0084]
　The compound of the present invention, for example, can be produced by the following steps.
[0085]
[Of 19]

[0086]
[R in the formula 'is a hydrogen atom or OR' (wherein, R '' group 'is C 1-6 alkyl group such as an alkyl group,. Showing an aralkyl groups such as benzyl group) a, R' ' 'is an alkyl group or an aralkyl group, Z is a leaving group such as a halogen atom, the other symbols have the same meanings as defined above. ]
[0087]
Step (a)
　the process is a compound represented by the formula (II) (hereinafter, compound (II) and abbreviated.) Group R to a hydroxyl group of a by introducing, represented by formula (IIa) compound (hereinafter, abbreviated as compound (IIa).) is a step for preparing a.
　The reaction is carried out in a solvent which does not affect the reaction in the presence of a base, group R a halide corresponding to (chloride, bromide or iodide), or a group R a alkylsulfonyloxy compound corresponding to (e.g. , methanesulfonyloxy compound, etc.) or arylsulfonyloxy halide (e.g., p- toluenesulfonyloxy products, etc.) or is performed using, or the group R the compound (II) a triphenyl phosphine and azo an alcohol corresponding to the It carried out under Mitsunobu reaction conditions to react under diisopropyl dicarboxylic acid present.
[0088]
　As the base, for example, sodium carbonate, sodium hydrogen carbonate, potassium carbonate, sodium hydride, alkali metal salts such as potassium hydride, potassium tert- butoxide; pyridine, triethylamine, N, N-dimethylaniline, 1,8-diazabicyclo [5.4.0] organic bases such as undec-7-ene. of these, sodium carbonate, potassium carbonate, sodium hydride and the like are preferable.
[0089]
　As the solvent, for example, toluene, xylene and the like aromatic hydrocarbons; ethers such as tetrahydrofuran and dioxane; dimethylformamide, amides such as dimethylacetamide; chloroform, halogenated hydrocarbons such as dichloromethane; nitriles such as acetonitrile s like, or mixtures thereof, among others, dimethyl formamide, tetrahydrofuran, toluene, N- methylpyrrolidone is preferred.
[0090]
　The reaction temperature is usually 50 ° C. ~ 0.99 ° C., preferably from 60 ℃ ~ 130 ℃. The reaction time is usually 2 to 30 hours, preferably 3-10 hours.
[0091]
Step (b)
　the process is by reducing the compound (IIa), a compound represented by formula (I-a) (hereinafter, abbreviated as Compound (I-a).) Is a step for preparing a. The reduction reaction can be carried out by a method using a reducing agent.
[0092]
　The reducing agent used in the reduction reaction, for example, a metal hydride (sodium borohydride, lithium borohydride, sodium cyanoborohydride, sodium triacetoxyborohydride, hydride dibutyl aluminum hydride, aluminum hydride, It includes lithium aluminum etc.), and among them, sodium borohydride, dibutyl aluminum are preferred.
[0093]
　The reaction is carried out in a solvent which does not affect the reaction. As the solvent, for example, alcohols such as methanol and ethanol; ethers, such as diethyl ether, tetrahydrofuran, and dioxane; toluene, aromatic hydrocarbons such as xylene; or a mixture thereof. Among these tetrahydrofuran, toluene, etc. It is preferred.
[0094]
　The reaction temperature is usually in 0 ° C. ~ 100 ° C., preferably from 30 ° C. ~ 70 ° C., the reaction time is usually 1 to 24 hours, preferably 2-5 hours.
[0095]
Step (c-1)
　the process is (wherein (IIa), R 'is a hydrogen atom) Compound (IIa) and by oximation of formula (I'-a) a compound represented by ( hereinafter referred to as compound (I'-a).) is a step for preparing a.
　The oximation reaction is carried out in a solvent which does not affect the reaction, carried out by a compound in the presence of a base and (IIa) is reacted with a hydroxylamine acid addition salt.
[0096]
　The acid addition salt of hydroxylamine, for example, hydrochloride, sulfate, nitrate and the like mineral, acetate, trifluoroacetate, methanesulfonate, trifluoromethanesulfonate, p- toluenesulfonate, etc. It includes organic acids salts of, but hydrochlorides being especially preferred.
[0097]
　Examples of the base include potassium hydroxide, sodium hydroxide, sodium hydrogen carbonate, alkali metal salts such as potassium carbonate; pyridine, triethylamine, diisopropylethylamine, N, N-dimethylaniline, 1,8-diazabicyclo [5.4 .0] organic bases such as such as undec-7-ene, among which triethylamine, diisopropylethylamine and the like are preferable.
[0098]
　As the solvent, for example, chloroform, a solvent such as dichloromethane: toluene, xylene and the like aromatic hydrocarbons; ethers such as tetrahydrofuran and dioxane; and / or mixtures thereof. Among them, dichloromethane, chloroform, toluene, and the like are preferable.
[0099]
　The reaction temperature is generally 10 ° C. ~ 100 ° C., preferably from 20 ° C. ~ 60 ° C., the reaction time is usually from 0.5 to 30 hours, preferably 2 to 20 hours.
[0100]
Step (c-2)
　the process is a compound (I'-a), palladium - carbon, the presence of a metal catalyst such as Raney nickel, catalytic hydrogenation, or the step (b) the same, such as a metal hydride by reduced by a reducing agent, to produce formula is present compound (I-b) a compound represented by (hereinafter referred to as compound (I-b).).
[0101]
　Compound (I-b) can also be prepared through the step (c-3) step a (c-4) and the step (c-5).
[0102]
Step (c-3)
　the process is the compound (I-a) for example, acetyl chloride, chlorinated agent such as thionyl chloride or, for example, acetyl bromide, phosphorus tribromide, bromination, such as diphenyl phosphine / bromine by halogenating with agent, the compound represented by formula (I'-b) (hereinafter, abbreviated as compound (I'-b).) is a step for preparing a.
[0103]
　As the solvent, for example, chloroform, halogenated hydrocarbons such as dichloromethane; toluene, aromatic hydrocarbons such as xylene; ethers such as tetrahydrofuran and dioxane; mixtures thereof. Among them, chloroform, tetrahydrofuran, toluene etc. are preferred.
[0104]
　The reaction temperature is generally 10 ° C. ~ 0.99 ° C., preferably from 30 ° C. ~ 80 ° C., the reaction time is usually from 0.5 to 30 hours, preferably 2 to 20 hours.
[0105]
Step (c-4)
　the process is by azide using the compound (I'-b) the azide agent such as sodium azide, the compound represented by formula (I'-c) (hereinafter, abbreviated as compound (I'-c).) is a step for preparing a.
　The reaction is carried out in a solvent which does not affect the reaction, the compound (I'-b) carried out by reacting with an azide agent.
[0106]
　As the solvent, for example, chloroform, halogenated hydrocarbons such as dichloromethane; toluene, aromatic hydrocarbons such as xylene; ethers such as tetrahydrofuran and dioxane; N, N-amides such as dimethylformamide; mixtures thereof . Among them, chloroform, N, N-dimethylformamide, etc. are preferable.
[0107]
　The reaction temperature is generally 10 ° C. ~ 0.99 ° C., preferably from 20 ° C. ~ 100 ° C., the reaction time is usually from 0.5 to 30 hours, preferably 2 to 20 hours.
[0108]
Step (c-5)
　the process is by amination of compound (I'-c), a step for preparing a compound (I-b).
　The reaction is carried out in a solvent which does not affect the reaction, presence of water, or to the compound (I'-c) is reacted with triphenylphosphine is carried out by catalytic hydrogenation reduction.
[0109]
　The amount of triphenylphosphine relative to the compound (I'-c) 1 mol, preferably 1 to 10 mol, particularly preferably 1 to 5 mol.
[0110]
　The amount of water used relative to the compound (I'-c) 1 mol, preferably 1 to 10 mol, particularly preferably 1 to 5 mol.
[0111]
　As the solvent, for example, toluene, xylene and the like aromatic hydrocarbons; ethers such as tetrahydrofuran and dioxane; and mixtures thereof. Among them, toluene, tetrahydrofuran and the like are preferable.
[0112]
　The reaction temperature is generally 10 ~ 0.99 ° C., preferably 20 ~ 100 ° C., the reaction time is usually from 0.5 to 30 hours, preferably 2 to 20 hours.
[0113]
Step (c-6)
　the process is the compound (I'-b) R '' 'NH 2 By (R' '' has the same meaning as defined above) is reacted with, Y in the compound of the present invention is -NHR '' 'is a group, the compounds represented by formula (I-c) (hereinafter, abbreviated as compound (I-c).) is a step for preparing a.
　The reaction is carried out in a solvent which does not affect the reaction, if necessary, for example, triethylamine, in the presence of a base such as a tertiary amine, such as diisopropylethylamine, compound (I'-b) the R '' '- NH 2 It is carried out by reacting with in represented by amines.
[0114]
　As the solvent, for example, toluene, xylene and the like aromatic hydrocarbons; ethers such as tetrahydrofuran and dioxane; and chloroform, halogenated hydrocarbons such as dichloromethane, or mixtures thereof. Among these, toluene , tetrahydrofuran, chloroform, etc. are preferable.
[0115]
　The reaction temperature is generally 10 ~ 100 ° C., preferably 20 ~ 60 ° C., the reaction time is usually from 0.5 to 30 hours, preferably 2 to 20 hours.
[0116]
　Incidentally, the group R was used as the starting compound a halide corresponding to are either commercially available, or, for example, the following steps (d-1), (d -2), (e), ( f), can be prepared by (g), or their analogous methods.
[0117]
Project (d-1)
[0118]
[Of 20]

[0119]
[In the above scheme, Hal is halogen atom; indicates (chlorine atom, bromine atom, iodine atom, fluorine atom preferably bromine atom or iodine atom), R 1 and R 2 are as defined above. ]
[0120]
　Per 1 mol of compound (1), to give compound 1-5 mole of the compound (2) compound is reacted with a (3). In this step, the presence of a base in a solvent that does not adversely influence the reaction.
[0121]
　Examples of the base include potassium hydroxide, sodium hydroxide, sodium hydrogen carbonate, alkali metal salts such as potassium carbonate; pyridine, triethylamine, N, N-dimethylaniline, 1,8-diazabicyclo [5.4.0] organic bases such as undec-7-ene; potassium hydride, metal hydrides such as sodium hydride; sodium methoxide, sodium ethoxide, and alkali metal alkoxides such as potassium tert- butoxide.
[0122]
　Examples of the solvent, chloroform, halogenated hydrocarbons such as dichloromethane; 1,4-dioxane, nonpolar organic solvents such as tetrahydrofuran. These solvents may be used in a mixture at an appropriate ratio. Preferably tetrahydrofuran.
[0123]
　The reaction temperature is generally 20 ° C. ~ 0.99 ° C., preferably from 50 ℃ ~ 100 ℃. The reaction time is usually 1 to 30 hours.
[0124]
Project (d-2)
[0125]
[Of 21]

[0126]
(Wherein each symbol is as defined above.)
[0127]
　Compound (5) with respect to 1 mol, to obtain a compound (6) Compound (4) by 0.3 to 5 mol reaction. This process comprises the steps presence of the same base and (d-1), carried out in a solvent that does not adversely influence the reaction. R a is a group which is represented by formula (a), R in formula (a) 3 compound is the formula (I ') (I), relative to 1 mol of the compound (II), compound after the (6) was 0.5 to 5 mol reaction, it can be synthesized via reduction step.
[0128]
Engineering (e)
[0129]
[Formula 22]

[0130]
(Each group in the formula has the same meaning as defined above.)
[0131]
　Compound (7) with respect to 1 mol of reacted 0.2-5 moles of compound (8) to give compound (9), compound by substituting the hydroxyl group of compound (9) halogen (10) it is a process to obtain. In the reaction of the compound (7) with the compound (8), the presence of a base in a solvent that does not adversely influence the reaction.
[0132]
　Examples of the base include potassium hydroxide, sodium hydroxide, sodium hydrogen carbonate, alkali metal salts such as potassium carbonate; pyridine, triethylamine, N, N-dimethylaniline, 1,8-diazabicyclo [5.4.0] organic bases such as undec-7-ene; potassium hydride, metal hydrides such as sodium hydride; sodium methoxide, sodium ethoxide, and alkali metal alkoxides such as potassium tert- butoxide.
[0133]
　Examples of the solvent include benzene, toluene, aromatic hydrocarbons such as xylene; acetonitrile, nitriles such as propionitrile; tetrahydrofuran, 1,4-dioxane, ethers such as diethyl ether; acetone, 2-butanone ketones such as: chloroform, halogenated hydrocarbons such as dichloromethane; N, N-amides such as dimethylformamide; and sulfoxides such as dimethyl sulfoxide. These solvents may be used in a mixture at an appropriate ratio. Preferably dimethylformamide. The amount of the solvent to be used, relative to compound (7), 2 to 50 fold volume are preferred.
[0134]
　The reaction temperature is generally 20 ° C. ~ 0.99 ° C., preferably from 50 ℃ ~ 100 ℃. The reaction time is usually 1 to 30 hours.
[0135]
　Compound hydroxyl groups (9) substituted with halogen, to give compound (10), in a solvent which does not adversely influence the reaction, the compound (9), be carried out by reacting triphenylphosphine and a halogen source can. This step is preferably carried out in the presence of imidazole. Carbon tetrachloride as a halogen source, hexachloroacetone and triphosgene (chlorine source), carbon tetrabromide (source of bromine) include iodomethane and iodine (iodine) and the like. The amount of triphenylphosphine, the compound (9) relative to 1 mol, preferably 0.1 to 5 moles, the amount of the halogen source is, the compound (9), relative to 1 mol is preferably 1 to 5 moles . The amount used in the case of using the imidazole compound (9) relative to 1 mol, preferably 0.1 to 5 mol.
[0136]
　Examples of the solvent include benzene, toluene, aromatic hydrocarbons such as xylene; acetonitrile, nitriles such as propionitrile; tetrahydrofuran, 1,4-dioxane, ethers such as diethyl ether; acetone, 2-butanone ketones such as: chloroform, halogenated hydrocarbons such as dichloromethane; N, N-amides such as dimethylformamide; and sulfoxides such as dimethyl sulfoxide. These solvents may be used in a mixture at an appropriate ratio. Preferably is toluene. The amount of the solvent to be used, relative to compound (9), preferably 3 to 50 times volume.
[0137]
　The reaction temperature is generally 30 ° C. ~ 0.99 ° C., preferably from 40 ℃ ~ 120 ℃. The reaction time is usually 0.5 to 24 hours.
[0138]
Project (f)
[0139]
[Of 23]

[0140]
(Each group in the formula has the same meaning as defined above.)
[0141]
　Compound (11) with respect to 1 mole, 1 to 5 moles of acetyl chloride, chlorinated agent such as thionyl chloride, acetyl bromide, phosphorus tribromide, a halogenating agent brominating agent such as diphenyl phosphine / bromine It reacted to give compound compound (12). This reaction is carried out in a solvent which does not adversely influence the reaction.
[0142]
　Examples of the solvent, for example, chloroform, halogenated hydrocarbons such as dichloromethane; benzene, toluene, aromatic hydrocarbons such as xylene; 1,4-dioxane, ethers such as diethyl ether; and the like. These solvents may be used in a mixture at an appropriate ratio. Preferably chloroform or N, N- dimethylformamide. The amount of the solvent to be used, relative to compound (11), 2 to 50 fold volume are preferred.
[0143]
　The reaction temperature is usually 0 ° C. ~ 100 ° C., preferably from 0 ℃ ~ 30 ℃. The reaction time is usually 0.5 to 30 hours.
[0144]
Project (g)
[0145]
[Of 24]

[0146]
(Wherein, Z 'represents a hydroxyl group or a leaving group,, m 3 ' is 1-3, preferably an 3 R 7 'is as defined above.)
[0147]
　Relative to the compound (13), rhodium - obtain a carbon (Rh / C) catalyst by catalytic hydrogenation reacted with compounds such as (14), and further reduction of the ester moiety of compound (14), Z 'is a hydroxyl group a step of obtaining a compound of (III). The process is a halogen group from a hydroxyl group, one or more optionally substituted alkylsulfonyloxy group with a halogen atom (e.g., such as methanesulfonyloxy group), an optionally substituted arylsulfonyloxy group (e.g., p - also includes obtaining compound Z 'is a leaving group by conversion to toluenesulfonyloxy group, etc.) or the like (III). This reaction is carried out in a solvent which does not adversely influence the reaction.
[0148]
　"One or more of alkyl sulfonyloxy group which may be substituted by halogen atom", "alkyl" or "aryl" of the "arylsulfonyl group" is a group as defined above, "optionally substituted "substituent" of the arylsulfonyloxy group ", halogen atom, one or more alkyl groups of having 1 carbon atoms which may 6 be substituted by a halogen atom, an an alkoxy group having 1 to 6 carbon atoms.
[0149]
　The reducing agent used in the reduction reaction, for example, a metal hydride (sodium borohydride, lithium borohydride, sodium cyanoborohydride, sodium triacetoxyborohydride, hydride dibutyl aluminum hydride, aluminum hydride, lithium aluminum and the like) and the like. Among them, hydrogenated dibutyl aluminum are preferred.
[0150]
　The reaction is carried out in a solvent which does not affect the reaction. As the solvent, for example, alcohols such as methanol and ethanol; ethers, such as diethyl ether, tetrahydrofuran, and dioxane; toluene, aromatic hydrocarbons such as xylene; or a mixture thereof. Among these tetrahydrofuran, toluene, etc. It is preferred.
[0151]
　The reaction temperature is usually -10 ° C. ~ 100 ° C., preferably from 0 ° C. ~ 70 ° C., the reaction time is usually 1-24 hours, preferably 2-5 hours.
[0152]
　The Reagents used for conversion to a leaving group, for example, chlorinated agents exemplified above step (f), other brominated agent, methanesulfonyl chloride, alkylsulfonyl agent such as trifluoromethanesulfonyl chloride, benzene chloride sulfonyl, such as arylsulfonyl agent such as chloride p- toluenesulfonyl, and among them, arylsulfonyl agent is preferred.
[0153]
　The reaction is carried out in a solvent inert to the reaction, the solvent, such as chloroform, halogenated hydrocarbons such as dichloromethane; an aromatic hydrocarbon such as benzene, toluene and xylene; acetonitrile, propionitrile nitriles such as nitrile; tetrahydrofuran, 1,4-dioxane, ethers such as diethyl ether, and among them halogenated hydrocarbons such as chloroform are preferred.
[0154]
　The reaction is preferably compound (15) with respect to 1 mol of an organic base such as 1 to 5 mol of pyridine, and 0.05-0.8 moles of N, N-dimethyl-4-aminopyridine catalyst It is carried out under coexistence.
[0155]
　The reaction temperature is usually 0 ° C. ~ 100 ° C., preferably from 0 ° C. ~ 70 ° C., the reaction time is usually 1-24 hours, preferably 2-5 hours.
[0156]
　Step (d-1), (d-2), a (e), (f), and the compound obtained in (g) (3), (6), (10), (12) and (16) used, by carrying out the reaction of the above-mentioned step (a), can be obtained for preparing the compounds of this invention, it is a useful intermediate compound (IIa). Incidentally, in the scheme, the carbon number and type of halogen atoms of the aliphatic hydrocarbon group, the reaction reagents may be those which shown for convenience, it can be appropriately modified within the scope of the definitions described above.
[0157]
[Organic synthesis reaction]
　The compounds of the present invention, an organic synthesis reaction, preferably a peptide synthesis and the like, in, such as a carboxyl group, i.e., can be used as a protective reagent in an amino acid or peptide. Specifically, a carboxyl group or a carboxamide group, C-terminal functional groups such as thiol groups, and the side chain functional group (hereinafter, referred to as C-terminal or the like.) Are preferably introduced protected as groups (anchor) of. When used as a protective reagent, or activated for the purpose of reacting with the substituents being protected, it may be reacted to convert the equivalent. Incidentally, the "organic compound protected by benzyl compounds of the present invention", referred to as "benzyl compound adduct".
[0158]
　Benzyl compounds of the present invention, various can be used as organic synthesis reactions protective reagent (anchor). For example, it can be carried out by the following steps.
Step (i) step of the present compound is dissolved in a soluble solvent (dissolution step),
step (ii) step of binding the present invention with the compound reaction substrate dissolved in a soluble solvent obtained in the above step (coupling step),
step (iii) step precipitating the resultant conjugate in the above step or a coupling product obtained in the above step was subjected to the reaction is dissolved in a soluble solvent, precipitating the product after the reaction (precipitation, step), and
step (iv) the conjugate obtained in step or the product after the reaction was re-dissolved in soluble solvent, removing the anchor from the conjugate or products after the reaction (deprotection step) .
[0159]
Step (i) (dissolution step)
　This step is a step of dissolving the present compound in a soluble solvent.
[0160]
　The solvent is a common organic solvent can be used for the reaction, the higher the solubility in the solvent, it is possible to expect excellent reactivity, it is preferable to select a high solubility of the present compound solvent. Specifically chloroform, halogenated hydrocarbons such as dichloromethane; 1,4-dioxane, nonpolar organic solvents such as tetrahydrofuran. These solvents may be used in a mixture at an appropriate ratio. Further, the above halogenated carbons and a non-polar organic solvents include benzene, toluene, xylene and the like aromatic hydrocarbons; acetonitrile, nitriles such as propionitrile; ketones such as acetone and 2-butanone; N, N - amides such as dimethylformamide; sulfoxides such as dimethyl sulfoxide, as long as the present invention compound is soluble, may be used in a mixture at an appropriate ratio.
[0161]
Step (ii) (binding step)
　This step is a step of bonding a reactive substrate with the present invention compound dissolved in a soluble solvent obtained in step (i).
[0162]
　And here reaction substrate, those having a -COOH group such as protected amino acid, the amount of the reaction substrate, the compound of the present invention 1 mole, can be 1 to 10 moles, preferably 1 to 5 it is the mole.
[0163]
　If Y is a hydroxyl group, in a solvent inert to the reaction, dimethylaminopyridine catalyst under ester bond by the addition of a condensing agent is formed.
[0164]
　When Y is a group NHR, 1-hydroxybenzotriazole (HOBt), 1-hydroxy-1H-1,2,3-triazole-5-carboxylic acid ethyl ester (hOCT), 1-hydroxy-7-azabenzotriazole ( HOAt) or the like of the condensation additive (condensation accelerator) the presence, with the addition of a condensing agent amide bond is formed.
[0165]
　The amount of the condensation additive, relative to the compound of the present invention 1 mole, preferably 0.05 to 1.5 mol.
[0166]
　As the condensing agent, dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC), N-ethyl--N'-3- dimethylaminopropyl carbodiimide and its hydrochloride (· EDC HCl), hexafluorophosphate (benzotriazol-1 yloxy) tripyrrolidinophosphonium (PyBop), O-(benzotriazol-1-yl) -N, N, N ', N'- tetramethyluronium tetrafluoroborate (TBTU), 1-[bis (dimethylamino) methylene] -5-chloro -1H- benzo triazolium 3-oxide hexafluorophosphate (HCTU), O-benzotriazol -N, N, N ', N'- tetramethyluronium tetrafluoroborate (HBTU) and the like and the like.
[0167]
　The amount of the condensing agent, for the present invention 1 mole of the compound can be 1 to 10 moles, preferably 1 to 5 mol.
[0168]
　As the solvent, for example, toluene, xylene and the like aromatic hydrocarbons; diethyl ether, tetrahydrofuran, and dioxane; chloroform, halogenated hydrocarbons such as or mixtures thereof such as dichloromethane. Among them, toluene tetrahydrofuran and the like are preferable.
[0169]
　The reaction temperature is usually -10 ° C. ~ 30 ° C., preferably from 0 ° C. ~ 20 ° C., the reaction time is usually 1 to 30 hours.
[0170]
　Check progress of the reaction can be applied the same method as the general liquid phase organic synthesis reactions. That is, it is possible to track the reaction using thin-layer silica gel chromatography, high performance liquid chromatography and the like.
[0171]
Step (iii) (precipitation step)
　In this step, bound product obtained in the above step (ii), or the coupling was dissolved in a soluble solvent, the product obtained after carrying out the desired organic synthesis reactions to isolate, the conjugate, or to change the solvent in which the product is dissolved (e.g., changes in solvent composition, change of the type of solvent) is a step of precipitation. That is, the reaction was carried out under conditions such conjugates is dissolved, after the reaction, the solvent was distilled off, binding was the precipitation culling impurities by solvent substitution. The displacement solvent, using a polar organic solvent such as methanol or acetonitrile. That the reaction was carried out under conditions such compound is dissolved, after the reaction, the solvent substitution, for example, the dissolved using halogenated solvents or THF or the like, to precipitate the polar organic solvent such as methanol or acetonitrile used.
[0172]
Step (iv) (deprotection step)
　This step is from the coupling was isolated by precipitation of the step (iii) or the product, finally removing the present invention compounds from the protected reagent (Anchor) is a step of obtaining the desired product.
[0173]
　Here the anchor to be removed, the formula (I-d):
[0174]
[Of 25]

[0175]
(Each group in the formula are the same as defined above)
is a group represented by.
[0176]
　If Y is a hydroxyl group, reacts with -COOH first reaction substrate, to form an ester bond, is deprotected, C-terminal, the peptide is -COOH. On the other hand, when Y is a group -NHR, -COOH group of reaction substrate becomes amide bond, if it is de-anchored, C-terminal, is converted into -CONHR group.
[0177]
　Y is only a if you want to selectively remove, the present invention compound group OR on the benzene ring as an anchor for the case of the hydroxyl groups a using anchor which is located the 2-position or 4-position, deprotection preferably performed by acid treatment to. The acid to be used, trifluoroacetic acid (hereinafter, TFA called.), Hydrochloric acid, sulfuric acid, methanesulfonic acid, p- toluenesulfonic acid and the like. Among them, TFA is preferably the concentration of these acids is 0.1 % to 5% of chloroform and dichloromethane, or may be carried out in solution under conditions of a THF solution.
[0178]
　Y is a hydroxyl group or an anchor is -NHR group, it is also possible to simultaneously remove the protective groups of other peptides. In that case, the art, especially conventional methods which are performed in the peptide synthesis is used, a method of adding an acid is preferably employed. TFA as the acid, hydrochloric acid, sulfuric acid, mesylate, tosylate, trifluoroethanol, hexafluoroisopropanol or the like is used. Among them TFA is particularly preferred.
　The amount of the acid is set depending on the kind of the acid used, amount adequate to remove the anchor is used. Relative to conjugate 1 mol, 3 can be ~ 100 moles, preferably 5 to 50 mol. With their use, as a further strong acid source, and trifluoromethanesulfonic acid, trimethylsilyl trifluoromethanesulfonate, BF 3 and the like can also be added,
[0179]
　The reaction temperature is usually 0 ° C. ~ 80 ° C., preferably from 0 ℃ ~ 30 ℃. The reaction time is usually 0.5 to 24 hours.
[0180]
　It can be produced peptides by utilizing the above steps. Benzyl compounds of the present invention can be mainly used as a protective reagent, such as C-terminal amino acid or peptide, but are not limited thereto. Also, benzyl compounds of the invention in which Y is a hydroxyl group, conventional methods in the art, for example, reaction of phosgene, it is possible to convert to the corresponding chloroformate member by, the chloroformate body it is also possible to use as a protective reagent such as N-terminal.
[0181]
　Method for producing a peptide using the above process specifically includes the following steps.
(1) A benzyl compound of the present invention, combined C-terminal or the like and condensation of N- protected amino or N- protected peptide, C- yield the protected amino or C- protected peptide step (C-terminal protective step),
(2) above removing temporary protective group of the N-terminal of the resulting amino acid or peptide in step (deprotection step of N-terminal),
(3) the N-terminus of the resulting amino acid or peptide in the above step, N- protected amino acid or step condensation of N- protected peptide (peptide chain elongation step), and
(4) precipitating the peptide obtained in the above step (precipitation step).
[0182]
Step (1) (C-terminal protection step)
　the process is a benzyl compound of the present invention, combined C-terminus and condensation of N- protected amino or N- protected peptide C- protected amino or C- protected peptide, i.e., benzyl compound adducts, to give compound. For example, it can be carried out according to the binding step described above.
[0183]
　The "N- protected amino" and "N- protected peptide" in the present invention, are protected amino group, a carboxyl group means an amino acid and peptide unprotected, is displayed as "P-AA-OH" obtained (P is an amino-protecting group (or, optionally also referred to a temporary protecting group.)).
[0184]
[Of 26]

[0185]
(Wherein, P is a protecting group of amino group, AA represents a group derived from an amino acid, Y 'represents O or NR. Other symbols are as defined above.)
　And benzyl compounds of the present invention N- condensation reaction at the C-terminus with protected amino acids or N- protected peptide is preferably carried out in a solvent inert to the reaction. For example, Y is a hydroxyl group, and in each case the radical -NHR, carried out in the presence of a condensing agent, Y is in the case of hydroxyl ester bond, Y is in the case of -NHR group to form an amide bond. As the condensing agent, for example, dicyclohexylcarbodiimide, diisopropylcarbodiimide, N- ethyl-N'-3- dimethylaminopropyl carbodiimide and its hydrochloride (EDC · HCl) and the like. When an ester bond formation reaction, in the presence of dimethylaminopyridine, upon amide bond formation reaction is carried out by a condensation additive presence of such HOBt and hOCT.
[0186]
　The solvent used in this step, chloroform, halogenated hydrocarbons such as dichloromethane; 1,4-dioxane, nonpolar organic solvents such as tetrahydrofuran. These solvents may be used in a mixture at an appropriate ratio. Preferably chloroform. The amount of the solvent used, to benzyl compounds of the present invention, preferably a 2 to 50 fold volume.
[0187]
　The reaction temperature is generally -10 ~ 40 ° C., preferably from 0 ~ 30 ° C.. The reaction time is usually 1 to 70 hours.
[0188]
Step (2) (deprotection step of N-terminal)
　The step is a step of removing temporary protective group for the N-terminus of the resulting amino acid or peptide in the above step (1).
[0189]
　As temporary protective group for the N-terminus, although the amino-protecting group commonly described later used in the art, such as peptide chemistry can be used, in the present invention, tert- butoxycarbonyl group (hereinafter, Boc group also referred to.), benzyloxycarbonyl group, and / or 9-fluorenylmethoxycarbonyl group (hereinafter, also referred to as Fmoc group.) is preferably used.
[0190]
　The deprotection conditions may be selected depending on the kind of the temporary protecting group, preferably a group which can be deprotected by conditions different from the removal of the protecting reagent from the compound of the present invention. For example, in the case of the Fmoc group is performed by treatment with a base, in the case of Boc group is effected by treatment with an acid. The reaction is carried out in a solvent which does not affect the reaction.
[0191]
　As the base, dimethylamine, diethylamine and the like. As the solvent, for example, chloroform, halogenated hydrocarbons such as dichloromethane; toluene, xylene and the like aromatic hydrocarbons; diethyl ether, tetrahydrofuran, dioxane and the like; nitriles such as acetonitrile and the like, or mixtures thereof and the like.
[0192]
Step (3) (peptide chain extension step)
　the process is the N-terminus of the N- terminal obtained in step (2) is de-protected amino acid or peptide, the condensation of N- protected amino or N- protected peptide it is a process.
[0193]
　The process is condensing agent according to the step (1), using a condensing additives is carried out in the peptide synthesis under conditions commonly used in the field of peptide chemistry.
[0194]
Step (4) (precipitation step)
　the process is carried out in the same manner as the precipitation step in the step (iii).
[0195]
　In the production method of the peptides of the present invention, the obtained N- protected amino or N- protected peptide in step (4), step (5) to (7) can be repeated as many times as desired.
(5) removing the temporary protecting group of the N-terminal of the peptide obtained in the precipitation step,
(6) obtained in the above step, the N-terminus of the peptide, condensation of N- protected amino or N- protected peptide step, and
(7) precipitating the peptide obtained in the above step.
[0196]
Step (5)
　the process is carried out in the same manner as the deprotection step of the N-terminal in the step (2).
[0197]
Step (6)
　the process is carried out in the same manner as the peptide chain extension step in the step (3).
[0198]
Step (7)
　the process is carried out in the same manner from a precipitate Kotei in step (iii).
[0199]
　In the production method of the peptides of the present invention, after the precipitation step of step (4) or step (7), C-terminal can further include a step of deprotecting the C-terminus of the peptide is protected with a benzyl compound. For example, the above is carried out analogously to anchor of the present invention in step (iv) deprotecting.
[0200]
　When the organic synthesis reaction or peptide synthesis reaction of the present invention comprises a multi-step, it can be omitted as appropriate the precipitation step in a range that does not affect the reaction in the subsequent step.

The scope of the claims

[Requested item 1]Formula (I):
[Chemical formula 1]

wherein,
Y represents a hydroxyl group or an -NHR group (. R is hydrogen atom, an alkyl group or an aralkyl group)
indicates; R a is an aliphatic hydrocarbon group represents an organic group having, is the total number of carbons in the organic group with 14 or more;
n number of R b are each independently an alkoxy group having 1 to 6 carbon atoms, halogen atoms or one or more halogens, be replaced by an atom also indicate an alkyl group having 1 to 6 carbon atoms; and
n represents an integer of 0-4. ]
Benzyl compound represented by.
[Requested item 2]
　R a total number of carbons in the organic group having an aliphatic hydrocarbon group is 14 to 200, according to claim 1 benzyl compounds described.
[Requested item 3]
　R a total number of carbons in the organic group having an aliphatic hydrocarbon group of 30-80, claim 1 benzyl compounds described.
[Requested item 4]
　n is 0 to an integer 2, and,
n pieces of R b are each independently an alkoxy group having 1 to 4 carbon atoms,
benzyl compound of any one of claims 1 to 3, .
[Requested item 5]
　R a has the formula (a):
[Formula 2]

wherein,
* represents a bonding
position; m 1 represents an integer of 1 ~
10; m 1 pieces of X 1 are each independently, or a single bond, or -O -, - S -, - COO -, - OCONH -, - NHCO- or -CONH-
indicates; R 1 and m 1 pieces of R 2 are each independently carbon the number 5 indicates a more divalent aliphatic hydrocarbon group; and
R 3 is a hydrogen atom or the formula, (I '):
[Chemical formula 3]

(wherein, * represents a binding position;
the other symbols , a group represented by the claims 1 represent the same meanings.). Groups represented by];
formula (b):
[Chemical formula 4]

(wherein,
*Indicates the binding
position; m 2 is 1 or 2 are
shown; n 1 , n 2 , n 3 and n 4 are each independently an integer of 0 ~
2; m 2 pieces of X 2 , m 2 pieces of X 2 ' and m 2 pieces of X 2 ' ' are each independently a single bond, or -O -, - S -, - COO -, - OCONH -, - NHCO- or It indicates
-CONH-; m 2 pieces of R 4 and m 2 pieces of R 6 are each independently a hydrogen atom, an aliphatic hydrocarbon group having at least 5 carbon methyl group or a carbon; and
R 5Indicates the number 5 or more aliphatic hydrocarbon group having a carbon. ) Groups represented by;
　formula (c):
[Chemical Formula 5]

(wherein,
* represents a bonding
position; m 3 represents an integer of 0 to
15; n 5 is an integer of 0 to 11
shown; n 6 represents an integer of 0 ~
5; m 3 pieces of X 3 are each independently a single bond, or -O -, - S -, - COO -, - OCONH-, and; it represents -NHCO- or -CONH-
m 3 amino R 7 groups are each independently hydrogen atom, represented by a methyl group or a 5 or more aliphatic hydrocarbon group having a carbon).; or
　formula (d):
[Chemical formula 6]

(wherein,
* represents a bonding
position; n 7 amino X 4They are each independently a single bond, or -O -, - S -, - COO -, - OCONH -, - NHCO- or -CONH-
indicates; R 8 is a divalent aliphatic hydrocarbon It represents a hydrogen
radical; n 7 amino R 9 are each independently a monovalent aliphatic hydrocarbon
group; n 7 is an integer of 1-5; and
Ar represents an arylene group. ) Or a group represented by
a, any one benzyl compound according to claim 1-4.
[Requested item 6]
　R a has the formula (a) [wherein, m 1 is an 1; X 1 is either a single bond or -O- and is; R 1 and R 2 are each independently carbon and R; a divalent aliphatic hydrocarbon group having 5 to 80 3 is a hydrogen atom or formula (I ''):
[Chemical formula 7]

(wherein, * represents a bonding position; Y . is as defined in claim 1) or formula (I '' '):
[formula 8]

(wherein, * represents a bonding position; Table in Y is as defined in claim 1). is a group. ; Group represented by]
the formula (b) (wherein, m 2 is an 1, n 1 , n 2 , n 3 and n 4 are each independently 0 or 1; X 2 , X 2 ' And X 2 ' ' are each independently a single bond, or -O- and is; R 4 and R 6 are each independently a hydrogen atom, a methyl group or a carbon number of 5-80 an aliphatic hydrocarbon group; and R 5 is an aliphatic hydrocarbon group having 5 to 80 carbon atoms. ) Groups represented by;
formula (c) (wherein, m 3 is an integer of 1 ~ 5; n 5 is an integer from 0 to
2; n 6 is an integer from 0 to 3 ; m 3 pieces of X 3 are both -O-; and, m 3 pieces of R 7 is represented by each independently an aliphatic hydrocarbon group having 5 to 80 carbon atoms). or; group that
the formula (d) (wherein, n 7 pieces of X 4 are both -O-; R 8 and n 7Number of R 9 are each independently a monovalent or divalent aliphatic hydrocarbon group having 5 to 80 carbon atoms; n 7 is an integer from 1 to 3; and Ar is is phenylene . ) The group represented by
is, claim 5 benzyl compounds described.
[Requested item 7]
　R a has the formula (a) (wherein, m 1 is an 1; X 1 is -O-; R 1 and R 2 are each independently an alkylene group having 8 to 60 carbon atoms in it; and R 3 .; is a hydrogen atom group represented by)
the formula (b) (wherein, m 2 is an 1, n 1 , n 2 , n 3 and n 4 are both is also a 1; X 2 , X 2 ' and X 2 ' ' are both -O-; and R 4 , R 5 and R 6 are each independently an alkyl group having 8 to 60 carbon atoms . in a) a group represented by;
formula (c) (wherein, m 3 is 2 or 3; n 5 is an 1; n 6 is 2 or 3; m 3 pieces of X 3 are both -O-; and, m 3 groups of R 7 are each independently an alkyl group having 8 to 60 carbon atoms. Or; group represented by)
the formula (d) (wherein, n 7 pieces of X 4 are both -O-; R 8 is an alkylene group having 1 to 3 carbon atoms; n 7 pieces of R 9 are each independently an alkyl group having 8 to 60 carbon atoms; n 7 is an integer from 1 to 3; and Ar is a group represented by phenylene).
a, 5. benzyl compounds described.
[Requested item 8]
　R a has the formula (a) (wherein, m 1 is an 1; X 1 is -O-; R 1 and R 2 are each independently an alkylene group having 14 to 30 carbon atoms in it; and R 3 .; is a hydrogen atom group represented by)
the formula (b) (wherein, m 2 is an 1, n 1 , n 2 , n 3 and n 4 are both is also a 1; X 2 , X 2 ' and X 2 ' ' are both -O-; and R 4 , R 5 and R 6 are independently each an alkyl group having 14 to 30 carbon atoms . in a) a group represented by;
formula (c) (wherein, m 3 is 2 or 3; n 5 is an 1; n 6 is an 3; m 3 pieces of X 3 are both -O-; and, m 3 pieces of R 7 is each, independently, an alkyl group having 14 to 30 carbon atoms. Or; group represented by)
the formula (d) (wherein, n 7 pieces of X 4 are both -O-; R 8 is an alkylene group having 1 to 3 carbon atoms; n 7 pieces of R 9 are each independently an alkyl group having 14 to 30 carbon atoms; n 7 is 2 or 3;. and Ar is a group represented by phenylene)
a claim 5-benzyl compounds described.
[Requested item 9]
　Group OR a is present in the 2-position or 4-position on the benzene ring, any one benzyl compound according to claim 1-8.
[Requested item 10]
　Group R b is a methoxy group, any one benzyl compound according to claim 1-9.
[Requested item 11]
　Y is a hydroxyl group, according to claim 1 to 10 any one benzyl compounds described description.
[Requested item 12]
　Y is (wherein, R is as defined claim 1.) -NHR group is, claims 1 to 10, benzyl compound according to any one of the described.
[Requested item 13]
　4- (12'-docosyloxy-1'-dodecyloxy) benzyl
alcohol; 4- (12' docosyloxy 1'dodecyloxy) -2-methoxybenzyl
alcohol; 4- (12' docosyloxy-1'-dodecyl oxy) -2-methoxy
benzylamine; 2- (12' docosyloxy 1'dodecyloxy) -4-methoxybenzyl
alcohol; 2- (12' docosyloxy 1'dodecyloxy) -4-methoxybenzylamine ;
4-methoxy-2- [3 ', 4', 5'-tris (octadecyloxy) benzyl] benzyl
alcohol; 2- [3 ', 5'-di (docosyloxy) benzyloxy] -4-methoxybenzyl alcohol ;
2-methoxy-4- [2 ', 2', 2'-tris (octadecyl oxymethyl) ethoxy] benzylidene Alcohol;
2-methoxy-4- [2 ', 2', 2'-tris (octadecyl oxymethyl) ethoxy]
benzylamine; 4-methoxy-2- [3 ', 4', 5'-tris (octadecyloxy ) cyclohexylmethyl] benzyl alcohol;
4- [3 ', 4', 5'-tris (octadecyloxy) cyclohexylmethyl] benzyl
alcohol; 1,22- bis [12- (4-hydroxymethyl-3-methoxyphenoxy ) dodecyloxy] docosane; and
1,22- bis [12- (2-hydroxymethyl-5-methoxyphenoxy) dodecyloxy] docosanoic
selected from the group consisting of benzyl compound according to any one of claims 11 or 12.
[Requested item 14]
　2-docosyloxy-4-methoxybenzyl
alcohol; 2-methoxy-4- [3 ', 4', 5'-tris (octadecyloxy) cyclohexylmethyl] benzyl
alcohol; 3,5-dimethoxy-4- [3 ', 4 ', 5'-tris (octadecyloxy) cyclohexylmethyl] benzyl
alcohol; N-(4-hydroxymethyl-3-methoxyphenyl) -3,4,5-tris (octadecyl) cyclohexyl
carboxamide; N-(5 - hydroxymethyl-2-methoxyphenyl) -3,4,5-tris (octadecyl) cyclohexyl carboxamide; and
N-(4-hydroxymethylphenyl) -3,4,5-tris (octadecyl) cyclohexyl carboxamide
consisting It is selected from the group, claims Benzyl compounds according to any one of 1 or 12.
[Requested item 15]
　Amino acid or peptide carboxyl protecting reagent consisting of benzyl compound of claim 11.
[Requested item 16]
　C-terminal protection reagent of an amino acid or a peptide consisting of benzyl compound of claim 11.
[Requested item 17]
　Comprising the following steps, the production method of peptides by liquid phase synthesis method;
(1) benzyl compound according to any one of claims 1 to 14, is attached to an amino acid or peptide step (coupling step), and
( 2) the obtained in the step, precipitating the coupling of an amino acid or peptide with benzyl compound (precipitation step).
[Requested item 18]
　Comprising the steps of a manufacturing method of the peptide by liquid phase synthesis method;
(1) C-terminal and condensation of the benzyl compound according to any one of claims 1 ~ 14, N- protected amino acid or N- protected peptide and, C- to obtain a protected amino acid or C- protected peptide (C-terminal protective step),
(2) removing the protecting group of the N-terminus of the resulting amino acid or peptide in the above step process (N-terminal deprotection step ),
(3) the N-terminus of the resulting amino acid or peptide in the above step, N- protected amino acid or N- protected peptide step condensation (peptide chain elongation step), and
(4) peptides obtained in the above step precipitating (precipitation step).
[Requested item 19]
　Further comprising repeating steps (5) to (7) one or more process according to claim 18, wherein the peptide;
removing the protecting group of the N-terminus of (5) peptides obtained in the precipitation step (N deprotection step ends),
(6) above the N-terminus of the peptide obtained in step, the step of condensing N- protected amino or N- protected peptide (peptide chain elongation step), and
obtained in (7) above step precipitating obtained peptide (precipitation step).
[Requested item 20]
　After the precipitation step, C-protected further comprising a C-terminal protecting group (anchor) removing the peptide production method of a peptide according to claim 18 or 19.
[Requested item 21]
　Method for producing a peptide compound using benzyl compound according to any one of claims 1 to 14.
[Requested item 22]
　Method for producing an organic compound using the benzyl compound according to any one of claims 1 to 14.
[Requested item 23]
　Characterized in that it is protected by a benzyl compound according to any one of claims 1 to 14, benzyl compound adducts.
[Requested item 24]
　Formula (III):
[Chemical Formula 9]

(wherein, m 3 'represents an integer of 1 ~ 3; m 3 ' number of R 7 'are each independently an alkylene group having 14 to 30 carbon atoms It is shown, and Z 'compound represented by a hydroxyl group or a leaving group.).
[Requested item 25]
　In formula (III), m 3 'is 3, and Z' is a hydroxyl group, a halogen atom, one or more optionally substituted by a halogen atom alkylsulfonyloxy group or an optionally substituted arylsulfonyl, oxy group, claim 24 a compound according.