We claim:
1. A substantially pure D-penicillamine (I) having purity greater than 99.0% by HPLC.
2. The D-Penicillamine (I) according to claim 1 is having purity greater than 99.0%
by HPLC and wherein one or more of the following: i. less than 0.15% of L-penicillamine ii. less than 0.15% of Trisulfide impurity iii. less than 0.5% of Disulfide impurity iv. mercuric content less than 1 Oppm
3. A process for the preparation of D-penicillamine (I) with purity greater than
99.0% purity comprising:
a) reacting 2-isopropyl-5,5-dimethylthiazolidine-4-carboxylic acid hydrochloride (IV) with hydroxylamine hydrochloride in presence of base to form 2-amino-3-methyl-3-sulfanylbutanoic acid (III);
b) resolution of 2-amino-3-methyl-3-sulfanylbutanoic acid (III) using suitable acid to form (2S,3S)-2,3-dihydroxysuccinic acid :(S)-2-amino-3-mercapto-3-methylbutanoic acid (1:1) (II);
c) purification of (2S,3S)-2,3-dihydroxysuccinic acid : (S)-2-amino-3-mercapto-3-methylbutanoic acid (1:1) (II) by passing through a micron filter to form pure (2S,3S)-2,3-dihydroxysuccinic acid :(S)-2-amino-3-mercapto-3-methylbutanoic acid (1:1) and
d) treating (2S,3S)-2,3-dihydroxysuccinic acid:(S)-2-amino-3-mercapto-3-methylbutanoic acid (1:1) in presence of an organic base to form (2S)-2-amino-3-methyl-3-sulfanylbutanoic acid (I).
4. The process according to claim 3, wherein the protic solvent used in step a) is
selected from the group consisting of water, methanol, ethanol, isopropanol, n-propanol, n-butanol or mixture thereof.
5. The process according to claim 3, wherein aprotic solvent used in step a) is
selected from dichloromethane, chloroform, dichloroethane, acetonitrile, dimethyl sulfoxide, tetrahydrofuran, dimethylformamide, ethyl acetate or mixture thereof.
6. The process according to claim 3, wherein the base used in step a) is selected
from the group consisting of potassium hydroxide and sodium hydroxide.
7. The process according to claim 3, wherein step a) the optimum pH range is
maintained in the range of 4.5-5.5.
8. The process according to claim 3, wherein the acid used in step b) is D-tartaric
acid.
9. The process according to claim 3, wherein the organic base used in step d) is
selected from the group consisting of triethyl amine, pyridine, 4-dimethylaminopyridine and di isopropyl ethyl amine.
10. A process for the preparation of (2S,3S)-2,3-dihydroxysuccinic acid :(S)-2-amino-3-mercapto-3-methylbutanoic acid (1:1) (II) by treating 2-amino-3-methyl-3-sulfanylbutanoic acid (III) with D-tartaric acid under suitable temperature conditions.