FLUORINATED CATHARANTHINE DERIVATIVES, THEIR PREPARATION AND THEIR UTILISATION AS VINCA DIMERIC ALKALOID PRECURSORS The present invention relates to fluorinated derivatives of catharanthine, their preparation and their use as a precursor of fluorinated dimeric Vinca alkaloids, and vinflunine in particular. Vinflunine 1 is a wide-spectrum anticancer agent developed by Pierre Fabre laboratories. This molecule is a fluorinated analogue of vinorelbine 5 (Navelbine®) which is the reference drug for treatment of breast and lung cancer. The structure of vinflunine is very similar to that of vinorelbine, from which it differs only by the presence of a group gem-difluorinated in C20', and by the absence of the double bond C3-C4, . Vinflunine 1 (Javlor®) is the most active fluorinated compound discovered over recent years. It is currently in phase III of clinical trials in the treatment of breast, bladder and lung cancer, and is heralded today as the most promising molecule to have originated from the family of Vinca alkaloids. Vinflunine may be prepared from 3',4'-anhydrovinblastine 4 precursor which is obtained by the coupling of two sub-units catharanthine 2 and vindoline 3, which are extracted directly from the leaves of the Madagascar periwinkle (Diagram 1) . Alternatively vinflunine may be prepared by direct fluorination of vinorelbine. (Diagram Removed) Diagram 1 3' , 4' -Anhydrovinblastine 4 can then be transformed into vinorelbine 5 by ring contraction, or into vinflunine 1 by introduction of two fluorine atoms on the lateral chain of the "north" fragment followed by ring contraction (Diagram 2) . This fluorination operation takes place in a superacid medium (HF-SbF5) in the presence of a chlorinated solvent. These reaction conditions are particularly drastic, resulting in partial degradation of the dimeric alkaloid 4 and thus in a drop in the overall chemical yield of the transformation. The gem-difluorination in C20 proceeds with concomitant reduction of the C3.-C4 double bond. The stereocentre formed at 4', has an absolute configuration (R) . Vinflunine can also be prepared by fluorination of vinorelbine 5 (Navelbine®) . The synthesis thereof is carried out by ring contraction of 3',4'-anhydrovinblastine 4. (Diagram Removed) Diagram 2 3' , 4'-Anhydrovinblastine 4 is a product with high added. The fluorination stage thus causes the sacrifice of a considerable quantity of this precious intermediate. This situation risks resulting at times in a strong increase in the demand for periwinkle leaves. Several strategies are being studied for continuing the development of vinflunine 1. Based on the observation that the fluorination of 3', 4'-anhydrovinblastine in a superacid mixture modifies only its "north" fragment which originates from catharanthine, a solution consisting of introducing fluorine atoms directly to the skeleton of catharanthine 2 has been advocated, within the scope of the present invention. This approach has a number of advantages: it introduces fluorine upstream in the synthesis to a product with lesser added value than 3',4'-anhydrovinblastine 4. The synthesis of vinflunine could then be accessed via a biomimetic coupling with vindoline 3. In fact, 20',20'-difluorocatharanthine 6 can then be coupled to vindoline 3 to obtain 3', 4'-anhydro-20',20'-difluorovinblastine 7. The latter is finally converted into vinflunine 1, in a process familiar to the specialist, by ring contraction reaction followed by reduction of the non-saturated C3'-C4 double bond. (Diagram 3) . (Diagram Removed) This approach also allows access to other original difluorinated derivatives (3',4'-anhydro-20',20'-difluorovinblastine 7, 20',20'-difluorovinorelbine 8) which are not accessible under conventional superacid conditions. These molecules are all the more interesting since study of the structure activity relation has shown that the region 4' and 20' of the Vinca alkaloids is strongly associated with their anti-tumoral activity. Also, the coupling of synthesis intermediates (and derivatives) of fluorinated catharanthine likewise produces other original fluorinated derivatives of dimeric alkaloids of Vinca. Therefore, the present invention relates to fluorinated derivatives of catharanthine responding to the general formula I: (Formula Removed) in which: the dotted line expresses the possibility of the presence of a double bond when the substitution -X is absent or else of a single bond when -X designates a substitution for a group: H, • OR, NR'R", • SR, or an atom of halogen with R, R' and R" designating independently of one another an atom of hydrogen or a linear or branched alkyl group in C1 to C6, R1, R2 and R3 represent independently of one another an atom of hydrogen, fluorine or a methylated group, on the condition all the same that at least one of the radicals R1 and R2 represents an atom of fluorine, and - n = 1 or 2. The present invention likewise relates to the utilisation of these fluorinated derivatives as synthesis intermediates useful for the preparation of fluorinated dimeric alkaloids of Vinca, in particular as reactive partners in coupling reactions with vindoline or with a derivative of vindoline. In particular, vinflunine will be obtained by coupling vindoline and 20,20-20,20-difluorocatharanthine, resulting in 20',20'-difluoro-3',4'-anhydrovinblastine which, in turn, will be subjected to a ring contraction reaction followed by a reduction reaction of the endocyclic double bond at position Introduction of the fluorine atoms to catharanthine 2 could be envisaged via oxidation of the lateral chain of catharanthine and fluorination. (Diagram Removed) Diagram 4 The preparation of the fluorinated catharanthine derivatives of the invention implies thus an oxidation step of the lateral chain of catharanthine, which is carried out in conditions leading to an oxidised derivative of catharanthine responding to the general formula II: (Formula Removed) in which: n = 1 or 2, X designates a C=0 or C=S group, Y designates a CO2R, SO2R or COR group with R designating an aryl group or a linear or branched alkyl group in C1 to C4, and Z designates a CH-OH or C=0 group. Therefore, the present invention relates also to oxidised derivatives of catharanthine responding to the general formula II: (Formula Removed) in which: n - 1 or 2, X designates a C=0 or C-S group, Y designates a CO2R, SO2R or COR group with R designating an aryl group or a linear or branched alkyl group in C1 to c4, and Z designates a CH-OH or C=0 group. A preferred oxidised derivative of catharanthine according to the formula II is a derivative wherein: - n = 2, X designates a C=0 group, Y designates a CO2R group with R designating a linear or branched alkyl group in C1 to C4, and Z designates a CH-OH or C=0 group. The present invention likewise relates to the use of these oxidised derivatives as synthesis intermediates useful for the preparation of fluorinated dimeric alkaloids of Vinca, in particular vinflunine. This preparation implies a fluorination of the oxidised derivative of catharanthine followed by deprotection of the two nitrogen atoms, resulting in a fluorinated derivative of catharanthine of the invention. The preparation further implies a coupling reaction between the said fluorinated derivative and vindoline or a derivative of vindoline. In particular, vinflunine will be obtained by coupling vindoline and 20,20-difluoro-catharanthine, obtained by fluorination and deprotection of the two nitrogen atoms of an oxidised derivative of catharanthine as defined above for which n = 2, X = C=0, Y = CO2R with R as defined above and Z = C=0, resulting in 20',20'-difluoro-3',4'-anhydrovinblastine which, in turn, will be subjected to a ring contraction reaction followed by a reduction reaction of the endocyclic double bond at position C3'-C4'. The term "aryl" refers herein to a cyclic aromatic group of from 5 to 7 carbon atoms, comprising optionally a heteroatom, in particular an oxygen or a nitrogen, such as, for example, a phenyl or a pyridinyl group. Thus, as an example, 20,20-difluorocatharanthine can be synthesised as follows. Activation of the lateral chain can be achieved by isomerisation of the endocyclic double bond to the endocyclic position prior to further functionalisation. The isomerisation reaction of 2 in 10 is performed under partial hydrogen pressure in the presence of palladium on carbon. The indole ring is then protected in the form of methyl carbamate 11 and tertiary nitrogen in the form of amide 12. (Diagram Removed) Diagram 5 The double bond of 12 is then dihydroxylated by Os04 and the resulting diol 13 is activated twice in the form of cyclic sulphate 14. The allylic alcohol 15 is obtained by action of tetrabutyl ammonium fluoride, followed by treatment with sulphuric acid. The alcohol function is then oxidised by Mn02 and the resulting enone 16 is difluorinated by action of Deoxofluor™ (bis(2-methoxyethyl)aminosulfide trifluoride). The protective group of indole (carbamate) is eliminated by the action of potassium carbonate in methanol. The amide group of 17 is finally reduced to result in 20,20- difluorocatharanthine 6. The latter can, in the same way as catharanthine of natural origin, be coupled to vindoline to provide the fluorinated analogue of 3',4'-anhydrovinblastine (7) which, after ring contraction, results in the fluorinated analogue of vinorelbine (8) . Finally, selective reduction of the double bond of the north fragment results in the formation of vinflunine 1. According to a variant synthesis route, the allylic alcohol 15 can also be obtained by an initial protection of the indole ring of catharanthine 2 by a methyl carbamate (compound 26) and of tertiary nitrogen in the form of amide 27. The latter can then be oxidised directly in allylic alcohol 15 by Se02 (Diagram 6) . (Diagram Removed) Diagram 6 The synthesis intermediates to 20,20-difluorocatharanthine 6 can be exploited by functional arrangements which do not result in 20,20-difluorocatharanthine but in structural analogues. These analogues can, in the same way as catharanthine of natural origin, be coupled to vindoline to result in the corresponding fluorinated dimeric alkaloids. Accordingly, starting from the intermediate 13 oxidation of the secondary alcohol function gives access to ketone 18. Fluorination of the ketoalcohol 18 by DAST (diethylaminosulphide trifluoride) generates difluoro-alcohol 19. The latter could, after the usual stages of deprotection (— 20) be coupled to vindoline to form the difluorinated analogue 21 of vinblastine which is likewise an alkaloid having notable anticancer properties (Diagram 7) . (Diagram Removed) Diagram 7 Moreover, the introduction of a single fluorine atom to the catharanthine skeleton is possible from the intermediate 15 (Diagram 8). When the latter is treated by DAST, the monofluorinated product of the lateral chain (22) is formed. As already mentioned hereinabove, this product results in the mono fluoro analogues 3',4'-anhydro-20' -fluorovinblastine 24 and 20'-f luorovinorelbine 25 which can lead to the monofluorinated analogue of vinflunine by an additional stage of reduction of the double bond. (Diagram Removed) Diagram 8 Finally, isocatharanthine 10 can also be used as a synthesis intermediate in the preparation of fluorinated dimeric alkaloids of Vinca, and in particular vinflunine. This preparation implies a coupling reaction between the said isocathranthine and vindoline or a derivative of vindoline. Thus, vinflunine 1 can be obtained by coupling vindoline 3 and isocatharanthine, resulting in 4',20'-anhydrovinblastine 28. This intermediate can then be difluorinated using the conditions described for the fluorination of 3',4'-anhydrovinblastine 4 (J.-C. Jacquesy et al., Journal of Fluorine Chemistry, 2002, 114, 139). The obtained product, (4'R)-4'-deoxy-20',20'-difluorovinblastine 30, is identical to the product formed by fluorination of 3',4'-anhydrovinblastine 4. Transformation of 30 in vinflunine 1 by ring contraction is described in literature (J.-C. Jacquesy et al.. Journal of Fluorine Chemistry, 2002, 114, 139) (Diagram 9). Alternately, vinflunine 1 can be also obtained by ring contraction of 4',20'- anhydrovinblastine 28, resulting in 29, followed by a gem difluorination according to the same methods as described above. (Diagram Removed) Diagram 9 It appears that the present invention offers an alternative strategy to the classic synthesis of vinflunine, allowing the use of a more efficacious and thus more economic process. In addition, the utilisation of fluorinated intermediates of catharanthine according to the invention, for example: 20-fluorocatharanthine 23 and 20,20-difluoro-3-hydro-4-hydroxycatharanthine 20, in coupling reactions with vindoline 3, permits preparation of novel dimeric alkaloids having potential anti-cancer activities. Other specific structural analogues of vinorelbine and vinflunine are easily accessed by this method. All the preparation methods and reaction diagrams described hereinabove have been detailed in the case of preparation of fluorinated derivatives of catharanthine responding to the general formula (I) in which n = 2. All the corresponding derivatives responding to the general formula (I) in which n = 1 can be easily obtained by a process of ring contraction of the northern, catharanthine derived, portion of the dimers, by techniques familiar to the specialist and in particular those described by Andriamialisoa, R.2. ; Langlois, N. ; Langlois Y. ; Potier P. Tetrahedron, 1980, 36, 3053-30 60. The present invention will now be described in greater detail by means of the preparation examples mentioned hereinbelow by way of illustration of the principal stages resulting in the fluorinated derivatives of catharanthine, and in particular in 20,20-difluorocatharanthine. Isocatharanthine (10) (Formula Removed) To a suspension of palladium (10% in mass) on carbon (5.1 q, 5.4 mmol, 0.2 equiv.) previously activated by hydrogen in MeOH (150 mL) is added ( + }-catharanthine 2 (9.0 g, 26.8 mmol, 1 equiv.) in solution in MeOH (100 mL) . The reaction mixture is placed under reduced pressure in hydrogen (0.3 bar) , then isolated and left under reduced stirring at ambient temperature. The reaction is followed by XH NMR until the starting product disappears (around 2 h). The reaction mixture is then filtered on celite 545, then recrystallised in MeOH to give the compound 10 (6.5 g, 19.3 mmol, 72%) in the form of translucent crystals. Chemical formula: (Formula Removed) Rf = 0.35 (Hexane/ AcOEt 3/7) F = 78°C-81°C *H NMR (CDC13) : 8.08 (si, 1H, NH) ; 7.53 (d, J = 7.3 Hz, 1H, H-ll) ; 7.26 (d, J = 7.3 Hz, 1H, H-14) ; 7.22-7.10 (m, 2H, H-12 and H-13) ; 5.48-5.32 (m, 1H, H-20) ; 4.05 (s, 1H, H-5) ; 3.73 (s, 3H, CO2CH3) ; 3.62-3.46 (m, 1H, H-7) ; 3.44-3.24 (m, 2H, H-7 and H-8) ; 3.18-3.10 (m, 1H, H-19) ; 3.08-2.92 (m, 2H, H-19 and H-8) ; 2.88-2.74 (m, 1H, H-l) ; 2.44-2.26 (m, 2H, H- 3); 2.20-2.08 (m, 1H, H-2) ; 1.90-1.78 (m, 1H, H-l) ; 1.62 (d, J = 6.7 Hz, 3H, H-21). 13C NMR (CDC13) : 175.2 ; 137.7 ,- 135.9 ; 129.5 ; 122.6 ; 120.1; 119.4 ; 119.0 ; 111.2 ; 111.1 ; 64.2 ; 56.1 ; 53.8 ; 53.3 ; 51.1 ; 38.0 ; 30.3 ; 27.9 ; 22.0 ; 13.4. IR {film): 3368, 2916, 2855, 1714, 1461, 1264, 740 cm-1. MS (ESI TOF) : 337 [M+H+] (100) . [α]D20 - + 35 (c = 2.3 ; CHCl3) Na-carbomethoxyisocatharanthine (11) (Formula Removed) To a suspension of potassium hydride (0.72 g, 6.3 mmol, 1.5 equiv.) in THF (10 mL) at 0°C is added dropwise a solution of 10 (1.35 g, 4 mmol, 1 equiv.) in THF (20 mL) . After 30 minutes under stirring at 0°C, methyl chloroformate (0.5 mL, 6.3 mmol, 1.5 equiv.) is added dropwise. After 1 h under stirring at 0°C, the reaction medium is brought to ambient temperature and agitation is maintained for 18 h. An aqueous solution of saturated K2CO3 (10 mL) is added. The aqueous phase is extracted with CH2C12 (3x20 mL), the organic phases are collected, dried on Na2SO4 and concentrated under vacuum. The crude product is then purified by chromatography on silica (Eluent: CH2Cl2/MeOH 97/3) to give 11 (1.3 g, 3.3 mmol, 82%) in the form of a white solid. Chemical formula (Formula Removed) Rf = 0.4 (CH2Cl2/MeOH 94/6) F - 620C-640C lH NMR (CDC13) : 8.08 (d, J= 7.9 Hz, 1H, H-ll) ; 7.48 (d, J = 7.3 Hz, 1H, H-14) ; 7.38-7.16 (m, 2H, H-12 and H-13) ; 5.32-5.18 (m, 1H, H-20) ; 4.06 (s, 1H, H-5) ; 3.86 (s, 3H, CO2CH3) ; 3.68 (m, 1H, H-7) ; 3.54 (s, 3H, CO2CH3) ; 3.40-3.12 (m, 2H, H-7 and H-8) ; 2.99 (m, 1H, H-19) ; 2.86 (m, 1H, H-19) ; 2.80- 2.65 (m, 2H, H-8 and H-l) ; 2.44 (d, J = 16 Hz, 1H, H-3) ; 2.30 (d, J = 16 Hz, 1H, H-3) ; 2.06 (m, 1H, H-2) ; 1.76 (d, J = 14Hz, 1H, H-l) ; 1.56 = + 97 (c - 0.5 ; CHC13) (4K, 20K)-Na-carbomethoxy-3-hydro-4,20-dihydroxysulphate-19-oxocatharanthine (14) (Formula Removed) To a solution of diol 13 (200 mg, 0.45 mmol, 1 equiv.) in CH2C12 (5 mL) at 0°C are added triethylamine (0.15 mL, 1.04 mmol, 2.3 equiv.) then, dropwise, thionyl chloride (43 uL, 0.59 mmol, 1.3 equiv.). After 30 min at 0°C, the reaction is stopped by adding a solution saturated in NaCl (5 mL) and water (5 mL) . The aqueous phase is extracted with CH2C12 (3x10 mL) . The organic phases are combined, dried on Na2SO4 and concentrated under vacuum. The crude product is then placed directly into a mixture of 7.5 mL CH3CN and 6.5 mL H20 and is stirred vigorously. RuCl3 (5 mg, 0.023 mmol, 0.05 equiv.) and NaIO4 {242 mg, 1.13 mmol, 2.5 equiv.) are then added successively and after lh30 Et20 (12 mL) is added. Agitation is prolonged for 10 min. The aqueous phase is extracted by 3x10 mL Et20 then the combined organic phases are washed with water (30 mL), a solution saturated in NaHCO3 (30 mL) and a solution saturated in NaCl (30 mL) . The organic phase is then dried on Na3SO4 and concentrated under vacuum. Purification by chromatography on silica (eluent CH2Cl2/MeOH 98/2) results in 14 (137 mg, 0.27 mmol, 60%) in the form of a white solid. Chemical formula: (Formula Removed) Rf - 0.5 (CH2Cl2/MeOH 95/5) F = 140°C-142°C 1H NMR (CDCl3) : 7.98 (d, J = 7.3 Hz, 1H, H-ll) ; 7.44 (d, J = 7.3 Hz, 1H, H-14) ; 7.37-7.30 (m, 2H, H-12 and H-13) ; 5.12 (s, 1H, H-5) ; 4.75 (q, J = 6.7 Hz, 1H, H-20) ; 4.24-4.13 (m, 1H, H-5) ; 3.99 (s, 3H, CO2CH3) ; 3.68 (s, 3H, CO2CH3) ; 3.53-3.47 (m, 1H, H-7) ; 3.35-2.95 (m, 2H, H-8) ; 2.97 (dd, J = 14.0 Hz and J = 1.6 Hz, 1H, H-l) ; 2.90-2.85 (m, 1H, H-2) ; 2.45-2.38 (m, 2H, H-3) ; 2.02-1,96 (m, 1H, H-l) r- 1.64 (d, J = 6.7 Hz, 3H, H-21). 13C NMR (CDC13) : 173.2 ; 171.5 ; 152.4 ; 136.1 ; 134.8 ; 129.3; 125.6 ; 123.5 ; 118.8 ; 117.5 ; 116.0 ; 94.8 ; 84.9 ; 56.9 ; 55.1 ; 54.0 ; 53.4 ; 40.9 ; 38.4 ; 37.7 ; 32.3 ; 21.2 ; 15.8. IR (tablet KBr) : 1735, 1687, 1459, 1382, 1215, 904 cm"1. MS (ESI TOF) : 505 [M+H+] (100); 1009 fM+Na'j (13). [a]D20 = + 165 (c = 0.3 ; CHCl3) (20R) -Na-carbomethoxy-20-hydroxy-19-oxocatharanthine (15) To a solution of sulphate 14 (1.59 g, 3.16 mmol, 1 eguiv.) in THF (25 mL) is added dropwise a solution of NBu4F (1M in THF, 6.3 mL, 6.3 mmol, 2 equiv.). After 18h of stirring at ambient temperature, a solution of H2SO4 2M in THF (37 mL) and 3.7 mL water are added. After 48h of stirring at ambient temperature, a solution saturated in NaHCO3 is added (200 mL). The aqueous phase is extracted with AcOEt (4x50 mL) , the organic phases are combined, dried on Na3SO4, filtered then concentrated under vacuum. The crude product is then purified by chromatography on silica and 15 (828 mg, 1.95 mmol, 62%) is isolated in the form of a white solid. Chemical formula: (Formula Removed) Rf = 0.3 (CH2Cl2/MeOH 95/5) F = 188°C-190°C 1H NMR (CDC13) : 7.98 (d, J= 7.9 Hz, 1H, H-ll) ; 7.44 (d, J = 7.9 Hz, 1H, H-14) ; 7.35-7.20 (m, 2H, H-12 and H-13) ; 6.43 (d, J = 6.3 Hz, 1H, H-3) ; 5.24 (d, J = 1.7Hz, 1H, H-5) ; 4.41-4.33 (m, 1H, H-20) ; 4.17-4.03 (m, 1H, H-7) ; 3.94 (s, 3H, CO2CH3) ; 3.57 (s, 3H, CO2CH3) ; 3.47-3.17 (m, 4H, H-8, H-2 and H-7) ; 2.88 (dd, J = 14.0 Hz and J = 1.8 Hz, 1H, H-l) ; 2.02 (dd, J = 14.0 Hz and J = 1.8 Hz, 1H, H~l) ; 1.33 (d, J = 6.1 Hz, 3H, H-21). 13C NMR (CDCI3) : 174.1 ; 173.8 ; 152.0 ; 145.3 ; 136.6 ; 135.3; 129.3 ; 128.5 ; 125.1 ; 123.1 ; 118.4 ; 116.7 ; 115.8 ; 67.1 ; 58.0 ; 54.3 ; 53.6 ; 52.8 ; 44.0 ; 40.7 ; 38.4 ; 21.3 ; 21.1. IR (tablet KBr) : 3414, 2944, 1743, 1653, 1458, 1437, 1327, 1242, 754 cm-1. MS (ESI TOF): 447 [M+NaT] (100); 871 [2M+Na+] (64). [α]D20 - +181 (c = 0.7 ; CHC13) (Formula Removed) Na-carbomethoxy-19,20-dioxocatharanthine (16) A solution of allylic alcohol 15 (100 mg, 0.236 mmol, 1 equiv.) in 8 ml of dichloromethane is cooled to 0°C. 140 mg of activated manganese dioxide (16 mmol, 70 equiv.) are added to this at once. The black suspension obtained is stirred at 0°C for lh30 under nitrogen atmosphere then brought to ambient temperature. The reaction mixture is filtered on celite 54 5 then washed thoroughly using dichloromethane. The filtrate is concentrated under reduced pressure to give the enone 16 (85 mg, 0.201 mmol, 85%) in the form of a white solid. Chemical formula: (Formula Removed) R'f = 0.4 {EtOAcJ F = 108°C-110°C 1R NMR (CDC13) : 8.01 (d, J= 8.5 Hz, 1H, H-ll) ; 7.49 (d, J = 7.3 Hz, 1H, H-14) ; 7.45 (d, J = 6.7 Hz, 1H, H-3) ; 7.37-7.23 (m, 2H, H-12 and H-13) ; 5.80 (d, J = 1.8 Hz, 1H, H-5) ; 4.18- 4.02 (m, 1H, H-7) ; 3.91 (s, 3H, CO2CHs) ; 3.65 (m, 1H, H-2) ; 3.49 (s, 3H, CO2CH3) ; 3.48-3.34 (m, 1H, H-8) ; 3.32-3.16 (m, 2H, H-7 and H-8) ; 2.82 (dd, J = 12.8 Hz and J - 2.4 Hz, 1H, H-l) ; 2.35 (s, 3H, H-21) ; 2.07 (dd, J= 13.4 Hz and J= 3.0 Hz, 1H, H-l). 13C NMR (CDCl3) : 193.3 ; 172.2 ; 171.6 ; 151.9 ; 143.6 ; 142.3; 135.8 ; 135.3 ; 129.2 ; 125.2 ; 123.1 ; 118.4 ; 117.0 ; 115.8 ; 57.3 ; 53.5 ; 52.6 ; 52.5 ; 45.5 ; 41.3 ; 37.4 ; 24.6; 20.9. IR (tablet KBr) ; 1740, 1668, 1252, 751 cm"1. MS (ESI TOF) : 423 [M+H+] (10); 445 [M+Na+] (100); 867 [2M+Na+] (32) . HEMS (TOF MS ES+): Value calculated for C23H22N20GNa 445.1376 Value found 445.1357 [α]D20 = + 183 (c = 1.8 ; CHC13) 20, 20-difluoro-19-oxocatharanthine (17) Fluozination: NA-carbomethoxy-20, 20-difluoro-19- oxocatharanthine (Formula Removed) The enone 16 (300 mg, 0.71 mmol, 1 equiv.) is placed in solution in Deoxofluor™ (3 mL, 16.4 mmol, 23 equiv.). Three drops of ethanol are then added and the reaction mixture is left under stirring at 80°C for 24 h. 0.6 mL of Decxofluor™ (3.3 mmol, 5 equiv.) and two drops of ethanol are then added and agitation is continued at this temperature for a further 48 h (the reaction is' followed by 1H NMR until the starting product disappears). The reaction medium is diluted in 200 mL of dichloromethane and 100 mL of an aqueous solution saturated in K2CO3 are then added. The mixture is left for 15 min under stirring at ambient temperature, then the aqueous phase is extracted by 3×50 mL of dichloromethane. The organic phases are combined., dried on Na2SO4 and concentrated under vacuum. The crude product is then purified by two filtrations on silica gel (CH2Cl2/MeOH 98/2 and C6H12/AcOEt 6/4) and the residue enters the following stage. Chemical formula: (Formula Removed) Rf = 0.3 (Hexane/AcOEt 40/60) 'H NMR (CDCI3) : 8.01-7.99 (m, 1H, H-ll) ; 7.53-7.47 (m, 1H, H-14} ; 7.38-7.28 (m, 2H, H-12 and H-13) ; 6.87-6.77 (m, 1H, H-3) ; 5.36 (d, J = 1.8 Hz, 1H, H-5) ; 4.20-4.03 (m, 1H, H-7) ; 3.93 (s, 3H, CO2CH3) ; 3.61-3.54 (m, 1H, H-2) ; 3.57 (s, 3H, CO2CH3) ; 3.45-3.20 (m, 3H, H-8 and H-7) ; 2.93-2.83 (m, 1H, H-l) ; 2.09-1.98 (m, 1H, H-l) ; 1.81 (dd, J = 18 Hz, J = 18 Hz, 3H, H-21). Deprotection of indole: 20,20-difluoro-19- oxocatharanthine (17) (Formula Removed) To a solution of the above protected 20,20-difluorocatharanthine in 100 mL of methanol are added in one time 2 g of potassium carbonate (14.5 mmol) and the suspension is stirred at ambient temperature for 18 h. 50 mL of water are then added to the now limpid reaction medium and the mixture is extracted by 3x50 mL dichloromethane. The combined organic phases are dried on Na2SO4 and concentrated under reduced pressure. The residue obtained is precipitated in a cyclohexane/ ethyl acetate mixture 7/3 to give 17 {118 mg, 0.307 mmol, 43% in two steps) in the form of a white solid. Chemical formula: C2IH2oF2N2Oj M = 386 g.mol I Rf = 0.3 (CH2Cl2/MeOH 95/5) 1H NMR (CDC13) : 7.95 (s, 1H, NH) ; 7.52 (d, J = Hz, 1H, Jill) ; 7.26 (d, J = Hz, 1H, H-14) ; 7.16-7.11 (m, 2H, H-12 and H-l3) ; 6.83 (m, 1H, H-3) ; 5.55 (d, J = 1 Hz, 1H, H-5) ; 4.24 (m, 1H, H-7) ; 3.67 (s, 3H, CO2CH3) ; 3.58 (m, 1H, H-2) ; 3.36-3.24 (m, 3H, H-8 and H-7) ; 2.82 (dd, J = 13 HE, J = 2 Hz, 1H, H-l) ; 2.27 (dd, J = 13 Hz, J = 2 Hz, 1H, H-l) ; 1.82 (dd, J = 18 Hz, J = 18 Hz, 3H, H-21). 13C NMR (CDCI3) : 172.8 ; 171.6 ; 139.5 (t, J = 30 Hz) ; 135.8 ; 135.2 (t, J = 9 Hz) ; 133.8 ; 127.7 ; 122.4 ; 119.7 ; 119.1 (t, J = 233 Hz) ; 118.4 ; 110.6 ; 108.8 ; 56.3 ; 53.6 ; 53.0 ; 44.0 ; 42.8 ; 35.6 ; 22.4 (t, J = 28 Hz) ; 20.7. [α]D20 = + 155 (c = 0.4 ; CHC13) . 20,20-difluorocatharanthine (6) (Formula Removed) To a solution of 17 (140 mg, 0.36 mmol, 1 equiv.) in 50 mL of tetrahydrofurane are added in one time 360 mg of sodium borohydride (9.5 mmol, 26.5 equiv.). The resulting suspension is cooled to 0°C and placed under stirring and nitrogen atmosphere. 1.9 mL (14.6 mmol, 40.5 equiv.) of trifuoroborane diethylic etherate are added dropwise, then the reaction mixture is brought to ambient temperature and stirred for 3h. The solvent is evaporated under vacuum and replaced by 30 mL of methanol to which are added 6 mL of water and 4.5 mL of a solution of hydrochloric acid at 10%. The whole is stirred at ambient temperature for 15h. The methanol is evaporated and replaced by 20 mL of dichloromethane. The medium is neutralised by addition of 40 mL of an aqueous solution saturated in sodium hydrogenocarbonate then extracted by 3*20 mL of dichloromethane. The combined organic phases, dried on Na2SO4, are concentrated under reduced pressure. Purification of the residue by chromatography on silica (eluent: CK2Cl2/MeOH 98/2) produces 74 mg {0.2 mmol, 55%) of 6 in the form of a white solid. Chemical formula: (Formula Removed) Rf - 0.5 (CH2Cl2/MeOH 95/5) 1H NMR (CDC13) : 7.68 (s, 1H, NH) ; 7.53 (d, J= 7.5 Hz, 1H, fill) ; 7.27 (d, J= 7.5 Hz, 1H, H-14) ; 7.20 (td, J = 7.5 Hz, J - 1.5 Hz, 1H, H-13) ; 7.14 (td, J = 7.5 Hz, J = 1.5 Hz, 1H, H-12) ; 6.61 (m, 1H, H-3) ; 4.64 (d, J = 2 Hz, 1H, H-5) ; 3.72 (s, 3H, CO2CH3) ; 3.63 (ddd, J = 14 Hz, J = 10 Hz, J- 5 Hz, 1H, H-7) ; 3.43 (ddd, J = 14 Hz, J = 5 Hz, J = 5 Hz, 1H, H-7) ; 3.32 (ddd, J = 17 Hz, J = 10 Hz, J = 5 Hz, 1H, H-8) / 3.01 (ddd, J = 17 Hz, J = 5 Hz, J= 5 Hz, 1H, H-8) ; 2.88 {m, 3H, H-2 and H-19) ; 2.81 (dd, J = 13 Hz, J - 2 Hz, 1H, H-l) ; 1.84 (dd, J = 18 Hz, J = 13 Hz, 3H, H-21) ; 1.81 (d, J = 13 Hz, 1H, H-l) . 13C NMR (CDC13) : 173.4 ; 143.3 (t, J = 28 Hz) ; 136.1 ; 135.3 132.1 (t, J - 9 Hz) ; 128.8 ; 122.1 ; 119.7