FR2668153A1 - NOVEL RIBONUCLEOSIDE COMPOUNDS, PROCESS FOR THEIR PREPARATION AND MEDICAMENTS CONTAINING SAME - Google Patents

Abstract

The compounds are of general formula (I) or (II) where Y is a group or an atom chosen from H, F, N3, dimethyldithiocarbamoyl (Me2NCSS) and diethyldithiocarbamoyl (Et2NCSS) and B is a natural or modified purine or pyrimidine base, excluding 4'-thio-2', 3'-didesoxy-2,6-diamino purine riboside and 4'-thio-2',3'-didesoxy cytidine and compounds of the above-mentioned general formula in which when Y is fluorine, B is pyrimidine. The compounds may be prepared, in particular, from L-arabinose, D-xylose or D-glucose. Application in antiviral, antitumoral and antibiotic drugs.

Description

 The present invention relates to novel compounds, process for their production and their applications.

 It is known that certain modified ribonucleosides possess interesting biological properties and that they are especially used as antibiotic, antiviral and antitumor agents.

 The antiretroviral activity of certain 2'-deoxyribonucleoside derivatives, such as 3'-azido-3'-deoxythymidine (AZT) or 3'-fluoro-3'-deoxythymidine (FLT), is attributable to the absence of hydroxyl 3 ', which inhibits the synthesis of proviral DNA produced by reverse transcriptase, an enzyme essential for the replication of the virus.

JB Kahlon et al. (summarized in Advances in Molecular
Biology and Targeted Treatments for AIDS, Xth International
Washington Spring Symposium in the Health Sciences,
Washington DC, May 15-18, 1990) presented two compounds, 4'-thio-2 ', 3'-dideoxy-2,6-diamino purine riboside and 4'-thio-2', 3'-dideoxy cytidine , as having a strong activity in vitro.

An object of the invention is to provide novel compounds, especially 2 ', 3'-dideoxy-B-derivatives.
D-ribonucleosides.

 Another object of the invention is to provide processes for the preparation of these compounds, which are of a simple implementation and which provide satisfactory yields.

 Yet another object of the invention is to provide such compounds which, by their biological properties, find a particularly advantageous application as antibiotic, antiviral and antitumor drugs.

où Y représente un groupe ou un atome choisis parmi: H, F, N31 diéthyldithiocarbamoyl (Et2NCSS), diméthyldithiocarbamoyl (Me2NCSS), et B représente une base de nature purique ou pyrimidinique, naturelle ou modifiée, à l'exclusion de la 4'-thio-2',3'-didésoxy-2,6-diamino purine riboside et de la 4'-thio-2',3'-didésoxy cytidine.The subject of the invention is therefore compounds of general formula

where Y represents a group or an atom chosen from: H, F, N31 diethyldithiocarbamoyl (Et2NCSS), dimethyldithiocarbamoyl (Me2NCSS), and B represents a base of purine or pyrimidine nature, natural or modified, excluding 4'- thio-2 ', 3'-dideoxy-2,6-diamino purine riboside and 4'-thio-2', 3'-dideoxy cytidine.

Preferably, B is selected from the following bases
uracil
thymine1
adenine,
guanine, cytosine,
5-fluorouracil,
2-thiouracil,
4-thiouracil,
hypoxanthine
5-iodouracil,
5-bromouracil,
5-chlorouracil, and
5- (2-bromovinyl) uracil.

The subject of the invention is also processes for preparing these compounds from carbohydrates, especially from
D-glucose;
D-xylose;
L-arabinose, or other appropriate carbohydrates.

 The invention also relates to the novel compounds obtained by the implementation of these methods.

First way: use of glucose.

Preferably, the conversion into the desired compound can be carried out according to the following steps:
a) protecting the hydroxyl groups in 1, 2, 5 and 6;
b) activation of the hydroxyl at 3;
c) hydrogenolysis of the substituent at 3;
d) selective deprotection of hydroxyls at 5 and 6;
e) protecting the hydroxyl group at 6;
f) activation of the hydroxyl at 5;
g) epoxy formation at 5.6;
h) formation of episulfide at 5.6;
i) opening of the episulfide
j) deprotection of the 1,2-hydroxyls;
k) oxidation;
1) deprotection, cyclization;
m) protecting the hydroxyls at 3 and 5;
n) condensation of a base B, purine or pyrimidine on anomeric position;
o) deprotection of the 3 'and 5'hydroxyls;
p) protection of the 5 'hydroxyl;
q) activation of the 3 'hydroxyl;
r) inversion of the 3 'hydroxyl configuration
s) activation of the 3 'hydroxyl;
t) introduction of the group Yen 3 ';
u) deprotection of hydroxyls and heterocyclic nitrogens.

 During step (a), the protection is preferably an R-CO-R 'ketone or an RCHO aldehyde in an acidic medium.

 The groups R and R 'represent in particular saturated or unsaturated alkyl radicals, substituted or unsubstituted by carbon groups or heteroatoms, or an unsaturated or unsaturated ring, which may or may not contain heteroatoms.

 The acid can be mineral or organic.

The mineral acid may be chosen in particular from HCl,
HBr, HBF4, H2S 4
The organic acid may be chosen in particular from
CH3COOH, CC13COOH, CF3COOH, p-CH3C6H4SO3H.

 During step (b), the OH group may in particular be replaced by a halide, by the action of a halogen in the presence of phosphine and nitrogenous base, or converted into sulfur ester. Each reaction must be conducted in a suitable solvent.

 The halide may be chosen in particular from: chlorine, bromine or iodine.

 The phosphine may especially be triphenylphosphine or tributylphosphine.

 The nitrogen base may be chosen in particular from: imidazole, pyridine, pyrimidine.

 The sulfur ester may be chosen in particular from: triflate, mesylate, tosylate, brosylate, nosylate, thiocarbonate, thiocarbamate, dithiocarbamate.

The solvent may be chosen in particular from organic solvents, such as: HMPA (hexamethylphosphoramide),
DMF (dimethylformamide), DMSO (dimethylsulfoxide), pyridine, CHCl3, ClCH2CH2Cl, CH2Cl2, CH3CN, ethyl acetate, aliphatic ether, aliphatic ketone, aromatic or aliphatic hydrocarbon, aliphatic alcohol, alone or in combination with solvents or other organic solvents.

 In step (c), the hydrogenolysis can be carried out either with a hydride in a non-protic anhydrous solvent or with hydrogen gas in the presence of a catalyst.

 The solvents used can be chosen from those defined in (b).

The hydride may be chosen in particular from LiAlH 4,
NaBH4, Et3SiH, Bu3SnH.

 The catalyst may be chosen in particular from: Raney nickel, palladium, rhodium, platinum black.

 In step (d), the deprotection of the hydroxyl groups at 5 and 6 is preferably in the presence of mineral or organic acid or acidic resins, in a suitable solvent.

 The acids can be chosen from those defined in (a).

 The solvent may be chosen from those defined in (b) and optionally mixed with water.

 In step (e), the protection of the hydroxyl at 5 is preferably carried out by esterification with a RCOC1 acid chloride or an anhydride (RCO) in the presence of organic base in a suitable solvent.

 The radical R represents in particular a group defined in step (a).

 The base may be an aromatic amine or not.

The solvent may be chosen from those defined in (b)
In step (f), the activation of the hydroxyl group is preferably carried out by esterification with a RSO2C1 sulfonic acid chloride or an anhydride (RSO2) 2 in the presence of organic base in a suitable solvent.

 For the synthesis of sulphonic esters, R may be chosen especially from: CH3, CF3, C6H5, p-CH3C6H4, p-BrC6H4, p-N02C6H41 imidasole.

 The solvent may be chosen from those defined in (b).

 The base may be an aromatic amine or not.

 In step (g), the epoxy formation at 5.6 preferably takes place in the presence of a mineral base such as an alkaline or alkaline earth hydroxide in a suitable solvent, or in the presence of an alkali alkoxide in a suitable solvent.

 The solvents are chosen in particular from those defined in (b) and optionally mixed with water.

 In step (h), the formation of episulfide in 5.6 may be carried out in the presence of a sulfur compound such as thioacetamide, an alkali thiocyanate or thiourea.

 This reaction takes place in a suitable solvent, chosen in particular from those defined in (b).

 In step (i), the opening of the 5.6 episulfide can be carried out in the presence of the alkaline carboxylate (RCOO-) and anhydride of the corresponding acid in a suitable solvent.

 The radical R represents in particular a group defined in step (a) and the solvent may be chosen from those also defined in step (b).

 During step (j), the deprotection of the hydroxyls at 1.2 can be carried out under the conditions already described in (d).

 In step (k), the oxidation can be carried out in particular by an alkaline periodate or periodic acid, in a suitable solvent.

 The solvent may be chosen from those defined in (b), optionally mixed with water.

 During step (1), the transformation may especially be carried out in the presence of a mineral or organic acid such as those defined in (a), in an appropriate solvent selected from those defined in (b).

 During step (m), the hydroxyl protection at 3 and 5 can be carried out in particular under the conditions defined in (d).

 The condensation step (n) with a purine or pyrimidine base can in particular be carried out in the presence of Lewis acid in a suitable solvent. The base may optionally be protected in the form of silylated ether or otherwise.

 The Lewis acid may be chosen in particular from: Ale13, AlBr3, AlF3, BF3 complex, transition metal triflate, trimethylsilyl triflate.

 The solvent may be chosen from those defined for step (b).

 Step (o) of deprotection of the hydroxyls 3 'and 5' can be carried out either in an acid medium or in a basic medium, in a suitable solvent.

 In acidic medium, the reaction can take place in a homogeneous medium or in a heterogeneous medium.

 In a homogeneous medium, conditions such as those described in steps (d) and (j) may be used.

 In a heterogeneous medium, the deprotection can be carried out in particular in the presence of ion exchange resin, in acid form, in solvents such as those defined in (b) and optionally mixed with water.

The step (p) of protecting the 5 'hydroxyl may be carried out in particular either by using a chloride of the ArAr'Ar "CCl type, or by using a chlorosilane of the type
RR'R "SiCl.

 The substituents Ar, Ar 'and Ar "represent in particular aromatic groups, the radicals R, R' and R" especially represent groups such as those defined in (a).

 Both types of reaction are carried out in a suitable solvent such as those defined in (b), in the possible presence of a nitrogenous base.

 The step (q) of activating the hydroxyl 3 'can be carried out under the conditions defined for (b).

 Step (r) can be performed under the conditions defined for (g).

 The step (s) of activation of the hydroxyl is preferably carried out under the same conditions as for (b).

The step (t) of introduction of the Y group with carbon-3 configuration inversion can be carried out in particular by the action of an alkaline salt of the Y ion when Y = N3, Me2CSS or Et2CSS, by action of a quaternary ammonium salt or a hydrofluoric acid complex when Y = F, finally under the conditions already defined in (c) when
Y = H.

 For all these reactions, the solvent may be chosen from those defined in (b).

 The final deprotection step (u) can be carried out either in an acid medium or in a basic medium, in a suitable solvent.

 In acidic medium, the reaction can take place in a homogeneous medium or in a heterogeneous medium.

 In a homogeneous medium, conditions such as those described in steps (d) and (j) may be used.

 In a heterogeneous medium, the deprotection can be carried out in the presence of ion exchange resin, in acid form, in a solvent such as those defined in (b) and optionally mixed with water.

 In basic medium, it is possible to use an alkali metal alcoholate in solution in the corresponding alcohol. The alcohol may be chosen in particular from: methanol, ethanol, isopropanol, isobutanol, benzyl alcohol.

Second way: use of D-xylose.

Preferably, the conversion into the desired compound is carried out according to the following steps:
a ') protecting the aldehyde group in position 1;
b ') protection of the hydroxyl groups in 2, 3, 4 and 5
c ') 1,2-dehydration and 3-deprotection;
d ') hydrogenation to 1,2;
e ') activation of position 3;
f ') introduction of the group Y at position 3;
g ') deprotection of the hydroxyl groups at 4 and 5;
h ') protecting the hydroxyl group at 5;
i ') activation of the position 4;
j ') change of the protective group of the function
aldehyde;
k ') epoxide formation in 4,5;
1 ') formation of episulfide in 4,5;
m ') opening of the episulfide;
n ') deprotection of the aldehyde and cyclization;
o ') condensation of a purine base or
pyrimidine on anomeric position;
p ') deprotection of hydroxyls and nitrogens
heterocyclic.

 During step (a '), the protection of the aldehyde function is preferably carried out by a RSH thiol in the presence of acid, in a suitable solvent.

 The radical R represents in particular a group defined in step (a).

 The solvent may be chosen from those defined in step (b).

 Step (b ') can be performed under conditions defined for step (a).

 In step (c '), the transformation is preferably under the action of a strong base in a suitable solvent.

 The base may be an alkali metal alcoholate.

The alcoholate may in particular be prepared from a primary alcohol ROH, secondary RCHOHR 'or tertiary (R) R'COHR "where R, R' and R" are radicals analogous to radical R described in (a)
The solvent used may be one or more solvents such as those defined in (b).

 Step (d ') is preferably carried out by the action of lithium aluminum hydride in a non-hydroxylated and anhydrous solvent.

 The solvent may be chosen in particular from organic solvents such as an ether, THF, dioxane or HMPA.

 Step (e ') can be performed under the conditions defined for step (b).

 Step (f ') can be performed under the conditions defined for step (t).

 Step (g ') can be performed under the conditions defined for step (d).

 Step (h ') can be performed under the conditions defined for step (e).

 During step (i '), the transformation is preferably carried out under the conditions already described in step (f).

 During step ('), the change of protective group of the aldehyde function can be achieved in particular by the action of an alcohol ROH in the presence of oxide and mercuric chloride.

 The radical R represents in particular a group defined in step (a).

 During step (k '), the formation of epoxide at 4.5 preferably takes place under the conditions defined in (g).

 During step (1 '), the formation of episulfide at 4.5 is preferably carried out under the conditions defined in (h).

 During step (m '), the opening of the episulfide at 4.5 is preferably carried out under the conditions defined in (i).

 The deprotection-cyclization step (n ') can be carried out in particular in the presence of a mixture of organic acid RCOOH and the corresponding anhydride, in the presence of a trace of strong acid.

 The group R represents in particular a group defined in step (a).

 The acid may especially be chosen from: HCl, H2SO4, p CH3C6H4SO3H.

 Step (o ') can be carried out under the conditions defined in (n).

 The final deprotection step (p ') can be carried out under conditions defined in (u).

Third way: use of L-arabinose.

Preferably, obtaining the desired product is carried out according to the following steps:
a ") protection of the aldehyde function;
b ") protection of the hydroxyl groups in 2, 3, 4 and 5
c ") 1.2 dehydration and 3 deprotection;
d ") 1,2-hydrogenation;
e ") introduction of the group Y at position 3;
f ") deprotection of the hydroxyl groups at 4 and 5;
g ") protecting the hydroxyl group at 5;
h ") activation of the hydroxyl at 4;
i ") change of protective group of the
fonctionaldéhydique;
j ") introducing a sulfur atom at the 4-position;
k ") deprotection of the aldehyde and cyclization;
1 ") condensation with a purine base or
pyrimidine on anomeric position;
m ") deprotection of hydroxyls and nitrogens
heterocyclic.

 Step (a ") can be performed under the same conditions as (a ').

 Step (b ") can be performed under the same conditions as (b ').

 Step (c ") can be carried out under the same conditions as (c ').

 Step (d ") can be performed under the same conditions as (d ').

 The step (e ") of introduction of the group Y with carbon-3 configuration inversion may in particular be carried out, when Y = N3, in the presence of azothydric acid or zinc azide, triphenylphosphine or tributylphosphine, and diethyl or diisopropyl azodicarboxylate in a suitable solvent.

 When Y = F, the reaction can be carried out in particular in a single step using diethylaminosulfur trifluoride (DAST) in a suitable solvent.

 For the other Y substituents, the transformation must be carried out in 2 steps under the conditions defined in (b) and (c) when Y = H, or using the conditions defined in (o) and (p) for the other substituents.

 In all cases, the solvent may be chosen from those defined in (b).

 Step (f ") can be performed under the same conditions as step (d).

Step (g ") can be carried out under the same conditions as step (e)
Step (h ") can be performed under the same conditions as step (f).

 Step (i ") can be carried out under the same conditions as step (j ').

 Step (j ") of indroduction of sulfur can be carried out for example using sodium thiolacetate in a suitable solvent selected from those defined in (b).

 The deprotection-cyclization step (k ") can be carried out under the same conditions as in step (n ').

 The condensation step (1 ") of the purine or pyrimidine base can be carried out under the same conditions as in step (n).

 The final deprotection step (m ") can be carried out under the same conditions as step (u).

This third path is preferred for its reduced number of steps compared in particular to the first path.

 The subject of the invention is also the novel intermediate compounds obtained in the processes according to the invention.

 The subject of the invention is also a medicinal product which may, in particular, be used as an antibiotic, antiviral and antitumor agent and comprising, as active ingredient, a compound as defined above.

 The invention will now be described in more detail using application examples of each of the methods described above.

First example: use of D-glucose.

 Step (a): 100 g of glucose monohydrate are dissolved in 2 l of acetone and then 60 g of concentrated sulfuric acid are added. The mixture is left at room temperature for 7 h and then neutralized with concentrated sodium hydroxide.

After filtration of the salt formed, the acetone is evaporated and the residue is extracted with toluene which can dissolve the 1,2: 5,6-di-O-isopropylidene-α-D-glucofuranose A at 100 g / l. The yield is 64% and the physical constants are in agreement with those of the literature.

 Step (b): 75 g of product A are dissolved in 1.5 liters of toluene together with 82.5 g of triphenylphosphine and 39 g of imidazole. The whole is brought to 80 ° C., then 79.5 g of finely ground iodine are added, the reaction mixture is maintained under reflux for 3 hours, then stirred, and then poured into 1 liter of saturated NaHCO 3 solution. The residue is taken up with 400 ml of a hexane-ether mixture to remove the triphenylphosphine oxide, which is filtered and, after evaporation of the filtrate, the crude product is purified on a silica column, dried over Na 2 SO 4, filtered and then evaporated. (Hexane eluent) The yield of pure 3-deoxy-1,2: 5,6-di-O-isopropylidene-3-iodo-α-D-allo-furanose B is 70% The physical constants are identical to those given in the litterature.

Step (c): 14.2 g of product B are dissolved in 350 ml of 95% ethanol and then 30 g of nickel are added.
Raney and 3 g of sodium acetate. The set is placed in a device to hydrogenate. After stopping the hydrogen consumption, the solution is evaporated to dryness. The residue is subjected to a water-chloroform partition. After decantation, the organic phase is dried over Na 2 SO 4, filtered and then evaporated. 3-Deoxy-1,2: 5,6-di-O-isopropylidene-ribohexofuranose C is isolated in a yield of 82%.

The physical constants are in agreement with those given in the literature.

 Step (d): 5.6 g of product C are dissolved in 100 ml of a 1: 1 v / v water-acetone mixture to which 1.7 ml of 50% tetrafluoroboric acid is added. After 5 hours, the solution is neutralized with triethylamine and filtered.

After evaporation, the residue is dissolved in ethyl acetate and then triturated with pentane. 3-Deoxy-1,2-O-isoprolydene-D-ribo-hexofuranose is isolated
Pure D with a yield of 92. mp 68-70 ° C; [?] - 13.22 (C = 1.1, chloroform).

 Step (e): 40.8 g of the product D are dissolved in 400 ml of pyridine maintained at -15 C. 31 g of benzoyl chloride are then added in 32 ml of chloroform and the mixture is stirred for 4 hours at 0 ° C. and 16 h at room temperature. The reaction mixture is poured into water. The organic phase is washed twice with water, dried over Na 2 SO 4, filtered and then evaporated. The residue is recrystallized from an ether-chloroform mixture. Pure 6-O-benzoyl-3-deoxy-1,2-isopropylidene-D-ribo-hexofuranose E is obtained with a yield of 78%. Mp = 136-137 ° C; [α] D 20 = -4.7 (c = 5, chloroform).

 Step (f): 28.75 g of the product obtained E are dissolved in 35 ml of pyridine, then 44.8 g of mesyl chloride dissolved in 170 ml of chloroform are added. The mixture is stirred for 18 hours at 40 ° C. The mixture is poured into water. The organic phase is washed twice with water, dried over Na 2 SO 4, filtered and then evaporated. The crude product is recrystallized from a pentane-chloroform mixture. 6-O-benzoyl-3-deoxy-1,2-O-isopro-pylidene-5-O-mesyl-α-D-ri bo-hexofuranose F is obtained in a yield of 90%.

= = 120-122C; [α] D20 = 18.6
Mp = 120-122 ° C; [α] D20 = 18.6 (c = 1, chloroform).

 Step (g): 38 g of compound F are dissolved in 280 ml of dichloromethane. A solution containing 5 g of sodium methanolate in 80 ml of methanol is then added dropwise, and the mixture is stirred for 24 hours at 0 ° C.

After evaporation of the solvent, the residue is purified on a silica column (pentane-CH 2 Cl 2 gradient). 5,6-Anhydro-3-deoxy-1,2-O-isopropylidene-L-lyxohefuranose G is obtained with a yield of 96%. 20 = -24 "
D
(c = 1.4, chloroform).

 Step (h): 14 g of the product G are dissolved in 600 ml of methanol, then 7 g of thiourea are added and stirring is maintained for 48 hours at room temperature.

The solvent is then evaporated and the residue obtained is dissolved in dichloromethane. This solution is washed with water, dried over Na 2 SO 4, filtered and then evaporated. 5,6-Thioepoxy3,5,6, -trideoxy-1,2-O-isopropylidene-D-ribo-hexofuranose
Pure H is obtained with a yield of 90%. [α] D22 = -51.79
D (c = 1.6, chloroform).

Step (i): 11.6 g of the product H are dissolved in a mixture containing 11.8 g of sodium acetate and 20 ml of acetic anhydride in 100 ml of acetic acid. The mixture is refluxed for 16 hours. The reaction mixture is poured into ice water and then extracted with dichloromethane. The organic phase is washed with saturated NaHCO 3 solution and then with water. After drying on
Na2SO4, filtration and evaporation, the residue is purified on a silica column (eluent dichloromethane). 6-O-acetyl-5-S-acetyl-5-deoxy-1,2-O-isopropylidene-5-thio-α-D-ribo-hexofuranose I is isolated in a yield of 74%. [α] D24 =
D 12.6 (c = 1.4, chloroform).

 Step (j): 10 g of product I are dissolved in 440 ml of a solution of 50% acetic acid in water. The mixture is then stirred for 24 h at 50 ° C. under a nitrogen atmosphere.

After evaporation of the solvent, the residue is dissolved in dichloromethane. The organic phase is neutralized, washed with water, dried over MgSO 4, filtered and then evaporated. The crude product is purified on a silica column (pentane-ethyl acetate gradient). 6-O-acetyl-5-acetyl-3,5-dideoxy-5-thio-ribohexofuranose J is obtained with a yield of 80%; D = -21.24 (c = 1.2, chloroform).

 Step (k): 6.4 g of product J are dissolved in 100 ml of methanol. A solution of 5.16 g of NaIO4 in 100 ml of water is then added. The mixture is stirred for 1 hour at 10 ° C. The mixture is extracted with dichloromethane. The organic phase is dried over MgSO 4, filtered and evaporated at low temperature. The crude 5-O-acetyl-4-S-acetyl-2,4-dideoxy-4-thio-aldehyde-D-erythro-pentose K is used directly for the next step.

Step (1): Product K is dissolved in 125 ml of 0.25% HCl methanol solution. The mixture is stirred for 24 hours at room temperature. After evaporation of the solvent, the residue is purified on silica (pentane-ethyl acetate gradient). The yield of methyl 2, 4-dideoxy-4-thio-D-erythro-pentofuranoside L is 60% relative to the product J. 22 = -52 (c = 1.1;
LcxJD chloroform).

 Step (m): 5 g of the product J are dissolved in 80 ml of pyridine at 0 ° C. 12 g of paramethylbenzoyl chloride are then added and the whole is kept at ambient temperature for 16 hours. At the end of this time, the mixture is poured into water and then extracted with chloroform. The reaction is then carried out as in step (e). The yield of methyl 2, 4-dideoxy-3,5-di-O- (paramethylbenzoyl) -4-thio-D-erythro-pentofuranoside M is 70%. M.p. 72-74 ° C.

 Step (n): 1.3 g of the product M, O, 43 g of thymine, 1.6 ml of trimethylsilyl triflate, 1.3 ml of chlorotrimethylsilane, 0.5 ml of hexamethyldisilazane are dissolved in 35 ml of acetonitrile and refluxed for 12 h. At the end of this time, 20 ml of dichloromethane are added and the mixture is washed with a saturated aqueous solution of NaHCO 3. After drying over MgSO 4 and filtration, the organic phase is evaporated and the residue is purified on a silica column (gradient dichloromethane-ethyl acetate). The yield of 4'-deoxy-3 ', 5'-di-O- (paramethylbenzoyl) -4-thio-thymidine N is 40%.

Step (o): 1.3 g of the product N is dissolved in a solution obtained by reaction of 0.02 g of sodium in
100 ml of methanol. After 5 h at room temperature, the solution is neutralized by adding DOWEX 50W-X8 acidic resin. After filtration, the solution is evaporated under high vacuum and the residue is recrystallized from an acetone-toluene mixture. The yield of 4'-deoxy-4'-thiothymidine
O is 908.

 Step (p): 6.9 g of the product 0 and 9 g of trityl chloride are dissolved in 50 ml of pyridine containing 0.1 g of dimethylaminopyridine. The mixture is heated at 80 ° C for 30 minutes and then cooled to 0 ° C.

 Step (q): To the solution obtained in (p), 3.6 g of methanesulfonyl chloride are added and the whole is kept for 12 hours at 5 ° C. At the end of this time, the mixture is poured into water. water and the solid which precipitates is wrung out.

The crude 4'-deoxy-3'-O-mesyl-4'-thio-5'-O-trityl-thymidine is used directly for further reactions.

 Step (r): the product Q is dissolved in 110 ml of 90% methanol containing 2.12 g of sodium hydroxide. The mixture is refluxed for 2 h and then, after cooling, the medium is acidified with 809E acetic acid. The precipitate formed is drained, then washed with water and dried in an oven. After purification on a silica column (hexane-ethyl acetate gradient), the yield of 1- (2 ', 4'-di-deoxy-4'-thio-51-O-trityl-ss-D-lyxofuranosyl) thymine R is 58% relative to the product O. mp = 146-148 ° C.

 Step (s): To a solution of 3 g of the product R in 30 ml of pyridine is added 1.14 g of methanesulfonyl chloride, and then left for 12 hours at 5 ° C. At the end of this time, mixture is treated as in step (q).

The yield of 1- (2 ', 4'-dideoxy-3'-O-mesyl-4'-thio-5'-O-trityl-ss-D-lyxofuranosyl) thymine S is 83%. Mp 170-171 ° C.

Step (t): the crude product S is dissolved in 50 ml of anhydrous DMF, then 0.7 g of LiN 3 is added and the mixture is heated.
1 h at 80 ° C. The solvent is then evaporated under high vacuum and 3'-azido-3 ', 4'-dideoxy-4'-thio-5'-O-trityl-thymidine
Gross T is used directly for the next step.

Step (u): The product T is heated with 20 ml of 80% acetic acid for 20 minutes. After evaporation of the solvent and purification on a silica column (hexane-ethyl acetate gradient), pure 3'-azido3 ', 4'-dideoxy-4'-thio-thymidine U is obtained with a yield of
14% relative to the product O. F = 134-135 ° C; [a] 22 = 87 "(c
D - = 0.5; water)
Remarks:
1) In step (t), replacing the lithium azide with tetrabutylammonium fluoride gives 3'-fluoro-3 ', 4'-dideoxy-4'-thio-5'-O-trityl T1 thymidine.

After treatment under the conditions of (u), 3'-fluoro-3 ', 4'-dideoxy-4'-thiothymidine U1 is isolated in a yield of 17% relative to product O.

 2) In step (t), replacing the lithium azide with lithium dimethyldithiocarbamate, there is obtained 3 '- (N-dimethyldithiocarbamoyl) -3', 4'-dideoxy-4'-thio-5 ' After treatment under the conditions of (u), 3 '- (N-dimethyldithiocarbamoyl) -3', 4'-dideoxy-4'-thiothymidine U2 is isolated in a yield of 15% by weight. report to the product O.

 3) In step (t), replacing the lithium azide with lithium diethyldithiocarbamate, there is obtained 3 '- (N-diethyldithio-carbamoyl) -3', 4'-dideoxy-4'-thio- 5'-O-trityl-thymidine T3. After treatment under the conditions of (u), 3 '- (N-diethyldithio carbamoyl) -3', 4'-dideoxy-4'-thiothymidine U3 is isolated in a yield of 14% relative to the product o .

4) In step (t), treating the compound
S with tributyltin hydride in the presence of AIBN (azobisisobutyronitrile) gives 3 ', 4'-dideoxy-4'-thio-5-O'-tritylthymidine T4. After treatment under the conditions of (u), 3 ', 4'-dideoxy-4'-thiothymidine U4 is isolated in a yield of 12% relative to product O.

Second example: use of D-xylose.

 Step (a '): 30 g of D-xylose are dissolved in 45 ml of isobutanethiol at 0 ° C., then 40 ml of concentrated hydrochloric acid are added and the mixture is stirred for 30 minutes at room temperature. At the end of this time, the solvent is evaporated to the maximum and the aqueous phase is extracted with dichloromethane.

The organic phase is washed with water, dried over MgSO4, filtered and then evaporated. A colorless syrup is obtained which does not require purification. The yield of diisobutyldithioacetal of D-xylose A 'is 92%; [α] D27 = 64.6 "(c = 1.2, chloroform).

 Step (b '): 30 g of the product A' are dissolved in 300 ml of acetone at 0 ° C. and then 4.5 ml of concentrated H 2 SO 4 are added. Stirring is then continued for 16 hours at room temperature. At the end of this time, the mixture is poured into water and extracted with dichloromethane. The organic phase is washed several times with water, dried over MgSO 4, filtered and then evaporated. Di-isobutyldithioacetal was isolated from pure 2,3: 4,5-di-O-isopropylidene-D-xylose B 'with 70% yield; Cl127 = -22.94 ° (c = 1.2, chloroform).

Step (c '): 7 g of the product B' are dissolved in 60 ml of anhydrous THF and the solution is added to a mixture of 3 g of potassium t-butanolate dissolved in 150 ml of
THF and 50 ml of DMSO. The mixture is stirred for 3 h at room temperature. At the end of this time, the solution is concentrated and the desired product is extracted with pentane.

After filtration on silica, the solvent is evaporated. The yield of di-isobutyldithioacetal of 2-deoxy-1,2-didehydro-1-en-4,5-O-iso-propylidene-D-xylose
It is 65%; 27 = -6.33 (c = 1.3, chloroform).

 Step (d '): to a suspension of 3.77 g of LiAlH4 in 250 ml of anhydrous ethyl ether is added a solution of 7r31 g of the product C' in 80 ml of ethyl ether. The mixture is stirred for 3 h and then poured into a dilute hydrochloric acid solution. The organic phase is decanted, dried over MgSO4, filtered and then evaporated. D-isobutyldithioacetal is isolated from pure 2-deoxy-4,5-O-isopropylidene-D-threo-pentose with 90% yield.

 [?] = 10.61 (c = 1.1, chloroform).

D
Step (e '): 31 g of the product D' are dissolved in 60 ml of pyridine at 0 ° C., then 12 g of methanesulfonyl chloride are added. Stirring is continued for 2 hours at room temperature. The mixture is then poured into water and extracted with dichloromethane. After washing the organic phase with a dilute HCl solution and then with water until neutral pH, it is dried over MgSO 4. After filtration and evaporation, the residue is purified on silica (pentane-ethyl acetate gradient). 2-Deoxy-3-O-mesyl-4,5-O-isopropyl-idene-D-threo-pentose di-isobutyl-dithioacetal is obtained with a yield of 80%; [α] 28 = 1.7 (c = 1.4, chloroform).

 Step (f '): 30 g of the product prepared in E' are dissolved in a solution of 31 g of lithium azide in 250 ml of anhydrous DMF. Everything is heated at 100 C for 12 hours. At the end of this time, the mixture is poured into water and then extracted with dichloromethane. After drying the organic phase over MgSO 4, filtration and evaporation, the residue obtained is purified on a silica column (pentane-ethyl acetate gradient).

The yield of di-isobutyl-dithioacetal of 3-azido-2,3-dideoxy-4,5-O-isopropyl-diene-D-erythro-pentose
F 'is 8426. 22 = -9.47 "(C = 1.2, chloroform).

 Step (g '): 26 g of the product F' are dissolved in 60 ml of 95W ethanol, and then the solution is passed for 4 hours on 250 ml thermosate jacket at 50 C filled with 140 g of acidic resin in suspension in 180 ml of the same solvent. After evaporation of the solvent, di-isobutyl-dithioacetal was isolated from ss-azido-2,3-dideoxy-D-erythro-pentose G 'with 86% yield.

Step (h '): 20 g of the product G' are dissolved in 125 ml of pyridine at -10 ° C., and 8.8 g of benzoyl chloride in solution in 10 ml of chloroform are then added. The mixture is stirred for 4 h at 0 ° C. and then for 16 h at room temperature. At the end of this time, the whole is poured into water and then extracted with dichloromethane. The organic phase is then washed with dilute hydrochloric acid and then with water until neutral pH. After drying over MgSO 4, filtration and then evaporation, the residue obtained is purified on a silica column (pentane-ethyl ether gradient). The yield of diisobutyldithioacetal of 3-azido-5-O-benzoyl 2,3-dideoxy-D-erythro-pentose H 'is 51%; [a] 27 = i
D 0.60 (c = 0.8, chloroform).

 Step (i '): 15 g of the product H' are dissolved in 30 ml of pyridine at 0 ° C., then, after adding 5 g of methanesulfonyl chloride, the reaction is carried out as in (e '). The desired 3-azido-5-O-benzoyl-2,3-dideoxy-4-O-mesyl-D-erythro-pentose di-isobutyldithioacetal is obtained in 85% yield. [α] D24 = 25 (c = 1.3, chloroform).

 Step (j '): 15 g of the I' are dissolved in 150 ml of methanol, then 36 g of mercuric oxide and 22.6 g of mercuric chloride are added. The mixture is stirred for 2 hours at 60 ° C. and then filtered on celite.The residue is washed with methanol and the filtrates are combined and concentrated before the addition of chloroform.This organic phase is successively washed with a 1% KI solution. mole / l, dried over MgSO 4 and finally evaporated The desired 3-azido-5-O-benzoyl-2,3-dideoxy-4-O-mesyl-D-erythro-pentose dimethyl acetal is obtained in a yield of 70%. %.

 Step (k '): To a solution of 10 g of the product J' in 90 ml of chloroform at 0 ° C. is added a solution of 1.6 g of sodium methanolate in 25 ml of methanol. The mixture is maintained for 24 h at 0 ° C. and then treated as in step (g). The dimethyl acetal of 4,5-anhydro-3-azido 2,3-dideoxy-L-threo-pentose K 'is obtained in a yield of 75%; [α] D20 = -0.11 (c = 1.2, chloroform).

 Step (1 '): A mixture of 4 g of product K' and 1.63 g of thiourea in 50 ml are treated as in step (h). The desired 3-azido2,4,4,5-tetradésoxy-475-thioepoxy-D-erythropentose dimethylacetal is obtained in a yield of 90%.

 Step (e-): A mixture of 3 g of the product L 'and 2.4 g of sodium acetate is dissolved in 5.5 ml of acetic acid and 28 ml of acetic anhydride. The reaction is then carried out as in step (i). After purification, dimethylacetal was isolated from 3-azido-5-O-acetyl-4-S-acetyl-2,3,4-trideoxy-4-thio-D-erythro-pentose M 'with a yield of 76%.

Step (n '): 0.5 g of the product M' is dissolved in a solution containing 3 ml of acetic acid, 3 ml of acetic anhydride and 0.1 ml of sulfuric acid. The whole is maintained for 1 h at 0 ° C. At the end of this time, the mixture is poured into water and then extracted with chloroform. After being successively washed with a 1 mol / l solution of NaHCO 3 and then with water, the organic phase is dried over MgSO 4, filtered and then evaporated. The residue obtained is purified on a silica column (pentane-ethyl acetate gradient). 3-Azido-1,5-di-O-acetyl-4-thio-2,3,4-trideoxy
D-erythro-pentofuranose N 'is isolated with a yield of 70%.

Step (o '): 0.6 g of the product N', 0.31 g of 2-thiouracil, 0.2 ml of chlorotrimethylsilane, 0.35 ml of
HMDS and 0.45 ml of trimethylsilyl triflate are dissolved in 10 ml of 1,2-dichloroethane. The mixture is heated for 3 h at 60 ° C. under a nitrogen atmosphere, 20 ml of dichloromethane are then added and the mixture is then washed with a saturated aqueous solution of NaHCO.sub.3 After decantation, drying over MUSO4 and filtration, the organic phase is evaporated. The residue is purified on a silica column (pentane-ethyl acetate gradient) The yield of 5'-O-acetyl-3'-azido-2 ', 3'-14'-trideoxy-2,4'-dithio- Uridine O 'is 40%.

 Step (p '): the product O' is treated under conditions identical to those described in (u) Isolation after reaction 3'-azido-2 ', 3', 4'-trideoxy2,4'-dithiouridine P 'desired with a yield of 88%. Mp = 127-129 ° C, cor128 = 91 (c = 0.4, water).

D
Remarks:
1) In step (f '), replacing the lithium azide with tetrabutylammonium fluoride, is obtained the di-isobutyldithioacetal of 3-fluoro-2,3-dideoxy-4,5-isopropylidene-D- erythro-pentose F '. After treatment under the conditions of steps (g ') to (p'), 3'-fluoro-2 ', 3', 4'-trideoxy-2,4'-dithiouridine P1 is isolated.

 2) In step (f '), replacing the lithium azide with lithium dimethyldithiocarbamate, the 3- (N-dimethyldithiocarbamoyl) -2,3-dideoxy-4,5-O-diisobutyldithioacetal is obtained isopropylidene-D-erythro-pentose F2.

After treatment under the conditions of steps (g ') to (p'), 3 '- (N-dimethyldithio-carbamoyl) -2', 3 ', 4'-tridoxy-2,4'-dithio-uridine P2 is isolated. .

 3) In step (fl) r, replacing the lithium azide with lithium diethyldithiocarbamate, 3- (N -diethtyldithiocarbamoyl) -2,3-dideoxy-4,5-O-isopropylidene diisobutyldithioacetal is obtained. -D-erythro-pentose F '.

3
After treatment under the conditions of steps (g ') to (p'), 3 '- (N-diethyldithio-carbamoyl) -2', 3 ', 4'-tridoxy-2,4'-dithiouridine P3 is isolated. .

 4) In step (f '), by treating the compound E' with lithium aluminum hydride, 2,3-dideoxy-4,5-O-isopropylidene-D-erythro-di-isobutyldithioacetal is obtained. penthose F4. After treatment under the conditions of steps (g ') to, 2', 3 ', 4'-trideoxy-2,4'-dithiouridine Po is isolated.

Third example: use of L-arabinose.

Step (a "): 20 g of L-arabinose are dissolved in 18 ml of ethanethiol at 0 ° C., then 25 ml of concentrated hydrochloric acid are added, the mixture is kept for 1 hour at 0 ° C. and the reaction is then treated in Same conditions as in step (a ') The diethyldithioacetal of L-arabinose A "is obtained with 90% yield. F = 102-104 ° C; [α] 22 = 11.21
D (c = 1,2, methanol).

 Step (b "): To a solution of 25 g of the product A" in 300 ml of acetone at 0 ° C. are added 3.8 ml of H2SO4. The reaction is then continued under the conditions of step (b '). The diethyl dithioacetal of 2,3: 4,5-di-O-isopropylidene-L-arabinose B "was obtained with 61% yield, 26 = -72.36 ° (c = 1.2, chloroform).

D
Step (c "): To 9 g of the product B" dissolved in 90 ml of THF is added a solution of 4.5 g of potassium t-butanolate dissolved in 225 ml of THF and 75 ml of DMSO.

The reaction is then continued under the conditions of step (c '). The yield of 1,2-dideoxy-1,2-didehydro-1-en-4,5-O-iso-propylidene diethyldithioacetal
L-arabinose C is 65%.

 Step (d "): To a suspension of 3.8 g of LiAlH 4 in 250 ml of anhydrous ethyl ether is added a solution of 6 g of the product C" in 80 ml of anhydrous ethyl ether. After stirring for 4 hours at room temperature, the reaction is continued under the conditions of stage (d ').

The yield of diethyldithioacetal of 2-deoxy-4,5-O-isopropylidene-L-erythro-pentose D "is 82% [] 26 = -11.76 (c = 1.6, chloroform).

Step (e "): A mixture of 5.6 g of product D", 4.6 g of zinc azide and 10.5 g of triphenylphosphine is placed in 100 ml of benzene. 8 ml of diisopropyl azodicarboxylate are then added dropwise with stirring. Stirring is continued for 12 h at room temperature. At the end of this time, the solution is filtered on celite, then evaporated and the residue is purified on a silica column (pentane-ether gradient). The yield of diethyldithioacetal of 3-azido-2,3-dideoxy-4,5-O-isopropylidene-L-threo-pentose
E "is 75 g, [α] D26 = -6.66 (c = 1.2, chloroform).

Step (f "): 14 g of the product E" are dissolved in
100 ml of 95% ethanol and the reaction is continued as in step (g '). The yield of diethyldithioacetal of 3-azido-2,3-dideoxy-L-threo-pentose F "is 96%.

 Step (g "): 10 g of the product F" are dissolved in 80 ml of pyridine at 0 ° C. A solution of 5.4 g of benzoyl chloride in 8 ml of chloroform is then added. The reaction is then continued under the conditions defined in step (h '). The desired 3-azido-5-O-benzoyl-2,3-dideoxy-L-threo pentose G "diethyl dithioacetal was isolated with 60% yield. [& Alpha] D24 = 5.77 (c = 1.3; chloroform).

D
Step (h "): 5 g of the product G" are dissolved in a mixture of 1.5 g of triethylamine and 10 ml of dichloromethane at 0 ° C. 2 g of methanesulfonyl chloride are then added, followed by stirring for 2 hours. h at room temperature. The reaction is then continued under the conditions of step (e '). The yield of diethyldithioacetal of 3-azido-5-O-benzoyl-2,3-dideoxy-4-O-mesyl-L-threo-pentose H "is 96%;
D -16.9 (c = 1.2, chloroform).

 Step (i "): 5.9 g of the above product are dissolved in 80 ml of methanol, then 13.2 g of mercuric oxide and 11.3 g of mercuric chloride are added, the reaction is then continued under the conditions of Step (d) The yield of dimethyl acetal of 3-azido-5-O-benzoyl-2,3-dideoxy-4-O-mesyl-L-threo-pentose I - is 95%.

Step (j "): 0.5 g of the product I" are dissolved in a solution of 0.8 g of sodium thiolacetate in 10 ml of
DMF. The whole is heated at 100 ° C. for 2 hours and the reaction is then continued under the conditions of step (f ') .The yield of dimethylacetal of 3-azido-5-O-benzoyl-4-S acetyl -4-thio-2,3,4-trideoxy-D-etythro-pentose J "is 64%.

 Step (k "): 0.5 g of the product J" is treated under the conditions of step (n '). The desired 1-O-acetyl-3-azido-5-O-benzoyl-2,3,4-trideoxy-4-thio-erythro-pentofuranose is obtained in 68% yield. It can be used for steps (1 ") and (m") under the same conditions as the product obtained in (n ') is used for steps (o') and (p ').

Remarks:
1) In step (e "), treating the compound D" with diethylaminosulfur trifluoride (DAST) gives the diethyldithioacetal of 2,3-dideoxy-3-fluoro-4,5-O-isopropylene-L -threo-pentose E'1 with a yield of 55%.

 2) In step (e "), treating the compound D" successively with methanesulfonyl chloride, then with lithium dimethyldithiocarbamate under the conditions of (h "), the 2,3-dideoxy diethyldithioacetal is obtained. 3 (N-dimethyldithio-carbamoyl) -4,5-O-isopropylidene-L-threo-pentose E2 with a yield of 46% relative to product D ".

 3) In step (e "), treating compound D" successively with methanesulfonyl chloride and then with lithium diethyldithiocarbamate under the conditions of (h "), the 2,3-dideoxy diethyldithioacetal is obtained. 3 (N-diethylidithiocarbamoyl) -4,5-O-isopropylidene-L-threo-pentose E3 in 47% yield relative to product D ".

 4) In step (e "), treating the compound D" successively under the conditions of (b) and (c), the diethyldithioacetal 2,3-dideoxy-4,5-O-isopropylidene-L is obtained threo-pentose E4 with a yield of 508 relative to compound D ".

 The compounds according to the invention are preferably packaged in doses of 100 to about 1000 mg, preferably of the order of 500 mg, especially in the form of capsules for the oral route.

Claims (18)

 1. Compounds corresponding to the following general formula

 wherein Y represents a group or an atom selected from H, F, N3, dimethyldithiocarbamoyl (Me2NCSS) and diethyldithiocarbamoyl (Et2NCSS) and B represents a base of purine or pyrimidine nature, natural or modified, excluding 4'- thio-2 ', 3'-dideoxy-2,6-diamino purine riboside and 4'-thio-2', 3'-dideoxy cytidine.  5- (2-bromovinyl) uracil.  5-chlorouracil, and  5-bromouracil,  5-iodouracil  hypoxanthine  4-thiouracil,  5-fluorouracil, 2-thiouracil,  guanine, cytosine,  adenine,  thymine  uracil  2. Compounds according to claim 1, characterized in that B is chosen from the following bases  3. Process for the preparation of compounds according to claim 1 or 2, characterized in that one starts from L-arabinose, D-xylose or Glucose.  4. Method according to claim 3, characterized in that, starting from L-arabinose, the following steps are carried out  a ") protection of the aldehyde function  b ") protecting the hydroxyl groups in 2, 3, 4 and 5;  c ") dehydration in 1,2 and deprotection in 3  d ") hydrogenation in 1,2  e ") introduction of group Y, defined in  claim 1 in position 3  f ") deprotection of the hydroxyl groups at 4 and 5  g ") protecting the hydroxyl group in 5  h ") activation of the hydroxyl in 4  i ") change of the protective group of the function  aldehyde  j ") introduction of a sulfur atom in position 4  k ") deprotection of the aldehyde and cyclization  l ") condensation with a purine base or  pyrimidine on anomeric position  m ") deprotection of hydroxyls and nitrogens  heterocyclic.  5. Method according to claim 3, characterized in that, starting from D-xylose, the following steps are carried out  a ') protection of the aldehyde group in position 1  b ') protection of the hydroxyl groups in 2, 3, 4 and 5  c ') dehydration in 1, 2 and deprotection in 3  d) Hydrogenation in 1, 2  e ') activation of position 3  f ') introduction of group Y, defined in  claim 1 in position 3  g ') deprotection of the hydroxyl groups at 4 and 5  h ') protecting the hydroxyl group in 5  i ') activation of position 4  j ') change of the protective group of the function  aldehyde  k ') epoxide formation in 4, 5  1 ') formation of episulfide in 4, 5  m ') opening of the episulfide;  n ') deprotection of the aldehyde and cyclization  o ') condensation of a purine or pyrimidine base  in anomeric position  p ') deprotection of hydroxyls and nitrogens  heterocyclic.  6. Method according to claim 3, characterized in that, starting from D-glucose, the following steps are carried out  a) protecting the hydroxyl groups in 1, 2, 5 and 6;  b) activation of the hydroxyl in 3  c) hydrogenolysis of the substituent in 3  d) selective deprotection of 5 and 6 hydroxyls  e) protection of the hydroxyl group in 6  f) activation of the hydroxyl in 5  g) epoxide formation in 5, 6  h) formation of episulfide in 5, 6  i) opening of the episulfide  j) deprotection of the hydroxyls in 1, 2  k) oxidation  1) deprotection, cyclization  m) protection of the hydroxyls in 3 and 5  n) condensation of a purine base or  pyrimidine on anomeric position  o) deprotection of hydroxyls in 3 'and 5'  p) protection of the hydroxyl in 5 '  q) activation of the hydroxyl in 3 '  r) reversal of the 3 'hydroxyl configuration;  s) activation of the hydroxyl in 3 '  t) introduction of group Y in 3 '  u) deprotection of hydroxyls and nitrogens  heterocyclic.  7. New compounds obtained by the implementation of the method according to any one of claims 3 to 6.  8. Compound according to one of claims 1, 2 and 7, characterized in that it is 3'-azido-3 ', 4'-dideoxy-4'-thio-thymidine.  9. Compound according to one of claims 1, 2 and 7, characterized in that it is 3'-fluoro-3 ', 4'-dideoxy-4'-thio-thymidine.  10. Compound according to one of claims 1, 2 and 7, characterized in that it is 3 '- (N-dimethyldithiocarbamoyl) -3'-4'-dideoxy-4'-thiothymidine.  11. Compound according to one of claims 1, 2 and 7, characterized in that it is 3 '- (N-diethyldithiocarbamoyl) -3', 4'-dideoxy-4'-thiothymidine.  12. Compound according to one of claims 1, 2 and 7, characterized in that it is 3 ', 4'-dideoxy-4'-thio-thymidine.  13. Compound according to one of claims 1, 2 and 7, characterized in that it is 3'-azido-2 ', 3', 4'-trideoxy-2,4'-dithiouridine .  14. Compound according to one of claims 1, 2 and 7, characterized in that it is 3'-fluoro-2 ', 3', 4'-trideoxy-2,4'-dithiouridine .  15. Compound according to one of claims 1, 2 and 7, characterized in that it is 3'- (Ndimethyldithio-carbamoyl) -2 ', 3', 4'-trideoxy-2,4 ' -dithiouridine.  16. Compound according to one of claims 1, 2 and 7, characterized in that it is 3 '- (Ndiéthyldithio-carbamoyl) -2', 3 ', 4'-trideoxy-2,4' -dithiouridine  17. Compound according to one of claims 1, 2 and 7, characterized in that it is 2 ', 3', 4'-triideoxy-2,4'-dithio-uridine.  18. A medicinal product which may be used in particular as an antibiotic, antiviral and antitumor agent, characterized in that it contains, as active ingredient, a compound defined in one of claims 1, 2 and 7 to 17.