ES2220226A1 - Stereoselective method of preparing gamma-amino vinyl sulphones - Google Patents

Abstract

The invention relates to a stereoselective method of preparing gamma -amino vinyl sulphones. The inventive method comprises: the reaction of the corresponding N-protected (1-aminoalkyl) epoxide with a thiol, or an alkaline metal salt thereof oxidation of the sulphur obtained to form sulphone and subsequent dehydration in order to obtain, separately, either of the two enantiomers of the gamma -amino vinyl sulphone having formula (I). The method can also be used equally simply to obtain both enantiomers of a determined gamma -amino vinyl sulphone in high yields and with good optical purity. The invention also relates to novel intermediates which are used in the aforementioned preparation method and some substantially-pure novel enantiomers of said gamma -amino vinyl sulphones. Moreover, the enantiomers of the gamma -amino vinyl sulphones can be used as intermediates in the preparation of pharmaceuticals based on peptidyl vinyl sulphones. R1-CH[N(GP)(GP')]-CH=CH-SO2-R2 (I)

Description

Stereoselective procedure for preparing γ-amino vinyl sulfones.

This invention relates to a process. stereoselective for the preparation of γ-amino vinyl sulfones, whose enantiomers they are useful as intermediates for the preparation of peptidyl vinyl sulfones, as well as new intermediates useful in said Preparation procedure

Prior art

Cysteinyl proteases are a subclass of proteolytic enzymes that can be found in viruses, bacteria, protozoa, fungi, plants and mammals. The spectrum of biological activity of these enzymes is very wide: they are involved in the cellular turnover of mammals and in apoptosis, in the process of replication of the human rhinovirus and in the life cycle of many parasites. The inhibition of cysteinyl proteases is therefore an important strategy for the development of new drugs for the treatment of tumors, inflammatory diseases, viral infections (for example, the common cold) and for infections by protozoa and bacteria (for example, malaria, Chagas disease or leishmaniasis). In 1995, researchers at "Khepri Pharmaceuticals" described for the first time the use of certain peptidyl vinyl sulfones as potent and selective inhibitors of cysteinyl proteases (cf. eg JT Palmer et al., J. Med. Chem . 1995, vol 38, pp. 3193-3196; D. Brómme et al, Biochem . J. 1996, vol. 315, pp. 85-89). Further research led to the development of a peptidyl vinyl sulfone inhibitor of falcipain whose in vivo evaluation showed that it clearly delayed the progression of malaria in murides (cfr. Eg JE Olson et al., Bioorg. Med. Chem . 1999, vol. 7 , pp. 633-638; KA Scheidt et al., Bioorg. Med. Chem . 1998, vol. 6, pp. 2477-2494). It has also been established that peptidyl vinyl sulfones are useful as proteasome inhibitors and their bacterial counterpart HsIVU. The following compounds are representative examples of inhibitors of the peptidyl vinyl sulfone type.

one

Despite their biomedical relevance, the procedures for preparing the necessary γ-amino vinyl sulfones in enantiomerically pure form are very limited, and are based without exception on stereospecific transformations of non-racemic chiral α-amino acids (cf. eg JT Palmer et al., J. Med. Chem . 1995, vol 38, pp. 3193-3196; S. Sengupta et al., Tetrahedron Asymmetry 1998, vol. 9, pp. 2311-2316). Specifically, these procedures involve the preparation of either α-amino aldehydes (a type of compounds that generally readily racemize) or of amino-diazoketone amines (whose industrial scale handling is difficult). Therefore, the processes for preparing γ-amino vinyl sulfones known in the state of the art are difficult to scale and are seriously limited in terms of the structure of the final products. Therefore, the contribution of an alternative process for the preparation of γ-amino vinyl sulfones in N-protected form, which is short and efficient (that is to say that it takes place with high yields and that leads to products of high optical purity), It is interesting for the industrial manufacture of drugs based on peptidyl vinyl sulfones.

Description of the invention

According to one aspect of the present invention, provides a stereoselective procedure for the manufacture of a substantially pure enantiomer of a γ-amino vinyl sulfone of formula (I), alternatively (I '), which comprises a dehydration step of a β-hydroxy-γ-amino  sulfone of formula (II), alternatively (II '),

two

where:

in formulas (II) and (II '), the lines wavy means any of the two possible chiral carbon configurations to which they are attached;

R 1 is a radical selected from the group consisting of: (C 1 -C 6) -alkyl, (C 3 -C 6) -cycloalkyl, [(C 1 -C_ {6}) alkyl-
nylsilyloxy] - (C, -C 6) -alkyl, [(C 1 -C 6)-trialkylsilyloxy] - (C 1 -C 6) -alkyl, (C 1) -C 4) - alkoxy, GP-O- (CH 2) n, naphthyl, phenyl, Ph- (CH 2) n -, R-COO- (CH 2 ) n - where R (C 1 -C 6) -alkyl or phenyl, and a radical derived from the aforementioned mentioned with benzene rings through a mono- or a di-substitution in their rings benzene, the substituents being a radical independently selected from the group consisting of: halogen, (C 1 -C 4) -alkyl, (C 1 -C 4) -alkoxy, trifluoromethyl, an amino group protected and a protected hydroxyl;

R2 is a radical selected from it group than R 1, further including phenylcarbonyl;

n is an integer selected from 1 to 10; and GP represents an amine protecting group; GP 'represents an atom of hydrogen or an amine protecting group equal to or different from GP; or alternatively, GP and GP 'taken together form a group phthalimido

In a preferred embodiment of the invention, the compounds of formula (II), alternatively (II '), are those where the protective group GP is selected from the group formed by carbamates, amides and sulfonamides and, GP 'is an atom of hydrogen or a protective group selected from the same group as GP, also including an allyl, a benzyl and a mono benzyl or di-substituted. In a more preferred embodiment of the invention, the protective group GP is selected from the group formed by t-butoxycarbonyl (BOC), 9-fluorenylmethoxycarbonyl (Fmoc) and benzyloxycarbonyl (cbz) and, GP 'is a hydrogen atom or a group protector selected from the group consisting of: t-butoxycarbonyl (BOC), 9-fluorenylmethoxycarbonyl (Fmoc), benzyloxycarbonyl (cbz), allyl, 4-methoxybenzyl, 2,4-dimethoxybenzyl and N-benzylamine. Even more preferred is the embodiment in which the group GP protector is t-butoxycarbonyl (BOC) and GP 'is a hydrogen atom In another preferred embodiment of the invention, GP and GP 'taken together form a phthalimido group.

In a also preferred embodiment of the invention, the compounds of formula (II), alternatively (II '), they are those in which R_ {1} and R2 are independently selected from the group consisting of: methyl, isobutyl, phenyl, methylphenyl, ethylphenyl, 2-naphthyl, t-butyldiphenylsilyloxypropyl and t-butyldimethylsilyloxypropyl. In one embodiment more preferred, the compounds of formula (II), alternatively (II '), are those in which R_ {1} is selected from isobutyl, t-butyldimethylsilyloxypropyl, t-butyldimethylsilyloxypropyl, phenyl, methylphenyl and ethylphenyl and, R2 is selected from methyl, phenyl and 2-naphthyl.

In formulas (II) and (II '), the lines wavy means any of the two possible configurations of the chiral carbon to which they are attached. In the context of this invention, the term "substantially pure enantiomer" means a compound with sufficient enantiomeric excess for its industrial scale preparation, which depends on each case concrete as the expert in the field will decide. In most of In cases, an enantiomeric excess greater than 95% is enough.

Dehydration can be carried out using a carbodiimide as a dehydrating agent in the presence of a Catalytic amount of anhydrous copper (II) chloride. Preferably carbodiimide is the p-toluenesulfonate of 1-cyclohexyl-3- (2-morpholinoethyl) -carbodiimide. Alternatively, dehydration is carried out by reaction. with an alkylsulfonyl chloride and an amine, except when R, is phenyl, substituted phenyl or naphthyl. In a preferred embodiment the alkylsulfonyl chloride is mesyl chloride and the amine is 4- (dimethylamino) pyridine. Dehydration reactions are carried out in a solvent suitable for reagents and materials used and suitable for the transformation to be produce When the dehydrating agent is a carbodiimide a example of suitable solvent is acetonitrile and the reaction is performed at a temperature between 20ºC and 70ºC. When he dehydrating agent is an alkylsulfonyl chloride, examples of Suitable organic solvents include chlorinated hydrocarbons such such as dichloromethane, ethers such as tetrahydrofuran, and aromatic hydrocarbons such as toluene. Generally, the reactions are carried out at a temperature between 0 ° C and 40 ° C.

The compound of formula (II), alternatively (II '), is prepared by reaction of the compound of formula (III), alternatively (III '), with an oxidizing agent. Preferably the oxidizing agent is m-chloroperbenzoic acid, which It is usually used in excess, and in an appropriate solvent, such as for example chlorinated hydrocarbons such as dichloromethane or ethers such as tetrahydrofuran. Generally, the reaction is carried out at a temperature between 0 ° C and temperature environment.

3

The compound of formula (III), alternatively (III '), can be prepared by treating the compound of formula (IV), alternatively (IV '), with a thiol of formula R 2 -SH in the presence of a base and in a solvent inert, having R2 the same meaning as defined previously. Usually the reaction is carried out with a Thiol equivalent. The base can be a tertiary amine such as triethylamine or an inorganic base such as a metal hydroxide alkali, preferably the alkali metal being sodium or potassium. In a preferred embodiment, the thiol is selected from the thiophenol and 2-naphthylthiol, and the base is triethylamine. Alternatively, the thiol group may also be conveniently introduced by treating a compound of formula (IV), alternatively (IV '), with an alkali metal salt of the thiol, by usually used in excess and in an appropriate solvent, for example lower alcohols having 1 to 4 carbon atoms and its mixtures with water. Preferably, the solvent is methanol, optionally mixed with water. The temperature is not a parameter Critically and generally, it is between room temperature and the reflux temperature of the solvent used. In a preferred embodiment the alkali metal salt is methantiolate sodium

4

The epoxide as a starting material, of formula (IV), alternatively (IV '), can be prepared according to a known procedure summarized in Scheme 1 (cf. eg P. Castejón et al., Tetrahedron letters 1995, vol. 36, pp. 3019-3022). Essentially, the 3-amino-1,2-diol of formula (V), alternatively (V '), is subjected to the Mitsunobu cyclization conditions comprising the reaction with triphenylphosphine and diethyl or diisopropyl azodicarboxylate to obtain, after chromatographic purification, the corresponding anti- (1-aminoalkyl) epoxy N -protected. On the other hand, the 3-amino-1,2-diol of formula (V), alternatively (V '), can be converted into the corresponding non- (1-aminoalkyl) N- protected epoxide, through a simple procedure three-step comprising: a) selective protection of the primary alcohol of the compound (V), alternatively (V '); b) mesylation of secondary alcohol; and c) deprotection / cyclization carried out by successive treatment of the obtained mesylate, with tetrabutylammonium fluoride and sodium methoxide.

The compound of formula (V), alternatively (V '), can be obtained, in a very enantioselective way, by a method that includes the catalytic asymmetric epoxidation of Sharpless of allylic alcohols that are easily accessible, followed by a regal and stereoselective opening of the ring of oxirane, with an equivalent of ammonia (azide ion or benzydrylamine) (cf. eg, M. Canas et al., Tetrahedron Lett . 1991, vol. 32, pp. 6931-6934; M. Pastó et al., Tetrahedron Assimmetry 1996, vol. 7, pp. 243-262; M. Alcón et al., Tetrahedron Assimmetry 1997, vol. 8, pp. 2967-2974; P. Castejón et al., Tetrahedron Lett . 1995, vol. 17, pp. 3019-3022).

Scheme one

General compound preparation process of formula (IV), alternatively (IV ')

5

As mentioned above, the compound of formula (I), alternatively (I '), prepared according to the process of the present invention, is useful as an intermediate for the preparation of peptidyl vinyl sulfones. Therefore, another aspect of the present invention is the use of a compound of formula (I), alternatively (I '), prepared according to the present invention, for the preparation of said peptidyl vinyl sulfones. The compound of formula (I), alternatively (I '), can be treated using known techniques that allow the amine protecting group to be removed and then the free amine group, can be coupled with a carboxyl terminal group of a natural amino acid or of a peptide for obtaining a peptidyl vinyl sulfone of formula (VI), alternatively (VI '), wherein GP, R1 and R2 are as defined in claim 1; R 3 represents a side chain radical or a terminal chain radical of a natural amino acid or a peptide; m is an integer equal to or greater than one and, when m is greater than one, R 3 can be the same or different (cfr. eg J. Kong et al. J. Med . Chem. 1998, vol. 41, pp. 2579-2587; HS Overkleeft. Et al., Tetrahedron Letters 2000, vol. 41, pp. 6005-6009).

6

Another aspect of the present invention is provide a new stereoisomeric compound selected from the two enantiomeric formulas (II), alternatively (II '), where:

R 1 is a radical selected from the group consisting of: (C 1 -C 6) -alkyl, (C 3 -C 6) -cycloalkyl, [(C 1 -C_ {6}) - alkyldi-
phenylsilyloxy] - (C 1 -C 6) -alkyl, [(C 1 -C 6)-trialkylsilyloxy] - (C 1 -C 6) -alkyl, (C_ { 1 -C 4) - alkoxy, GP-O- (CH 2) n -, naphthyl, phenyl, Ph- (CH 2) n -, R-COO- ( CH 2) n - with R = (C 1 -C 6) -alkyl or phenyl, and a radical derived from the aforementioned mentioned with benzene rings through a mono- or a di- substitution in its benzene rings, the substituents being a radical independently selected from the group consisting of: halogen, (C 1 -C 4) -alkyl, (C 1 -C 4) -alkoxy, trifluoromethyl , a protected amino group and a protected hydroxyl;

R2 is a radical selected from it group than R 1, further including phenylcarbonyl;

n is an integer selected from 1 to 10; and GP represents an amine protecting group; GP 'represents an atom of hydrogen or an amine protecting group equal to or different from GP; or alternatively, GP and GP 'taken together form a group phthalimido

7

Especially preferred are the compounds of formula (II), alternatively (II '), where the GP protecting group is select from the group consisting of carbamates, amides and sulfonamides and, GP 'is a hydrogen atom or a protecting group selected from the same group as GP, also including an allyl, a benzyl and a mono or di-substituted benzyl. Even more Preferred are the compounds of formula (II), alternatively (II '), where the GP protecting group is selected from t-butoxycarbonyl (BOC), 9-fluorenylmethoxycarbonyl (Fmoc) and benzyloxycarbonyl (cbz) and, GP 'is a hydrogen atom or a group protector equal to or different from GP, selected from the group formed by: t-butoxycarbonyl (BOC), 9-fluorenylmethoxycarbonyl (Fmoc), benzyloxycarbonyl (cbz), allyl, 4-methoxybenzyl, 2,4-dimethoxybenzyl and N-benzylamine and, those where the protective group GP and GP 'taken together They form a phthalimido group. The most preferred are those where the GP protecting group is t-butoxycarbonyl (BOC) and GP ' It is a hydrogen atom.

Also preferred compounds of formula (II), alternatively (II '), are those where: R_ {1} and R2_ are independently selected from the group consisting of: methyl, isobutyl, phenyl, methylphenyl, ethylphenyl, 2-naphthyl, t-butyldiphenylsilyloxypropyl and t-butyldimethylsilyloxypropyl. Even more preferred are those compounds of formula (II), alternatively (II '), where: R1 is selected from the group consisting of: isobutyl, t-butyldiphenylsilyloxypropyl, t-butyldimethylsilyloxypropyl, phenyl, methylphenyl and ethylphenyl and R2 is selected from the group consisting of methyl, phenyl and 2-naphthyl.

This invention also provides new stereoisomeric compounds selected from those of formula (I), alternatively (I '), where R_ {1} is selected among the group consisting of: Ph-, Ph-CH2 -, t-butyldiphenylsilyloxypropyl, t-butyldimethylsilyloxypropyl; R2 is phenyl; Y GP represents an amine protecting group; GP 'represents an atom of hydrogen or an amine protecting group equal to or different from GP; or alternatively GP and GP 'taken together form a group phthalimido Especially preferred are the compounds of formula (I), alternatively (I ') where the protective group is a t-butoxycarbonyl (BOC) and GP 'is an atom of hydrogen.

8

An advantage of the present invention lies in the fact that this stereoselective procedure of preparation of γ-amino vinyl sulfones does not depend on the availability of a suitable α-amino acid. Another advantage of the present invention lies in the fact that the Stereoselective procedure of preparation of γ-amino vinyl sulfones can provide with equal ease both enantiomers of a γ-amino vinyl sulfone. Also present invention provides a short stereoselective procedure and efficient preparation of γ-amino vinyl sulfones, with high yields and high optical purity.

For those skilled in the art, other objects, advantages and features of the invention will be partly detached of the description and in part of the practice of the invention. At throughout the description and claims the word "understand" and its variants are not intended to exclude other technical characteristics, additives, components or steps. The description in the summary of this application is incorporated here as reference. The following examples are provided by way of illustration, and are not intended to be limiting of the present invention.

Examples

The following non-limiting examples illustrate the invention for a certain stereoisomeric configuration. When another configuration of stereoisomers is required, the invention can be carried out in a similar manner starting from compounds of proper configuration, as would be obvious to People with experience in the technique.

Example 1 Preparation of ( S ) - [( S ) -1- ( tert -butoxycarbonylamino) -3-phenylpropyl] oxirane (IV, R1 = Ph (CH2) 2)

To a solution of (2 S , 3 S ) - N -Boc-3-amino-5-phenylpentan-1,2-diol (0.10 g, 0.34 mmol) and triphenylphosphine (95 mg, 0.36 mmol) in anhydrous chloroform ( 2 ml) a solution of diisopropyl azodicarboxylate (71 µL, 0.36 mmol) in 1 ml of anhydrous chloroform was added. The reaction mixture was heated at reflux for 20 h, at which time the analysis by TLC showed the disappearance of the starting product. The solvent was evaporated, the residue was purified by silica column chromatography with hexane-ethyl acetate mixtures as eluents and 86 mg (92% yield) of the title product was obtained as a colorless solid. Mp: 68-70 ° C. [α] D 23 = -8.5 ( c = 1.02, CHCl 3). IR (NaCl film, ν max, cm -1): 2979, 1696, 1522, 1427, 1366, 1248, 1171. MS (Cl-NH 3, m / e ): 295 ( M + 18, 45%), 278 (M + 1, 46%), 240 (M-37, 100%).

Example 2 Preparation of ( S ) - [( S ) -1- ( tert -butoxycarbonylamino) -4- ( tert -butyldimethylsilyloxy) butyl] oxirane (IV, R1 = TBDMSO (CH2) 3)

Similarly, the title product was obtained in 81% yield, after chromatographic purification, from N -Boc-3-amino-3 - ( tert- butyldimethylsilyloxy) propan-1,2-diol (0.29 g , 0.80 mmol), diisopropyl azodicarboxylate (0.17 ml, 0.86 rmol) and triphenylphosphine (0.22 g, 0.86 mmol) in reflux chloroform (4 ml, 7 h) in the form of a colorless oil. [α] D 23 = -5.15 ( c = 1.04, CHCl 3). IR (NaCl film, ν max, cm -1): 2930, 2859, 1702, 1522, 1254, 1173, 1100, 836. MS (FAB +, NBA, m / e ): 346 (M +1, 100%), 468 (M + 23, 61%).

Example 3 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -3-phenyl-1-phenylthio-2-propanol (III, R1 = Ph, R2 = Ph)

To a solution of ( S ) - [( S ) -1- ( tert -butoxycarbonylamino) -3-phenylmethyl] oxirane (0.10 g, 0.40 mmol) in anhydrous methanol (4 ml), triethylamine (57 µl was added sequentially , 0.40 mmol) and thiophenol (41 µL, 0.40 mmol). The resulting mixture was heated to reflux until the CCF analysis showed the disappearance of the starting product (1 h). The solvent was removed, the residue was purified by column chromatography (silica previously treated with triethylamine, 2.5% v / v) with hexane-ethyl acetate mixtures as eluents and 143 mg (100% yield) of the compound was obtained. title in the form of a colorless solid. P. f. 119-120 ° C. [α] D 23 = +6.4 ( c = 1.02, CHCl 3). IR (NaCl film, ν max, cm -1): 1684, 1497, 1457, 1368, 1167. MS (Cl-NH3, m / e ): 360 (M + 1, 22%), 359 (M, 100%), 321 (M-38, 56%), 304 (M-55, 43%).

Example 4 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -4-phenyl-1-phenylthio-2-butanol (III, R1 = PhCH2R2 = Ph)

\hbox{[ \alpha ] _{D}  ^{23} }

= -26.6 (c = 1.0, CHCl_{3}). IR (NaCl film, \nu _{max}, cm^{-1}): 3747, 3359, 1686, 1654, 1559, 1522, 1457, 1173, 741.Similarly, the title product was obtained in 100% yield (0.8 mmol). P. f. 148-149 ° C.

 \ hbox {[α] D 23 

= -26.6 ( c = 1.0, CHCl3). IR (NaCl film, ν max, cm -1): 3747, 3359, 1686, 1654, 1559, 1522, 1457, 1173, 741.

Example 5 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -5-phenyl-1-phenylthio-2-pentanol (III; R 1 = Ph (CH 2) 2 R_ { 2} = Ph)

Similarly, the title product was obtained in 78% yield, after chromatographic purification, from ( S ) - [( S ) -1- ( tert -butoxycarbonylamino) -3-phenylpropyl] oxirane (0.50 g , 1.8 mmol), thiophenol (184 µL, 1.8 mmol) and triethylamine (255 µL, 1.8 mmol) in reflux methanol (18 ml, 4 h). P. f. 118-119 ° C. [α] D 23 = -11.6 ( c = 0.7, CHCl 3). IR (NaCl film, ν max, cm -1): 3347, 1681, 1528, 1299, 1248, 1169, 1017. MS (Cl-NH3, m / e ): 388 ( M + 1, 100%), 349 (M-38, 55%), 332 (M-55, 34%).

Example 6 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -5-methyl-1-phenylthio-2-hexanol (III, R 1 = (CH 3) 2 CHCH 2 }, R2 = Ph)

Similarly, the title product was obtained in 84% yield, after chromatographic purification, from epoxy IV, R 1 = (CH 3) 2 CHCH 2 (0.30 g , 1.3 mmol), thiophenol (135 µl, 1.3 mmol) and triethylamine (185 µl, 1.3 mmol) in methanol at reflux (10 ml, 1 h). P. f. 83-85 ° C. [α] D 23 = -25.3 ( c = 1.02, CHCl 3). IR (NaCl film, ν max, cm -1): 1684, 1654, 1559, 1507, 1368, 1167, 737, 668. MS (Cl-NH 3, m / e ): 340 (M + 1, 6%), 339 (M, 32%), 284 (M-55, 100%).

Example 7 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -6- ( tert -butyldimethylsiloxy) -1-phenylthio-2-hexanol (III, R1 = TBDMSO (CH2)) 3} R2 = Ph)

Similarly, the title product was obtained in 89% yield, after chromatographic purification, from ( S ) - [( S ) -1- ( tert -butoxycarbonylamino) -4- ( tert -butyldimethylsilyloxy) butyl ] oxirane (0.17 g, 0.50 mmol), thiophenol (51 µL, 0.50 mmol) and triethylamine (71 µL, 0.51 mmol) in methane) at reflux (5 ml, 1.5 h) in the form of a colorless oil. [α] D 23 = -10.0 ( c = 1.1, CHCl 3). IR (NaCl film, ν max, cm -1): 2931, 1696, 1654, 1507, 1252, 1169, 1100, 836. MS (FAB +, NBA, m / e ): 456 (M +1, 100%), 478 (M + 23, 39%).

Example 8 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -5-phenyl-2-naphthylthio-2-pentanol (III, R1 = Ph (CH2) 2, R_ {2} = naphthyl)

To a solution of ( S ) - [( S ) -1- ( tert -butoxycarbonylamino) -3-phenylpropyl] oxirane (0.50 g, 1.80 mmol) in anhydrous methanol (18 ml), triethylamine (255 µl was added sequentially , 1.82 mmol) and 2-naphthylthiol (0.29 g, 1.80 mmol). The resulting mixture was heated at reflux for 4 h, at which time the analysis by TLC showed the disappearance of the starting epoxide. The solvent was removed, the residue was purified by column chromatography (silica previously treated with triethylamine, 2.5% v / v) with hexane-ethyl acetate mixtures as eluents and 143 mg (87% yield) of the compound was obtained. title in the form of a colorless solid. Mp 125-127 ° C. [α] D 23 = -23.0 ( c = 1.01, CHCl 3). IR (NaCl film ν max, cm -1): 3357, 1683, 1524, 1297, 1248, 1173, 1021. MS (Cl-NH3) m / e : 455 (M + 18, 69%), 438 (M + 1, 36%), 437 (M, 100%).

Example 9 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -3-phenyl-1-methylthio-2-propanol (III, R1 = Ph, R2 = CH3)

\hbox{[ \alpha ] _{D}  ^{23} }

= +29.2 (c = 1.05, CHCl_{3}). IR (NaCl film, \nu _{max}, cm^{-1}): 3377, 1684, 1654, 1522, 1457, 1246, 1171, 1015. MS (Cl-NH_{3}, m/e): 315 (M+18, 9%), 298 (M+1, 100%), 259 (M-38, 75%), 242 (M-55, 23%).A solution of ( S ) - [( S ) -1- ( tert -butoxycarbonylamino) -3-phenylmethyl] oxirane (0.10 g, 0.40 mmol) and sodium methantiolate (34 mg, 0.50 mmol) in methane was heated to reflux ) anhydrous (5 ml) until the analysis by CCF showed the disappearance of the starting epoxide (4 h). The solvent was removed, the residue was purified by column chromatography (silica previously treated with triethylamine, 2.5% v / v) with hexane-ethyl acetate mixtures as eluents and 100 mg (yield 84%) of the compound was obtained. title in the form of a colorless solid. P. f. 129-130 ° C.

 \ hbox {[α] D 23 

= +29.2 ( c = 1.05, CHCl3). IR (NaCl film, ν max, cm -1): 3377, 1684, 1654, 1522, 1457, 1246, 1171, 1015. MS (Cl-NH3, m / e ): 315 (M + 18, 9%), 298 (M + 1, 100%), 259 (M-38, 75%), 242 (M-55, 23%).

Example 10 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -4-phenyl-1-methylthio-2-butane) (III, R 1 = PhCH 2 R 2 = CH 3 })

Similarly, the title product was obtained in 92% yield, after chromatographic purification, from ( S ) - [( S ) -1- ( tert -butoxycarbonylamino) -3-phenylethyl] oxirane (0.20 g , 0.76 mmol) and sodium methantiolate (60 mg, 0.84 mmol) in methanol at reflux (10 ml, 0.5 h). P. f. 134.5-135.5 ° C. [α] D 23 = -7.0 ( c = 1.0, CHCl 3). IR (NaCl film, ν max, cm -1): 3357, 1685, 1527, 1316, 1250, 1171, 1015, 702 cm -1. MS (Cl-NH3, m / e ): 312 (M + 1, 76%), 273 (M-38, 100%), 256 (M-55, 99%).

Example 11 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -5-phenyl-1-methylthio-2-pentanol (III, R1 = Ph (CH2) 2R_ { 2} = CH 3)

Similarly, the title product was obtained in 78% yield, after chromatographic purification, from ( S ) - [( S ) -1- ( tert -butoxycarbonylamino) -3-phenylpropyl] oxirane (0.50 g , 1.8 mmol) and sodium methantiolate (150 mg, 2.2 mmol) in methanol at reflux (20 ml, 4 h). P. f. 108-109 ° C. [α] D 23 = -7.6 ( c = 1.02, CHCl 3). IR (NaCl film, ν max, cm -1): 3357, 1685, 1522, 1248, 1173, 1019, 699. MS (Cl-NH3, m / e ): 343 ( M + 18, 100%), 326 (M + 1, 15%), 325 (M, 83%), 287 (M-38, 32%).

Example 12 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -5-methyl-1-methylthio-2-hexanol (III, R 1 = (CH 3) 2 CHCH 2 }, R2 = CH3)

Similarly, the title product was obtained in 86% yield, after chromatographic purification, from the epoxide (IV, R 1 = (CH 3) 2 CHCH 2), (0.30 g, 1.31 mmol) and sodium methantiolate (101 mg, 1.44 mmol) in reflux methanol (20 ml, 1 h). P. f. 109-110 ° C. [α] D 23 = -24.4 ( c = 1.0, CHCl 3). IR (NaCl film, ν max, cm -1): 3359, 2952, 1679, 1530, 1329, 1254, 1171. MS (Cl-NH3, m / e ): 295 ( M + 18, 8%), 278 (M + 1, 100%), 239 (M-38, 23%), 223 (M-54, 58%).

Example 13 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -3-phenyl-1-phenylsulfonyl-2-propanol (II, R1 = Ph, R2 = Ph)

To a solution of the sulfide prepared in example 3 (0.107 g, 0.30 mmol) in anhydrous dichloromethane (6 ml), a solution of m- chloroperbenzoic acid (0.130 g, 0.75 mmol) in anhydrous dichloromethane was added dropwise (6 ml). The reaction mixture was stirred at room temperature (ta) until the analysis by TLC showed the disappearance of the starting product (3 h); It was cooled to 0 ° C and treated with a 10% sodium sulphite solution (4 ml). After 15 min of stirring, the aqueous phase was separated. The organic phase was washed with a saturated sodium bicarbonate solution (5 ml) and with a saturated sodium chloride solution (5 ml) and dried with anhydrous magnesium sulfate. The solvent was removed, the residue was purified by column chromatography (silica previously treated with triethylamine, 2.5% v / v) with hexane-ethyl acetate mixtures as eluents and 115 mg (100% yield) of the compound was obtained. title in the form of a colorless solid. P. f. 158-160 ° C. [α] D 23 = +3.2 ( c = 1.1, CHCl 3). IR (NaCl film, ν max, cm -1): 3504, 1702, 1497, 1366, 1308, 1153. MS (Cl-NH3, m / e ): 409 (M + 18, 100%), 354 (M-37, 74%), 335 (M-55, 82%).

Example 14 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -3-phenyl-1-methylsulfonyl-2-propanol (II, R 1 = Ph, R 2 = CH 3)

Similarly, the title product was obtained in 100% yield, after chromatographic purification, from the sulfide prepared in example 9 (55 mg, 0.3 mmol). IR (NaCl film, ν max, cm -1): 1719, 1685, 1507, 1366, 1283, 1121, 1071. MS (Cl-NH 3, m / e ): 347 ( M + 18, 9%), 330 (M + 1, 88%), 291 (M-38, 18%), 274 (M-55, 100%).

Example 15 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -4-phenyl-1-phenylsulfonyl-2-butanol (II, R 1 = PhCH 2, R 2 = Ph)

Similarly, the title product was obtained in 81% yield, after chromatographic purification, from the sulfide prepared in example 4 (0.20 g, 0.55 mmol). P. f. 154-155 ° C. [α] D 23 = +3.0 ( c = 1.04, CHCl 3). IR (NaCl film, ν max, cm -1): 3355, 1692, 1526, 1316, 1148, 1013, 739. MS (Cl-NH3, m / e ): 423 ( M + 18, 7%), 406 (M + 1, 5%), 405 (M, 19%), 366 (M-39, 100%), 349 (M-56, 41%).

Example 16 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -4-phenyl-1-methylsulfonyl-2-butanol (II, R., = PhCHz, R2 = CH3)

Similarly, the title product was obtained in 80% yield, after chromatographic purification, from the sulfide prepared in example 10 (0.20 g, 0.64 mmol). P. f. 155-156 ° C. [α] D 23 = -23.1 ( c = 0.9, CHCl 3). IR (NaCl film, ν max, cm -1): 3359, 1686, 1521, 1301, 1254, 1169, 1129, 1013. MS (Cl-NH 3) m / e : 344 (M + 1, 2%), 343 (M, 11%), 305 (M-38, 100%), 288 (M-55, 19%).

Example 17 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -5-phenyl-1-phenylsulfonyl-2-pentanol (II, R1, = Ph (CH2) 2, R2 = Ph)

Similarly, the title product was obtained in 100% yield, after chromatographic purification, from the sulfide prepared in example 5 (0.155 g, 0.40 mmol). P. f. 129-130 ° C. [α] D 23 = -13.5 ( c = 1.0, CHCl 3). IR (NaCl film, ν max, cm -1): 2362, 2341, 1717, 1507, 1289, 1144. MS (Cl-NH3, m / e ): 437 (M + 18, 16%), 420 (M + 1, 15%), 381 (M-38, 22%), 380 (M-39, 100%).

Example 18 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -5-phenyl-1-methylsulfonyl-2-pentanol (II, R1 = Ph (CH2) 2R_ { 2} = CH 3)

Similarly, the title product was obtained in 80% yield, after chromatographic purification, from the sulfide prepared in example 11 (0.20 g, 0.62 mmol). P. f. 125-127 ° C. [α] D 23 = -11.6 ( c = 1.0, CHCl 3). IR (NaCl film ν max, cm -1): 1685, 1522, 1457, 1299, 1129, 473. MS (Cl-NH3, m / e ): 374 (M + 18 , 100%).

Example 19 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -5-phenyl-1- (2-naphthylsulfonyl) -2-pentanol (II, R1 = Ph (CH2)) 2}, R2 = naphthyl)

Similarly, the title product was obtained in 87% yield, after chromatographic purification, from the sulfide prepared in Example 8 (0.30 g, 0.69 mmol). P. f. 158-159 ° C. [α] D 23 = -17.7 ( c = 1.03, CHCl 3). IR (NaCl film, ν max, cm -1): 1696, 1507, 1368, 1304, 1246, 1144, 1127, 1019, 749. MS (Cl-NH 3, m / e ): 487 (M + 18, 100%), 431 (M-38, 5%).

Example 20 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -5-methyl-1-phenylsulfonyl-2-hexanol (II, R 1 = (CH 3) 2 CHCH 2 }, R2 = Ph)

Similarly, the title product was obtained in 97% yield, after chromatographic purification, from the sulfide prepared in example 6 (0.20 g, 0.60 mmol). P. f. 106-107 ° C [α] D 23 = -16.2 ( c = 1.03, CHCl 3). IR (NaCl film, ν max, cm -1): 2960, 1962, 1521, 1449, 1368, 1304, 1144 .. MS (Cl-NH 3, m / e ): 372 (M + 1, 18%), 371 (M, 86%), 316 (M-55, 100%).

Example 21 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -5-methyl-1-methylsulfonyl-2-hexanol (II, R 1 = (CH 3) 2, CHCH_ { 2}, R2 = CH3)

Similarly, the title product was obtained in 86% yield, after chromatographic purification, from the sulfide prepared in Example 12 (0.10 g, 0.36 mrnol). P. f. 137-138 ° C. [α] D 23 = -22.8 ( c = 1.0, CHCl 3). IR (NaCl film, ν max, cm -1): 2960, 1686, 1522, 1393, 1368, 1295, 1167, 1133. MS (Cl-NH 3, m / e ): 327 (M + 18, 29%), 310 (M + 1, 23%), 271 (M-38, 100%), 254 (M-55, 15%).

Example 22 Preparation of (2 S , 3 S ) -3- ( tert -butoxycarbonylamino) -6- ( tert -butyldimethylsilyloxy) -1-phenylsulfonyl-2-hexanol (II, R1 = TBDMSO (CH2) _ 3}, R2 = Ph)

Similarly, the title product was obtained in 85% yield, after chromatographic purification, from the sulfide prepared in example 7 (80 mg, 0.18 mmol) as a colorless oil. [α] D 23 = -4.1 ( c = 1.7, CHCl 3). IR (NaCl film, ν max, cm -1): 2931, 1685, 1507, 1366, 1306, 1252, 1146, 1086, 836. MS (FAB +, NBA, m / e ): 488 (M + 1, 47%), 510 (M + 23, 100%).

Example 23 Preparation of (3 S , E ) -3- ( tert -butoxycarbonylamino) -4-phenyl-1-phenylsulfonyl-1-butene (I, R1 = PhCH2R2 = Ph)

To a cold solution (0 ° C) of the 2-hydroxy sulfone prepared in example 15 (85 mg, 0.21 mmol) and 4- ( N, N- dimethylamino) pyridine (105 mg, 0.86 mmol) in anhydrous dichloromethane (2 ml ), a solution of mesyl chloride (33 ml, 0.43 mmol) in anhydrous dichloromethane (1 ml) was added. The reaction mixture was stirred at room temperature for 30 min, at which time the analysis by TLC showed the disappearance of the starting product. The reaction mixture was diluted with dichloromethane (3 ml), and washed sequentially with a cold solution (0 ° C) of 10% HCl (10 ml) and with a saturated sodium bicarbonate solution (2x5 ml). The organic phase was dried with anhydrous magnesium sulfate and the solvent was removed under reduced pressure. The residue was purified by column chromatography (silica previously treated with triethylamine, 2.5% v / v) with hexane-ethyl acetate mixtures as eluents and 76 mg (94% yield) of the title compound was obtained as a colorless solid. P. f. 139.0-140.5 ° C. [α] D 23 = +3.2 ( c = 1.05, CHCl 3). IR (NaCl film, ν max, cm -1): 1702, 1507, 1447, 1368, 1308, 1148, 1086, 753. MS (Cl-NH3, m / e ): 405 (M + 18, 100%), 348 (M-39, 30%).

Example 24 Preparation of (3 S , E ) -3- ( tert -butoxycarbonylamino) -4-phenyl-1-methylsulfonyl-1-butene (I, R1 = PhCH2R2 = CH3)

Similarly, the title product was obtained in 100% yield, after chromatographic purification, from the sulfone prepared in example 16 (18 mg, 0.052 mmol). P. f. 145-146 ° C. [α] D 23 = +8.4 ( c = 0.83, CHCl 3). A 95% ee was determined by HPLC (Chiralpak column AS, 80: 20 hexane: isopropyl alcohol; t R ( R ) = 25.3 min, t R ( S ) = 29.2 min).

Example 25 Preparation of (3 S , E ) -3- ( tert -butoxycarbonylamino) -5-phenyl-1-phenylsulfonyl-1-pentene (I, R1 = Ph (CH2) 2, R_ { 2} = Ph)

Similarly, the title product was obtained in 100% yield, after chromatographic purification, from the sulfone prepared in example 17 (100 mg, 0.24 mmol). P. f. 78-80 ° C. [α] D 23 = -1.3 ( c = 0.9, CHCl 3). IR (NaCl film ν max, cm -1): 1702, 1517, 1368, 1308, 1250, 1148, 1086. MS (Cl-NH3, m / e ): 419 (M +18, 100%), 363 (M-38, 33%), 345 (M-56, 19%).

Example 26 Preparation of (3 S , E ) -3- ( tert -butoxycarbonylamino) -5-phenyl-1-methylsulfonyl-1-pentene (I, R 1 = Ph (CH 2) 2 R 2 } = CH 3)

Similarly, the title product was obtained in 100% yield, after chromatographic purification, from the sulfone prepared in Example 18 (100 mg, 0.28 mmol). P. f. 118-120 ° C. [α] D 23 = +5.6 ( c = 1.04, CHCl 3). IR (NaCl film, ν max, cm -1): 1700, 1521, 1310, 1248, 1167, 1135, 1048, 967, 668. MS (Cl-NH3, m / e ): 357 (M + 18, 100%), 301 (M- 38, 9%).

Example 27 Preparation of (3 S , E ) -3- ( tert -butoxycarbonylamino) -5-phenyl-1- (2-naphthylsulfonyl) -1-pentene (I, R1 = Ph (CH2) 2 }, R2 = naphthyl)

Similarly, the title product was obtained in 100% yield, after chromatographic purification, from the sulfone prepared in Example 19 (100 mg, 0.28 mmol). P. f. 123-126 ° C (decomp.). [α] D 23 = +0.6 ( c = 1.02, CHCl 3). IR (NaCl film, ν max, cm -1): 3855, 1702, 1654, 1559, 1507, 1457, 1148, 1127, 668. MS (Cl-NH 3, m / e ): 469 (M + 18, 100%).

Example 28 Preparation of (3 S , E ) -3- ( tert -butoxycarbonylamino) -5-methyl-1-phenylsulfonyl-1-hexene (I, R 1 = (CH 3) 2 CHCH 2 , R2 = Ph)

Similarly, the title product was obtained in 94% yield, after chromatographic purification, from the sulfone prepared in example 20 (100 mg, 0.28 mmol). P. f. 74-75 ° C. [α] D 23 = -6.0 ( c = 1.0, CHCl 3). IR (NaCl film, ν max, cm -1): 3363, 2959, 1702, 1517, 1368, 1308, 1148, 1086. MS (Cl-NH3, m / e ): 371 (M + 18, 100%), 315 (M-38, 33%).

Example 29 Preparation of (3 S , E ) -3- (tert-butoxycarbonylamino) -5-methyl-1-methylsulfonyl-1-hexene (I, R 1 = (CH 3) 2 CHCH 2 , R2 = CH3)

Similarly, the title product was obtained in 88% yield, after chromatographic purification, from the sulfone prepared in Example 21 (50 mg, 0.16 mmol). P. f. 69-70 ° C. [α] D 23 = -20.3 ( c = 1.0, CHCl 3). IR (NaCl film, ν max, cm -1): 3357, 2960, 1702, 1521, 1393, 1368, 1310, 1252, 1169, 1136. MS (Cl-NH3, m / e ): 309 (M + 18, 100%), 253 (M-38, 97%).

Example 30 Preparation of (3 S , E ) -3- ( tert -butoxycarbonylamino) -6- ( tert -butyldimethylsilyloxy) -1-phenylsulfonyl-1-hexene (I, R1 = TBDMSO (CH2) 3 } R2 = Ph)

Similarly, the title product was obtained in 100% yield, after chromatographic purification, from the sulfone prepared in example 22 (67 mg, 0.17 mmol) as a colorless oil.
[α] D 23 = - 3.0 ( c = 1.2, CHCl 3). IR (NaCl film ν max, cm -1): 2931, 1702, 1507, 1252, 1148, 1086, 1017, 836. MS (FAB +, NBA) m / e : 492 (M + 23 , 46%).

Example 31 Preparation of (3 S , E ) -3- ( tert -butoxycarbonylamino) -3-phenyl-1-phenylsulfonyl-1-propene (I, R1, = Ph, R2 = Ph)

To a solution of the 2-hydroxy sulfone prepared in example 13 (50 mg, 0.13 mmol) in anhydrous acetonitrile (2 ml), 1-cyclohexyl-3- (2-morpholinoethyl) -carbodiimide p-toluenesulfonate was added sequentially (110 mg, 0.26 mmol) and anhydrous cupric chloride (2 mg), and the resulting mixture was heated at 70 ° C for 1 h. The reaction mixture was allowed to cool to room temperature and filtered through celite and silica by washing with dichloromethane. The solvent was removed under reduced pressure and the title compound (48 mg, 100% yield) was obtained as a colorless solid. P. f. 88-89 ° C. [α] D 23 = +31.5 ( c = 1.04, CHCl 3). IR (NaCl film ν max, cm -1): 1700, 1507, 1320, 1148,1086, 753, 689. MS (Cl-NH3, m / e ): 391 (M +18, 99%), 374 (M + 1, 4%), 335 (M-38, 100%), 318 (M-55, 9%).

Example 32 Preparation of (3 S , E ) -3- ( tert -butoxycarbonylamino) -3-phenyl-1-methylsulfonyl-1-propene (I, R 1, = Ph, R 2 = CH 3)

Similarly, the title product was obtained in 96% yield from the 2-hydroxy sulfone prepared in example 14 (45 mg, 0.14 mmol). P. f. 128-130 ° C. [α] D 23 = +50.3 ( c = 0.30, CHCl 3). IR (NaCl film ν max, cm -1): 1702, 1654, 1559, 1507, 1457, 1312, 1165, 1135, 969, 700. MS (Cl-NH3) m / e : 329 (M + 18, 100%), 274 (M-37, 13%).

Claims (28)

1. A stereoselective procedure of preparation of a substantially pure enantiomer of the γ-amino vinyl sulfone of formula (I), alternatively (I '), which comprises a dehydration step of a β-hydroxy-γ-amino sulfone of formula (II), alternatively (II '): 9 where: in formulas (II) and (II '), the wavy line means any of the two possible configurations of the chiral carbon to which they are attached; R 1 is a radical to select from the group consisting of: (C 1 -C 6) -alkyl, (C 3 -C 6) -cycloalkyl, [(C 1 -C_ {6}) - alkyldi-
phenylsilyloxy] - (C 1 -C 6) -alkyl, [(C 1 -C 6)-trialkylsilyloxy] - (C 1 -C 6) -alkyl, (C_ { 1 -C 4) -alkoxy, GP-O- (CH 2) n -, naphthyl, phenyl, Ph- (CH 2) n -, R-COO- ( CH 2) n - with R = (C 1 -C 6) -alkyl or phenyl, and a radical derived from those mentioned above with benzene rings through a mono- or a di- substitution in its benzene rings, the substituents being a radical independently selected from the group consisting of: halogen, (C 1 -C 4) -alkyl, (C 1 -C 4) -alkoxy, trifluoromethyl , a protected amino group and a protected hydroxyl; R2 is a radical selected from it group than R 1, further including phenylcarbonyl; n is an integer selected from 1 to 10; Y GP represents an amine protecting group; GP 'represents a hydrogen atom or a group amine protector equal to or different from GP, or alternatively, GP and GP 'taken together they form a phthalimido group. 2. The stereoselective procedure of preparation according to claim 1, wherein the GP protecting group is selected from the group consisting of: carbamates, amides and sulfonamides and, GP 'is a hydrogen atom or a protecting group of amines selected from the same group as GP, also including a allyl, a benzyl and a mono benzyl or di-substituted. 3. The stereoselective procedure of preparation according to claim 2, wherein the GP protecting group is selected from the group consisting of: t-butoxycarbonyl (BOC), 9-fluorenylmethoxycarbonyl (Fmoc) and benzyloxycarbonyl (cbz) and, GP 'is a hydrogen atom or a group amine protector, same or different from GP, selected from the group consisting of: t-butoxycarbonyl (BOC), 9-fluorenylmethoxycarbonyl (Fmoc), benzyloxycarbonyl (cbz), allyl, 4-methoxybenzyl, 2,4-dimethoxybenzyl and N-benzylamine. 4. The stereoselective procedure of preparation according to claim 3, wherein the GP protecting group is t-butoxycarbonyl (BOC) and GP 'is an atom of hydrogen. 5. The stereoselective procedure of preparation according to claim 1, wherein the GF 'protecting group and GP 'taken together form a phthalimido group. 6. The stereoselective procedure of preparation according to claim 1, wherein R 1 and R 2 are independently selected from the group consisting of: methyl, isobutyl, phenyl, methylphenyl, ethylphenyl, 2-naphthyl, t-butyldiphenylsilyloxypropyl and t-butyldimethylsilyloxypropyl. 7. The stereoselective procedure of preparation according to claim 6, wherein R1 is selected among the group consisting of: isobutyl, t-butyldiphenylsilyloxypropyl, t-butyldimethylsilyloxypropyl, phenyl, methylphenyl and ethylphenyl and, R2 is selected from the group consisting of methyl, phenyl and 2-naphthyl. 8. The stereoselective procedure of preparation according to claim 1, wherein the step of dehydration is carried out by reaction with a carbodiimide in presence of a catalytic amount of copper (II) chloride anhydrous. 9. The stereoselective procedure of preparation according to claim 8, wherein carbodiimide is the p-toluenesulfonate of 1-cyclohexyl-3- (2-morpholinoethyl) -carbodiimide. 10. The stereoselective procedure of preparation according to claim 1, wherein the step of dehydration is carried out by reaction with a chloride of alkylsulfonyl and an amine, with the proviso that R1 is not phenyl, phenyl-substituted or naphthyl. 11. The stereoselective procedure of preparation according to claim 10, wherein the chloride of alkylsulfonyl is mesyl chloride. 12. The stereoselective preparation process according to claim 11, wherein the amine is 4- (dimethylami-
no) pyridine. 13. The stereoselective procedure of preparation according to claim 1, wherein the compound of formula (II), alternatively (II '), is prepared by reaction of compound of formula (III), alternatively (III '), with an agent oxidizer in an inert solvent. 10 14. The stereoselective preparation process according to claim 13, wherein the oxidizing agent is m- chloroperbenzoic acid. 15. The stereoselective procedure of preparation according to claim 13, wherein the compound of formula (III), alternatively (III '), is prepared by reaction of compound of formula (IV), alternatively (IV '), with a thiol of formula R2 -SH in the presence of a base, or with an alkali metal salt thereof, in an inert solvent, having R_ {2} has the same meaning as defined previously. eleven 16. The stereoselective procedure of preparation according to claim 15, wherein the thiol is selected between thiophenol and 2-naphthylthiol. 17. The stereoselective procedure of preparation according to claim 16, wherein the base is triethylamine 18. The stereoselective procedure of preparation according to claim 15, wherein the metal salt Alkaline is sodium methantiolate. 19. A preparation procedure comprising the step defined in claim 1, and the subsequent transformation of a compound of formula (I), alternatively (I '), in a peptidyl vinyl sulfone of formula (VI), alternatively (VI '), through a deprotection reaction of the amino group, followed by a coupling reaction of the group amino deprotected with a carboxyl terminal group, of a N-protected amino acid or peptide N-protected, where, GP, R_ {1} and R2 are like were defined in claim 1; R 3 represents a radical of a side chain or an amino acid terminal chain natural or of a peptide; m is an integer greater than or equal to one and, when m is greater than one, R_ {3} can be the same or different. 12 20. A selected stereoisomeric compound between the two enantiomeric formulas, (II), alternately (II '), where: R 1 is a radical selected from the group consisting of: (C 1 -C 6) -alkyl, (C 3 -C 6) -cycloalkyl, [(C 1 -C_ {6}) - alkyldi-
phenylsilyloxy] - (C 1 -C 6) -alkyl, [(C 1 -C 6)-trialkylsilyloxy] - (C 1 -C 6) -alkyl, (C_ { 1 -C 4) -alkoxy, GP-O- (CH 2) n -, naphthyl, phenyl, Ph- (CH 2) n -, R-COO- ( CH 2) n - with R = (C 1 -C 6) -alkyl or phenyl, and a radical derived from those mentioned above with benzene rings through a mono- or a di- substitution in its benzene rings, the substituents being a radical independently selected from the group consisting of: halogen, (C 1 -C 4) -alkyl, (C 1 -C 4) -alkoxy, trifluoromethyl , a protected amino group and a protected hydroxyl; R2 is a radical selected from it group than R 1, further including phenylcarbonyl; n is an integer selected from 1 to 10; Y GP represents an amine protecting group; GP 'represents a hydrogen atom or a group amine protector equal to or different from GP; or alternatively, GP and GP 'taken together they form a phthalimido group. 13 21. The stereoisomeric compound according to claim 20, wherein the GP protecting group is selected from the group consisting of: carbamates, amides and sulfonamides and, GP 'is a hydrogen atom or a selected amine protecting group from the same group as GP, also including an allyl, a benzyl and a mono or di-substituted benzyl. 22. The stereoisomeric compound according to the claim 21, wherein the GP protecting group is selected from the group consisting of: t-butoxycarbonyl (BOC), 9-fluorenylmethoxycarbonyl (Fmoc) and benzyloxycarbonyl (cbz) and, GP 'is a hydrogen atom or a group amine protector, same or different from GP, selected from the group consisting of: t-butoxycarbonyl (BOC), 9-fluorenylmethoxycarbonyl (Fmoc), benzyloxycarbonyl (cbz), allyl, 4-methoxybenzyl, 2,4-dimethoxybenzyl and N-benzylamine. 23. The stereoisomeric compound according to claim 22, wherein the GP protecting group is t-butoxycarbonyl (BOC) and GP 'is an atom of hydrogen. 24. The stereoisomeric compound according to claim 20, wherein the protective group GP and GP 'taken together they form a phthalimido group. 25. The steroisomeric compound according to the claim 20, wherein R1 and R2 are independently selected from the group consisting of: methyl, isobutyl, phenyl, methylphenyl, ethylphenyl, 2-naphthyl, t-butyldiphenylsilyloxypropyl and t-butyldimethylsilyloxypropyl. 26. The steroisomeric compound according to claim 25, wherein R1 is selected from the group formed by: isobutyl, t-butyldiphenylsilyloxypropyl, t-butyldimethylsilyloxypropyl, phenyl, methylphenyl and ethylphenyl and, R2 is selected from the group consisting of methyl, phenyl and 2-naphthyl. 27. A selected stereoisomeric compound among those of formula (I), alternatively (I '), where: R_ {1} is selected from the group consisting of: Ph-, Ph-CH2 -, t-butyldiphenylsilyloxypropyl, t-butyldimethylsilyloxypropyl; R2 is phenyl; Y GP represents a protective group of amines. GP 'represents a hydrogen or a protecting group of amine equal to or different from GP; or alternatively, GP and GP 'taken together they form a phthalimido group. 14 28. The stereoisomeric compound according to claim 27, wherein the protecting group is the t-butoxycarbonyl (BOC) and GP 'is an atom of hydrogen.