WO2007088559A1

WO2007088559A1 - Process for producing substituted sulphoxides

Info

Publication number: WO2007088559A1
Application number: PCT/IN2007/000035
Authority: WO
Inventors: Sushil Kumar Dubey; Gaurav Vig; Anand Singh; Sushil Tripathi; Soumendu Paul
Original assignee: Jubilant Organosys Limited
Priority date: 2006-02-01
Filing date: 2007-01-31
Publication date: 2007-08-09

Abstract

A process for preparing substituted sulphoxide using asymmetric oxidation of a pro-chiral sulphide employing a novel enantioselective agent along with oxidizing agents optionally in presence of an organic solvent, wherein said enantioselective agents is chiral transition metal complex or chiral dioxiranes. The chiral ligand used in this process is selected from dicyclohexylidene or diacetonide or substituted or unsubstituted benzylidene derivatives of sugars.

Description

PROCESS FOR PRODUCING SUBSTITUTED SULPHOXIDES

Field of the Invention This invention, in general, relates to a process for producing substituted sulphoxides. More particularly, the present invention provides a process for producing substituted sulphoxides either as a single enantiomer or in an enantiomerically enriched form employing a novel enantioselective agent.

Background of the Invention

Different substituted 2-(2-pyridinylmethyl sulphinyl)-lH-benzimidazoles such as omeprazole, lansoprazole, pantoprazole and rabeprazole are known as gastric acid secretion inhibitors. Omeprazole, chemically known as 5-methoxy-2-[[(4-methoxy-3,5- dimethyl-2-pyridinyl)methylsulphinyl-lH-benzimidazole) described in EP 5129, is useful proton pump inhibitor i.e. effective in inhibiting the gastric acid secretion .

These structurally related sulphoxide compounds have a stereogenic center at the sulphur atom and thus exist as enantiomers. The resolution of different substituted 2-(2- pyridinylmethyl sulphmyl)-lH-benzimidazole is disclosed in DE4035455 and WO94/27988. According to these processes, diastereomeric mixture is prepared from the racemate of the corresponding substituted 2-(2-pyridinylmethyl sulphinyl)-lH- benzimidazole, which is subsequently resolved and finally one of the separated diastereomer is converted to optically pure sulphoxide in a hydrolytic step. The resolution process mentioned above has several disadvantages, for example multiple resolution steps and waste of refined material in the form of unwanted stereoisomer.

In US 5,948,789 and Eur. J. Biochem. 166 (1987), 453, enatioselective synthesis of substituted sulphoxides are described. In this process, a pro-chiral sulphide is oxidized to the corresponding sulphoxide either as a single enantiomer or in an enantiomerically enriched form using oxidizing agent in the presence of a chiral titanium complex, wherein the chiral titanium complex is prepared by reacting the titanium isopropoxide or propoxide with chiral ligand. The chiral ligand is selected from (+)-diethyl L-tartrate or (-)-diethyl D-tartatrate. International Patent Publication No. WO2005054228 describes an enatioselective process for the preparation of substituted benzimidazole, wherein, the substituted pro- chiral sulphide, preferably halo or nitro substituted, is asymmetrically oxidized using an oxidizing agent in the presence of chiral titanium complex to the corresponding sulphoxide, either as a single enantiomer or in an enantiomerically enriched form. The chiral titanium complex is prepared from a chiral ligand and titanium compounds wherein the chiral ligand is selected from (-)-diethyl D-tartatrate and (+)-diethyl L- tartrate.

International Patent Publication No. WO2005080374 describes enatioselective synthesis of sulphoxide compound, either as a single enantiomer or in an enantiomerically enriched form, by oxidizing pro-chiral sulphide with an oxidizing agent in the presence of chiral titanium complex, wherein the chiral titanium complex is prepared by reacting titanium compound with chiral ligand. The chiral ligand is selected from chiral diol such as (+)-diethyl L-tartrate or (-)-diethyl D-tartrate.

These processes disclosed in the prior art suffer from one or more drawbacks including use of expensive chiral ligands like (+)-diethyl L-tartrate or (-)-diethyl D-tartatrate, restricted/ strict condition during the oxidation, formation of oxidation by-product which makes the process industrially uneconomical.

Therefore, there is a need for an industrially feasible process for the preparation of substituted sulphoxides, either as a single enantiomer or in an enantiomerically enriched form, which could overcome the limitations associated with the prior art processes viz. use of expensive reagents, formation of oxidation by-product and should be cost effective too. The present invention addresses these needs.

Summary of the Invention

It is, therefore, a principal object of the present invention to devise a novel process to produce substituted sulphoxide either as a single enantiomer or enantiomerically enriched form to improve upon limitations of the processes disclosed in the prior arts. These and other objects are attained in accordance with the present invention wherein there is provided several embodiments of process for producing substituted sulphoxide either as a single enantiomer or enantiomerically enriched form employing a novel enantioselective agent.

In accordance with one preferred embodiment of the present invention, there is provided a process for producing substituted sulphoxide either as a single enantiomer or enantiomerically enriched form, wherein said process comprises of oxidizing a pro- chiral sulphide asymmetrically employing a novel chiral-ligand transition metal complex along with oxidizing agent optionally in presence of an organic solvent.

In accordance with another preferred embodiment of the present invention, there is provided a process for producing substituted sulphoxide either as a single enantiomer or enantiomerically enriched form, wherein said process comprises of oxidizing a pro- chiral sulphide asymmetrically employing a chiral dioxirane along with oxidizing agent in presence of an organic solvent.

In accordance with one other preferred embodiment of the present invention, there is provided a process for producing substituted sulphoxide either as a single enantiomer or enantiomerically enriched form, wherein said chiral transition metal complex is prepared by reacting a chiral ligand and transition metals either in the presence of pro- chiral sulphide or before the addition of pro-chiral sulphide to the reaction vessel.

In accordance with yet another preferred embodiment of the present invention, there is provided a process for producing substituted sulphoxide either as a single enantiomer or enantiomerically enriched form, wherein said chiral ligand is selected from dicyclohexylidene or diacetonide or substituted or unsubstituted benzylidene derivatives of aldohexoses, aldopentoses, ketohexoses, oligosaccharides or disaccharides and wherein the transition metal used is preferably selected from vanadium, titanium, irconium, haffhium and the like

In accordance with yet another preferred embodiment of the present invention, there is provided a process for producing substituted sulphoxide either as a single enantiomer or enantiomerically enriched form, wherein said chiral dioxirane is prepared by oxidizing said chiral ligand. In accordance with yet another preferred embodiment of the present invention, there is provided a process for producing substituted sulphoxide either as a single enantiomer or enantiomerically enriched form, wherein said asymmetric oxidation is carried out optionally in presence of an organic or inorganic base.

Detail Description of the Invention

While this specification concludes with claims particularly pointing out and distinctly claiming that, which is regarded as the invention, it is anticipated that the invention can be more readily understood through reading the following detailed description of the invention and study of the included examples.

The disclosed embodiment of the present invention provides a cost effective and industrial feasible process for the production of substituted sulphoxides wherein said process comprises of oxidizing a pro-chiral sulphide asymmetrically employing a novel enantioselective agent along with oxidizing agent optionally in presence of an organic solvent, wherein said enantioselective agent is selected from chiral-ligand transition metal complex or chiral dioxirane.

The process according ' to the present invention for the production of substituted sulphoxides of Formula [A],

Formula [A]

wherein R₁, R₂, R₃ R₄ are same or different and selected from the group consisting of hydrogen, C_1-4 linear or branched alkyl, C_1-4 linear or branched alkoxy, aryl, aryloxy, or its pharmaceutically acceptable salts, comprises asymmetrically oxidizing a pro-chiral sulphide of the Formula [B]

Formula [B]

wherein the R₁, R₂, R₃, R_4, are as defined above, employing a novel chiral transition metal complex along with oxidizing agent optionally in presence of an organic solvent.

The oxidizing agent used herein for the asymmetric oxidation of said pro-chiral sulphide of the Formula [B] employing chiral transition metal complex is selected from alkyl hydroperoxide or aryl alkyl hydroperoxide, preferably tertiary butyl hydroperoxide or cumene hydroperoxide.

The novel chiral ligand used in the preparation of chiral transition metal complex is selected from dicyclohexylidene or diacetonide or substituted or unsubstituted benzylidene derivatives of aldohexoses, aldopentoses, ketohexoses, oligosaccharides or disaccharides or mixture thereof, preferably from l,2:5,6-£⁾z-O-cyclohexylidene-α-£>- glucofuranose, 1 ,2:4,5-D/-O-cyclohexylidene-/>fructopyranose, 1 ,2:5,6-Di-O- isopropylidene-α-D-glucofuranose, l,2:5,6-Dz-O-isopropylidene-2>mannitol, 1,2-O- cyclohexylidene-α-D-glucofuranose, 3-0-benzyl-l,2-0-cyclohexylidene-α-D- glucofuranose, 3 -O-benzyl- 1 ,2 : 5,6-£⁾/-O-cyclohexylidene- α-D-glucofuranose, 1 ,2-O- cyclohexylidene-α-D-xylofuranose, methyl 4,6-O-benzylidene-o/J>-glucopyranoside, methyl 4,6-O-benzylidene-2,3-/J>/-6>-toluene-/?-sulphonyl-α-/J>-glucopyranoside, methyl α-/J>-altropyranoside, methyl 2,3 -anhydro-4,6-O-benzylidene- α-D-allopyranoside, methyl 4,6-<9-benzylidene-α-Z)-altropyranoside or methyl 4,6-O-benzylidene-2,3-di-O- methyl-α-Z⁾-glucopyranoside. The transition metal used in the preparation of chiral transition metal complex is selected from vanadium, titanium, zirconium, hafnium or like.

The organic solvent used herein is preferably selected from toluene, ethyl acetate, methyl ethyl ketone, methyl isobutyl ketone, methylene chloride or any combination thereof. Said organic solvent may be employed alone or with water.

The base used herein according to the process is either an organic or inorganic base. The preferred organic base includes trimethylamine, triethylamine, tributylamine, diisopropylethylamine, pyridine morpholine, 4-dimethylammo pyridine or mixture thereof. The preferred inorganic base includes alkali metal carbonate, alkali metal bicarbonate or alkali metal hydroxide and mixture thereof.

The said process according to the present invention is carried out at a temperature in the range of 20-60⁰C, preferably between 25-55⁰C for a period of about 3-6 hours, preferably 4-5 hours under inert atmosphere.

In a further embodiment of the present invention, there is provided a novel process for the preparation of substituted sulphoxides of Formula [A] either as a single enantiomer or in an enantiomerically enriched form,

Formula [A]

wherein R₁, R₂, R₃ R₄ are same or different and selected from the group consisting of hydrogen, C_1-4 linear or branched alkyl, C_1-4 linear or branched alkoxy, aryl, aryloxy, or its pharmaceutically acceptable salts, by asymmetrically oxidizing a pro-chiral sulphide of the Formula [B] employing a chiral dioxirane along with oxidizing agent in presence of a solvent.

Formula [B]

wherein the R₁, R₂, R₃, R₄₁ are as defined above.

The oxidizing agent used herein for oxidizing said pro-chiral sulphide of the Formula

[B] employing a chiral dioxirane according to the process is preferably selected from oxone, peroxo acids such as rø-chloroperbenzoic acid, peracetic acid, peroxomonosulphuric acid, peroxonitric acid, peroxocarbonic acid peroxodisulfuric acid, peroxides such as hydrogen peroxide and the like. The most preferred oxidizing agents include oxone.

The chiral dioxirane compound used herein according to the process for the asymmetric oxidation is prepared by oxidation of chiral ligand by a known oxidation reaction disclosed in literature.

The chiral ligand used herein to prepare chiral dioxirane employed in oxidation of pro- chiral sulphide of the Formula [B] is selected from dicyclohexylidene or diacetonide or substituted or unsubstituted benzylidene derivatives of aldohexoses, aldopentoses, ketohexoses, oligosaccharides and disaccharides and mixture thereof, preferably from l,2:5,6-Z)/-O-cyclohexylidene-α-D-glucofuranose, l,2:4,5-Z)z-O-cyclohexylidene-Z)- fructopyranose, l,2:5,6-D/-O-isopropylidene-α-/>glucofuranose, 1,2:5, 6-Di-O- isopropylidene-D-mannitol, 1 ,2-Ocyclohexylidene- α-/>glucofuranose, 3-O-benzyl- 1 ,2-O-cyclohexylidene-α-Z⁾-glucofuranose, 1 ,2-Ο-cyclohexylidene-α-Z)-xylofuranose, methyl 4,6-O-benzylidene-ar-D-glucopyranoside, methyl «r-Z)-altropyranoside, methyl 2,3-anhydro-4,6-O-benzylidene-α-/J>-allopyranoside, methyl 4,6-O-benzylidene-α-Z)- altropyranoside and the like. The suitable organic solvent is used herein for oxidizing said pro-chiral sulphide of the Formula [B] is preferably selected from nitriles such as acetonitrile, propionitrile, butyronitrile, chlorinated solvent such as dichloromethane, chloroform, aromatic hydrocarbon such as toluene, xylene, cyclohexane and mixture thereof.

The base used herein according to the present invention is selected from organic or inorganic source. The preferred organic base includes trimethylamine, triethylamine, tributylamine, diisopropylethylamine, pyridine morpholine, 4-dimethylamino pyridine or mixture thereof. The preferred inorganic base includes alkali metal carbonate, alkali metal bicarbonate or alkali metal hydroxide and mixture thereof.

The asymmetric oxidation according to the process of the present invention is carried out at a temperature in the range of -20 to 25⁰C, preferably between -15 to 2O⁰C for a period of about 2-6 hours, preferably between 3-4 hours under inert atmosphere.

The pro-chiral sulphide of the Formula [B] used herein as a precursor in the process according to the present invention is prepared by any method known in the prior art.

The resulting sulphoxides of Formula [A] prepared according to any embodiment of the present invention may be converted into optically active alkali and/or alkaline earth metal salt of substituted sulphoxides by treating the optically active substituted sulphoxides compound of Formula [A], obtained by asymmetric oxidation of prochiral sulfide compound of Formula [B], with an alkali and/or alkaline earth metal source. The alkali or alkaline earth metal source may be selected from Na⁺, Li⁺, Mg⁺², Ca⁺² and Ba⁺² salts such as bicarbonates, carbonates, hydrides, hydroxides, halides, sulphates, and oxides, preferably sodium hydroxide, potassium hydroxide, barium hydroxide, lithium hydroxide, magnesium hydroxide, calcium halide, magnesium halide and barium halide=or the like.

The process according to the present invention, wherein said process can produce the (- ) and (+) enantiomers of substituted sulphoxides in a noticeably enantio-selective manner. The term "in a noticeably enantioselective manner" used herein means that the desired enantiomer is obtained in a selective manner or in predominant quantities compared to the other enantiomer.

The examples that follow are not intended to limit the scope of the invention as defined hereinabove or as claimed below.

Example 1

Preparation of 5-methoxy-2- IT (4-methoxy-3 ,5-dimethyl-2-p widinyl)methyl] sulfmyl] -IH-benzimidazole sodium salt To a suspension of vanadium oxytripropoxide (7.4 g) in toluene (200 ml), 1,2:4,5- Z)/-O-cyclohexylidene-/>fructopyranose (27.9 g) was added and the mixture was stirred for 10-15 minutes at room temperature under nitrogen atmosphere. 5- Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methyl]thio]-/H^'benzimidazole (10 g) was added to the resulting mixture and the temperature was raised up to 50- 55°C. Water(l ml) was added to the said mixture and stirred for one hour. The reaction mass was cooled to 25-3O⁰C and added AζiV-diisopropylethylamine (1.4 g) followed by addition of cumene hydroperoxide (5.2 g) dropwise over a period of an hour. The reaction mass was further stirred for 45 minutes at said temperature. Triethylamine (20 ml) was added to the resulting mass and extracted with water. The organic layer was separated and the aqueous layer was further extracted from methyl isobutyl ketone at pH 7.5 to 8.0. Aqueous sodium hydroxide (50%) was added to the organic layer under stirring. Initially the solution was cooled at 10- 15⁰C, for half an hour under stirring and then at 20-25°C for 2 hrs. The resulting solid was filtered off, washed with solvent and dried under vacuum at 40-45⁰C. Yield = 5.8 g

Enantiomeric excess = 75%.

Example 2

Preparation of 5-methoxy-2-|^'[(^'4-methoxy-3,5-dimethyl-2-pyridinvDmethyll sulfinyl] -lH-benzimidazole

To a suspension of vanadium oxytripropoxide (1.2 g) in ethyl acetate (200 ml), l,2:4,5-Dz-O-cyclohexylidene-/>fructopyranose (1.0 g) was added and the mixture was stirred for 10-15 minutes at room temperature under nitrogen atmosphere. 5- Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methyl]thio]-7/-^rbenzimidazole (10 g) was added to the resulting mixture and the temperature was raised up to 50- 55⁰C. Water (0.02 ml) was added to the said mixture and stirred for one hour. The reaction mass was cooled between 25-3O⁰C and added ΛζiV-diisopropylethylamine (0.7 g) followed by addition of cumene hydroperoxide (2.6 g) dropwise over a period of one hour. The reaction mass was further stirred for 18 hours at said temperature. Triethylamine (20 ml) was added to the resulting mixture and was extracted with water. The organic layer was separated and the aqueous layer was further extracted from dichloromethane at pH 8.0 to 8.5. The organic layer was combined and distilled under vacuum to obtain the product as oily mass. Yield = 4.0 g

Enantiomeric excess = 67%.

Example 3

Preparation of 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinvDmethvπ sulfinyl] -l//-benzimidazole

5-Methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methyl]thio]-7J/ benzimidazole (10 g) was taken in acetonitrile (150 ml) and to this add l,2:4,5-/J⁾/-O-cyclohexylidene- β-D-erythro hexo-2,3-diulopyranose (10.2 g) was added under an nitrogen atmosphere. The reaction mixture was stirred at 15-2O⁰C for 10-15 minutes. Ethylenediaminetetracetic acid solution (10 ml) was added at the same temperature and the reaction mixture was cooled to -15 to -1O⁰C. Oxone (22.8 g) and sodium bicarbonate (2.1 g) was added to the reaction mixture over a period of one hour. After the addition, the resulting mixture was stirred for additional two hours. To the resulting reaction mixture, water (100 ml) and dichloromethane (200 ml) was added and stirred for few minutes. The organic layer was separated off, distilled under reduced pressure to obtain the oily residue. Yield = 3.5 g

Enantiomeric excess = 77%.

While this invention has been described in detail with reference to certain preferred embodiments, it should be appreciated that the present invention is not limited to those precise embodiments rather, in view of the present disclosure, which describes the current best mode for practicing the invention, many modifications and variations, would present themselves to those skilled in the art without departing from the scope and spirit of this invention.

Claims

We claim:

1. A process for preparing substituted sulphoxide of Formula [A] either as a single enantiomer or enantiomerically enriched form,

Formula [A] the process comprising: asymmetrically oxidizing apro-chiral sulphide of Formula [B],

Formula [B] employing a transition metal complex of chiral ligand along with oxidizing agent, wherein said chiral ligand is selected from dicyclohexylidene or diacetonide or substituted or unsubstituted benzylidene derivatives of sugar, wherein, R₁, R₂, R₃ R₄ are same or different and selected from the group consisting of hydrogen, Ci_-4 linear or branched alkyl, Ci_-4 linear or branched alkoxy, aryl, aryloxy, or its pharmaceutically acceptable salts.

2. The process according to claim 1 , wherein the sugar is preferably selected from aldohexoses, aldopentoses, ketohexoses, oligosaccharides or disaccharides.

3. The process according to claim 1, wherein the chiral ligand is preferably selected from l,2:5,6-Z)z-O-cyclohexylidene-α-Z)-gIucofuranose, 1 ,2:4,5-/J>z-0-cyclohexylidene-£⁾-fructopyranose, 1 ,2:5,6-.Dz^'-O-isopropylidene- <2-£>-glucofuranose, l,2:5,6-Z)/-<>isopropylidene-i}-rnarinitol, 1,2-0- cyclohexylidene-α-/>glucofuranose, 3-C?-benzyl- 1 ,2-O-cyclohexylidene-α-/> glucofuranose, 3-O-benzyl- 1 ,2 : 5,6-/J>z^'-O-cyclohexylidene- α-D-glucofuranose, 1 ,2-O-cyclohexylidene- α-/>xylofuranose, methyl 4,6-O-benzylidene- a-D- glucopyranoside, methyl 4,6-O-benzylidene-2,3 -Λ-O-toluene-p-sulphonyl- a- />glucopyranoside, methyl α-D-altropyranoside, methyl 2,3-anhydro-4,6-O- benzylidene-α-£>-allopyranoside, methyl 4,6-O-benzylidene- a-D- altropyranoside or methyl 4,6-O-benzylidene-2,3-di-O-methyl-α-/> glucopyranoside.

4. The process according to claim I₃ wherein the oxidizing agent is preferably selected from alkyl hydroperoxide or aryl alkyl hydroperoxide.

5. The process according to claim 1, wherein the chiral transition metal complex is prepared by reacting transition metal with a chiral ligand.

6. The process according to claim 1, wherein the transition metal is selected from vanadium, titanium, zirconium or haffnium.

7. The process according to claim 1, wherein the asymmetric oxidation is carried out optionally in presence of a base.

8. The process according to claim 7, wherein the base is either organic or inorganic.

9. A process for preparing substituted sulphoxide of Formula [A] either as a single enantiomer or enantiomerically enriched form,

Formula [A] the process comprising: asymmetrically oxidizing a pro-chiral sulphide of Formula [B]

Formula [B] employing a chiral dioxirane along with oxidizing agent in presence of organic solvent, wherein, R₁, R₂, R₃ R₄ are same or different and selected from the group consisting of hydrogen, C_1-4 linear or branched alkyl, C_1-4 linear or branched alkoxy, aryl, aryloxy, or its pharmaceutically acceptable salts.

10. The process according to claim 9, wherein said oxidizing agent is selected from peroxo acids, peroxides or oxone.

11. The process according to claim 10, wherein said oxidizing agent is preferably oxone.

12. The process according to claim 9, wherein said chiral dioxirane is prepared by oxidation of chiral ligand.

13. The process according to claim 12, wherein the chiral ligand is selected from dicyclohexylidene or diacetonide or substituted or unsubstituted benzylidene derivatives of aldohexoses, aldopentoses, ketohexoses, oligosaccharides or disaccharides.

14. The process according to claim 13, wherein the chiral ligand is preferably selected from l,2:5,6-D/-O-cyclohexylidene-α-_JD-glucofuranose, l,2:4,5-D/-Ο-cyclohexylidene-/J>-fructopyranose, l,2:5,6-Dz-O-isopropylidene- α-D-glucofuranose, l,2:5,6-Z⁾z-O-isopropylidene-Z>-mannitol, 1,2-O- cyclohexylidene-α-/>glucofuranose, 3-O-benzyl-l,2-O-cyclohexylidene-αr-.C>- glucofuranose, l,2-O-cyclohexylidene-α-Z>-xylofuranose, methyl 4,6-0- benzylidene-α-Z)-glucopyranoside, methyl osO-altropyranoside, methyl 2,3- anhydro-4,6-O-benzylidene-α-jD-allopyranoside or methyl 4₅6-O-benzylidene- α-Z)-altropyranoside .

15. The process according to claim 9, wherein the asymmetric oxidation is carried out optionally in presence of base.

16. The process according to claim 15, wherein the base is either organic or inorganic.

17. The process according to claim 9, wherein the organic solvent is selected from nitriles, aliphatic hydrocarbon, aromatic hydrocarbon or any combination thereof.

18. A process for preparing substituted sulphoxide of Formula

[A],

Formula [B] employing a novel enantioselective agent along with oxidizing agents, wherein said enantioselective agents is chiral transition metal complex or chiral dioxiranes and wherein said chiral ligand is selected from dicyclohexylidene or diacetonide or substituted or unsubstituted benzylidene derivatives of sugar, wherein, Rj, R₂, R₃ R₄ are same or different and selected from the group consisting of hydrogen, C_1-4 linear or branched alkyl, C_1-4 linear or branched alkoxy, aryl, aryloxy, or its pharmaceutically acceptable salts.

19. The process according to claim 18, wherein the sugar is preferably selected from aldohexoses, aldopentoses, ketohexoses, oligosaccharides or disaccharides.

20. The process according to claim 18, wherein the chiral ligand is preferably selected from l,2:5,6-Z⁾?-O-cyclohexylidene-α-£>-glucofuranose,

1 ,2:4,5-Z⁾/-O-cyclohexylidene-/>fructopyranose, 1 ,2:5,6-£⁾/-O-isopropylidene- α-Z⁾-glucofuranose, l,2:5,6-D/-O-isopropylidene-/>mannitol, 1,2-0- cycIohexylidene-α-D-glucofuranose, 3-O-benzyl-l,2-O-cyclohexylidene-α-D- glucofuranose, 3-O-benzyl-l,2:5,6-£⁾/-O-cyclohexylidene-«-D-glucofuranose, l,2-O-cyclohexylidene-α-Z⁾-xylofuranose, methyl 4,6-O-benzylidene-α-2)- glucopyranoside, methyl 4,6-O-benzylidene-2,3 -Dz-O-toluene-_jO-sulphonyl- a- Z⁾-glucopyranoside, methyl α-Z⁾-altropyranoside, methyl 2,3-anhydro-4,6-O- benzylidene-α-D-allopyranoside, methyl 4,6-O-benzylidene-Qr~/J>- altropyranoside or methyl 4,6-O-berizylidene-2,3-di-O-methyl-or-/J>- glucopyranoside.

21. The process according to claim 18, wherein the oxidizing agent is preferably selected from alkyl hydroperoxide, aryl alkyl hydroperoxide, peroxo acids, peroxides or oxone.

22. The process according to claim 21, wherein the transition metal is selected from vanadium, titanium, zirconium or hafnium.

23. The process according to claim 18, wherein the asymmetric oxidation is carried out optionally in presence of a base.

24. The process according to claim 23, wherein the base is either organic or inorganic.

25. The process according to claim 18, wherein said oxidation of pro-chiral sulphide using chiral dioxirane is carried out in presence of an organic solvent.

26. The process according to claim 25, wherein the organic solvent is selected from nitriles, aromatic hydrocarbon, chlorinated hydrocarbons or any combination thereof.