Method of preparation of 6-azido-2,4-diacetamido-2,4,6-trideoxy-D-mannose

Abstract

Disclosed is a method of preparation of 6-azido-2,4-diacetamido-2,4,6-trideoxy-D-mannose. This method includes the chemical reaction of compound of formula X: ##STR00001##
Wherein: R.sup.1 can be a C.sub.1 to C.sub.6 alkyl including methyl, ethyl, isopropyl; aryl including phenyl; each of these groups being substituted or not; and R.sup.2 can be a C.sub.1 to C.sub.6 alkyl including methyl, ethyl, isopropyl, tert-butyl, isobutyl; each of these groups being substituted or not; with a deprotecting reagent including a Lewis or Brnsted acid in a polar aprotic solvent, thereby obtaining a free C-1 OH group. The method can also start with the preparation from commercially available D-galactose pentaacetate, D-galactose tetraacetate or tetraacetyl D-galactosyl trichloroacetimidate. The step of deprotecting the anomeric position avoids the use of cerium and allows the easy purification of 6-azido-2,4-diacetamido-2,4,6-trideoxy-D-mannose.

Claims

1. A method of making 6-azido-2,4-diacetamido-2,4,6-trideoxy-D-mannose: ##STR00045## comprising reacting a compound of formula X: ##STR00046## wherein R.sup.1 is C.sub.1 to C.sub.6 alkyl or aryl, each of these groups being substituted or unsubstituted, and R.sup.2 is substituted or unsubstituted C.sub.1 to C.sub.6 alkyl; with a deprotecting reagent comprising a Lewis or Brnsted acid in a polar aprotic solvent, thereby obtaining a free C-1 OH group.

2. The method according to claim 1, wherein the compound of formula X is 1-trimethylsilylethanyl 6-azido-2,4-diacetamido-2,4,6-trideoxy--D-mannopyranoside: ##STR00047##

3. The method according to claim 1, wherein the compound of formula X is made by reacting a compound of formula IX: ##STR00048## wherein R.sup.1 is C.sub.1 to C.sub.6 alkyl or aryl, each of these groups being substituted or unsubstituted; R.sup.2 is substituted or unsubstituted C.sub.1 to C.sub.6 alkyl; and R.sup.4 is C.sub.1 to C.sub.6 alkyl, perfluoroalkyl or aryl, each of these groups being substituted or unsubstituted; with an azide formation reagent comprising an organic or inorganic azide salt in a non-polar solvent or in a polar aprotic solvent, thereby obtaining a 6-azido group.

4. The method according to claim 3, wherein the compound of formula IX is 1-trimethylsilylethanyl 2,4-diacetamido-2,4-dideoxy-6-O-mesyl--D-mannopyranoside: ##STR00049##

5. The method according to claim 3, wherein the compound of formula IX is made by reacting a compound of formula VIII: ##STR00050## wherein R.sup.1 is C.sub.1 to C.sub.6 alkyl or aryl, each of these groups being substituted or unsubstituted, and R.sup.2 is substituted or unsubstituted C.sub.1 to C.sub.6 alkyl; with a sulfonyl chloride or sulfonic anhydride in the presence of a base, with or without an organic solvent.

6. The method according to claim 5, wherein the compound of formula VIII is 1-trimethylsilylethanyl 2,4-diacetamido-2,4-dideoxy--D-mannopyranoside: ##STR00051##

7. The method according to claim 5, wherein the compound of formula VIII is made by reacting a compound of formula VII: ##STR00052## wherein R.sup.1 is C.sub.1 to C.sub.6 alkyl or aryl, each of these groups being substituted or unsubstituted, and R.sup.2 is substituted or unsubstituted C.sub.1 to C.sub.6 alkyl; in a protic solvent, with a reagent for the reduction of azido groups, then reacting the intermediate product obtained with an acylating reagent.

8. The method according to claim 7, wherein the compound of formula VII is 1-trimethylsilylethanyl 2,4-diazido-2,4-dideoxy--D-mannopyranoside: ##STR00053##

9. The method according to claim 7, wherein the compound of formula VII is made by reacting a compound of formula VI: ##STR00054## wherein R.sup.1 and R.sup.3 are C.sub.1 to C.sub.6 alkyl or aryl, each of these groups being substituted or unsubstituted, and R.sup.2 is substituted or unsubstituted C.sub.1 to C.sub.6 alkyl; in a protic solvent by using a reagent for deprotection of ester groups.

10. The method according to claim 9, wherein the reagent for deprotection of ester groups is sodium methanolate or potassium carbonate.

11. The method according to claim 9, wherein the compound of formula VI is made by reacting a compound of formula V: ##STR00055## wherein R.sup.1 and R.sup.3 are C.sub.1 to C.sub.6 alkyl or aryl, each of these groups being substituted or unsubstituted, and R.sup.2 is substituted or unsubstituted C.sub.1 to C.sub.6 alkyl; with an azido providing reagent, after adding to the organic solution, sulfonyl chloride or sulfonic anhydride in the presence of a base in a polar aprotic solvent.

12. The method according to claim 11, wherein the compound of formula V is made by reacting a compound of formula IV: ##STR00056## wherein R.sup.1 is C.sub.1 to C.sub.6 alkyl or aryl, each of these groups being substituted or unsubstituted, and R.sup.2 is substituted or unsubstituted C.sub.1 to C.sub.6 alkyl; with 2-aminoethyl diphenylborinate or bis(tributyltin)oxide and an acyl chloride in a polar aprotic solvent in the presence of a base.

13. The method according to claim 12, wherein the compound of formula IV is made by reacting a compound of formula III: ##STR00057## wherein R.sup.1 is C.sub.1 to C.sub.6 alkyl or aryl, each of these groups being substituted or unsubstituted, and R.sup.2 is substituted or unsubstituted C.sub.1 to C.sub.6 alkyl; in a protic solvent, in the presence of a reagent for the deprotection of ester groups.

14. The method according to claim 13, wherein the reagent for deprotection of ester groups is sodium methanolate or potassium carbonate.

15. The method according to claim 13, wherein the compound of formula III is made by reacting O-(2,3,4,6-tetra-O-acetyl--D-galactopyranosyl)trichloroacetimidate: ##STR00058## with a primary alcohol bearing a silyl group in the presence of a Lewis acid in a polar aprotic solvent.

16. The method according to claim 15, wherein the 0-(2,3,4,6-tetra-O-acetyl--D-alactopyranosyl) trichloroacetimidate is made by reacting 2,3,4,6-tetra-O-acetyl-D-galactopyranose: ##STR00059## with an imidate introducing reagent, in the presence of a base in a polar aprotic solvent.

17. A method of making 6-azido-2,4-diacetamido-2,4,6-trideoxy-d-mannose: ##STR00060## from commercially available d-galactose pentaacetate or D-galactose tetraacetate or tetraacetyl D-galactosyl trichloroacetimidate, according to the following reaction steps: ##STR00061## wherein R.sup.1 and R.sup.3 are C.sub.1 to C.sub.6 alkyl or aryl, each of these groups being substituted or unsubstituted; R.sup.2 is substituted or unsubstituted C.sub.1 to C.sub.6 alkyl; and R.sup.4 is C.sub.1 to C.sub.6 alkyl, perfluoroalkyl or aryl, each of these groups being substituted or unsubstituted.

18. A compound selected from the group consisting of: ##STR00062## wherein R.sup.1 is C.sub.1 to C.sub.6 alkyl or aryl, each of these groups being substituted or unsubstituted, and R.sup.2 is substituted or unsubstituted C.sub.1 to C.sub.6 alkyl; and ##STR00063## wherein R.sup.1 is C.sub.1 to C.sub.6 alkyl or aryl, each of these groups being substituted or unsubstituted; R.sup.2 is substituted or unsubstituted C.sub.1 to C.sub.6 alkyl; and R.sup.4 is C.sub.1 to C.sub.6 alkyl, perfluoroalkyl or aryl, each of these groups being substituted or unsubstituted.

19. A compound of formula VIII: ##STR00064## wherein R.sup.1 is C.sub.1 to C.sub.6 alkyl or aryl, each of these groups being substituted or unsubstituted, and R.sup.2 is substituted or unsubstituted C.sub.1 to C.sub.6 alkyl.

20. A compound selected from the group consisting of: ##STR00065## wherein R.sup.1 and R.sup.3 are C.sub.1 to C.sub.6 alkyl or aryl, each of these groups being substituted or unsubstituted, and R.sup.2 is substituted or unsubstituted C.sub.1 to C.sub.6 alkyl; and ##STR00066## wherein R.sup.1 and R.sup.3 are C.sub.1 to C.sub.6 alkyl or aryl, each of these groups being substituted or unsubstituted, and R.sup.2 is substituted or unsubstituted C.sub.1 to C.sub.6 alkyl.

Description

DETAILED DESCRIPTION OF THE BEST EMBODIMENT

(1) According to the invention, and in reference to Scheme 1 here-below, the target compound, 6-azido-2,4-diacetamido-2,4,6-trideoxy-D-mannose 11, was prepared in 13 steps from commercially available -D-galactose pentaacetate with an overall yield of 8 mol % and with a high purity of more than 95% by NMR analysis involving simple purification steps.

(2) According to specific embodiments the selective deprotection of the hydroxyl group at the anomeric position of -D-galactose pentaacetate with ethylenediamine in the presence of glacial acetic acid in dichloromethane gave compound 1 in a good 90% yield [1]. Activation of this hydroxyl group with trichloroacetonitrile in the presence of 1,8-diazabicyclo(5.4.0)undec-7-ene in dichloromethane gave trichloroacetimidate 2 with 72% yield [2]. This glycosyl donor 2 was confirmed by .sup.1H NMR to be the thermodynamically favored alpha anomer. Glycosylation of trimethylsilylethanol with compound 2 in the presence of trimethylsilyl trifluoromethanesulfonate in dry dichloromethane at 35 C. gave compound 3 in a good 76% yield [3]. Deacetylation using potassium carbonate [4] and selective benzoylation using the method developed by Lee and Taylor led to compound 5 (70% yield over 2 steps) [5]. Conversion of compound 5 into the bis-triflate derivative, and its subsequent reaction with tetra-n-butylammonium azide in toluene resulted into the bis-azido compound 6 (83% yield over 2 steps) [6], the manno configuration of which was confirmed by .sup.1H NMR spectroscopy (J.sub.1,2=1.1 Hz; J.sub.2,3=3.6 Hz; J.sub.3,4=10.2 Hz; J.sub.4,5=10.0 Hz). Debenzoylation of (6) in the presence of potassium carbonate and reduction of the azido groups with palladium hydroxide on charcoal in an hydrogen atmosphere was followed by N-acetylation to give compound 8 in a good yield (66% over 3 steps) [6]. The azido derivative 10 was obtained with a lower yield (36% over 2 steps) by selective mesylation in pyridine, with subsequent nucleophilic substitution using sodium azide in N,N-dimethylformamide [7]. The final product 11 was obtained in a good yield (84%) from compound 10 by deprotection of the anomeric position using trifluoroacetic acid in dichloromethane [8].

(3) Purification of product 11 is performed easily over inverse phase C18 silica. The purity of the final product is more than 95% by NMR analysis, and the overall yield for the synthesis of the product 11 is 8 mol %.

EXAMPLES OF SYNTHESIS OF THE INVENTION

(4) Materials and Methods:

(5) Thin layer chromatography was performed over Merck 60 F254 with detection by UV, and/or by charring with sulphuric acid or KMnO.sub.4 or phosphomolybdic acid solutions. Silica gel 60 40-63 m was used for flash column chromatography.

(6) NMR spectra were taken on Bruker Avance 300 or 500 MHz spectrometers, using the residual protonated solvent as internal standard. Chemical shifts are given in parts per million (ppm) and coupling constants are reported as Hertz (Hz). Splitting patterns are designated as singlet (s), doublet (d), triplet (t), doublet of doublet (dd), doublet of doublet of doublet (ddd). Splitting patterns that could not be interpreted or easily visualized are designated as multiplet (m).

(7) Mass spectra were taken on a Waters LCT Premier XE (ToF), with electrospray ionization in the positive (ESI.sup.+) mode of detection.

(8) IR-FT spectra were recorded on a Perkin Elmer Spectrum 100 spectrometer. Characteristic absorptions are reported in cm.sup.1.

(9) Specific optical rotations were measured at 20 C. with an Anton Paar MCP 300 polarimeter in a 10-cm cell at 20 C. and 589 nm.

(10) All chemical reagents were of analytical grade, obtained from commercial sources, and used without further purifications.

Invention Example 1

Synthesis of 6-azido-2,4-diacetamido-2,4,6-trideoxy-D-mannose (11) (Man2NAc4NAc6N.SUB.3.)

(11) ##STR00033##

(12) To a solution of compound 10 (77.0 mg, 0.20 mmol, 1.0 eq.) in CH.sub.2Cl.sub.2 (4.0 mL, 0.05 M) was added trifluoroacetic acid (1.5 mL, 2.3 g, 20.0 mmol, 100.0 eq.) at room temperature under an argon atmosphere. The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was diluted with toluene and ethyl acetate, then solvent were evaporated until dryness. Two others co-evaporations with toluene and ethyl acetate gave the crude solid. The residue was purified with C18 cartridge with H.sub.2O elution. Lyophilisation gave compound 11 (47.9 mg, 84%) as a white powder. Purity of more than 95% by NMR analysis.

(13) Rf (CH.sub.2Cl.sub.2/CH.sub.3OH 88:12): 0.23.

(14) IR (cm.sup.1): 3302, 2988, 2107, 1646, 1552, 1376, 1075.

(15) HMRS (ESI.sup.+): [M+H].sup.+ (C.sub.10H.sub.18N.sub.5O.sub.5.sup.+) Calc. m/z: 288.1302, found: 288.1297.

(16) Compound 11:

(17) .sup.1H-NMR (exchange with D.sub.2O) (500 MHz, CD.sub.3OD) : 5.09 (d, 1H, J.sub.1,2 1.6 Hz, H-1); 4.25 (dd, 1H, J.sub.2,3 4.6, J.sub.1,2 1.6 Hz, H-2); 4.06 (dd, 1H, J.sub.3,4 10.1, J.sub.2,3 4.6 Hz, H-3); 3.96 (ddd, 1H, J.sub.4,5 10.4, J.sub.5,6a 7.0, J.sub.5,6b 2.1 Hz, H-5); 3.93 (dd, 1H, J.sub.4,5 10.4, J.sub.3,4 10.1 Hz, H-4); 3.40 (dd, 1H, J.sub.6a,6b 13.3, J.sub.5,6a 7.0 Hz, H-6a); 3.27 (dd, 1H, J.sub.6a,6b 13.3, J.sub.5,6b 2.1 Hz, H-6b); 2.04 (s, 3H, COCH.sub.3); 1.98 (s, 3H, COCH.sub.3).

(18) .sup.13C-NMR (125 MHz, CD.sub.3OD) : 174.5, 174.3 (2 CO); 94.6 (C-1); 71.9 (C-5); 68.0 (C-3); 54.9 (C-2); 53.5 (C-6); 51.3 (C-4); 22.9 (COCH.sub.3); 22.7 (COCH.sub.3).

(19) Compound 11:

(20) .sup.1H-NMR (exchange with D.sub.2O) (500 MHz, CD.sub.3OD) : 4.84 (d, 1H, J.sub.1,2 1.6 Hz, H-1); 4.44 (dd, 1H, J.sub.2,3 4.1, J.sub.1,2 1.6 Hz, H-2); 3.79 (dd, 1H, J.sub.4,5 10.6, J.sub.3,4 9.8 Hz, H-4); 3.73 (dd, 1H, J.sub.3,4 10.6, J.sub.3,2 4.1 Hz, H-3); 3.48 (dd, 1H, J.sub.6a,6b 12.8, J.sub.6a,5 8.0 Hz, H-6a); 3.41 (ddd, 1H, J.sub.4,5 9.8, J.sub.5,6a 8.0, J.sub.5,6b 2.0 Hz, H-5); 3.28 (dd, 1H, J.sub.6a,6b 12.8, J.sub.6b,5 2.0 Hz, H-6b); 2.08 (s, 3H, COCH.sub.3); 1.98 (s, 3H, COCH.sub.3).

(21) .sup.13C-NMR (125 MHz, CD.sub.3OD) : 174.5, 174.3 (2 CO); 95.1 (C-1); 76.7 (C-5); 72.0 (C-3); 55.5 (C-2); 53.4 (C-6); 51.3 (C-4); 23.0 (COCH.sub.3); 22.7 (COCH.sub.3).

Invention Example 2

Synthesis of 1-trimethylsilylethanyl 6-azido-2,4-diacetamido-2,4,6-trideoxy--D-mannopyranoside (10)

(22) ##STR00034##

(23) The compound 9 (154.9 mg, 0.35 mmol, 1.0 eq.) and sodium azide (91.4 mg, 1.40 mmol, 4.0 eq.) were dissolved in dry dimethylformamide (7.0 mL, 0.05 M). The reaction mixture was stirred for 15 h at 80 C. Then the reaction mixture was cooled to room temperature and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography over silica gel (CH.sub.2Cl.sub.2/CH.sub.3OH 100:0 to 90:10) to give compound 10 (77.4 mg, 57%) as colourless oil. Purity of more than 95% by NMR analysis.

(24) Rf (CH.sub.2Cl.sub.2/CH.sub.3OH 9:1): 0.26.

(25) IR (cm.sup.1): 3278, 2097, 1657, 1551, 1068.

(26) .sup.1H-NMR (500 MHz, CDCl.sub.3) : 6.26 (br d, 1H, J.sub.4,NH 5.8 Hz, NH-(4)); 6.08 (d, 1H, J.sub.2,NH 5.2 Hz, NH-(2)); 5.54-5.36 (br s, 1H, OH-(3)); 4.66 (d, 1H, J.sub.1,2 1.5 Hz, H-1); 4.31 (ddd, 1H, J.sub.2,NH 5.2, J.sub.2,3 2.6, J.sub.1,2 1.5 Hz, H-2); 4.00 (ddd, 1H, J.sub.1a,2 9.9, J.sub.1a,1b 9.2, J.sub.1a,2 7.0 Hz, H-1a); 3.80-3.71 (m, 2H, H-3, H-4); 3.62 (ddd, 1H, J.sub.1b,2 9.8, J.sub.1a,1b 9.2, J.sub.1b,2 6.7 Hz, H-1b); 3.47 (dd, 1H, J.sub.6a,6b 13.0, J.sub.5,6a 8.3 Hz, H-6a); 3.42 (ddd, 1H, J.sub.4,5 9.1, J.sub.5,6a 8.3, J.sub.5,6b 1.3 Hz, H-5); 3.19 (dd, 1H, J.sub.6a,6b 13.0, J.sub.5,6b 1.3 Hz, H-6b); 2.08 (s, 3H, COCH.sub.3 (2)); 1.94 (s, 3H, COCH.sub.3 (4)); 0.96 (ddd, 1H, J.sub.2a,2b 13.8, J.sub.2a,1a 9.9, J.sub.2a,1b 6.7 Hz, H-2a); 0.92 (ddd, 1H, J.sub.2a,2b 13.8, J.sub.2b,1b 9.8, J.sub.2b,1a 7.0 Hz, H-2b); 0.00 (s, 9H, Si(CH.sub.3).sub.3).

(27) .sup.13C-NMR (125 MHz, CDCl.sub.3) : 174.6 (CO (2)); 172.0 (CO (4)); 98.2 (C-1); 77.2 (C-5); 72.5 (C-3); 67.5 (C-1); 55.7 (C-2); 52.3 (C-6); 50.8 (C-4); 23.5 (COCH.sub.3); 23.4 (COCH.sub.3); 18.1 (C-2); 1.1 (Si(CH.sub.3).sub.3).

(28) HMRS (ESI.sup.+): [2M+Na].sup.+ (C.sub.30H.sub.58N.sub.10O.sub.10Si.sub.2Na.sup.+) Calc. 797.3768, found 797.3795.

(29) [].sub.D=282.0 (c 1.0, CHCl.sub.3).

Invention Example 3

Synthesis of 1-trimethylsilylethanyl 2,4-diacetamido-2,4-dideoxy-6-O-mesyl--D-mannopyranoside (9)

(30) ##STR00035##

(31) To a solution of compound 8 (59.8 mg, 0.16 mmol, 1.0 eq.) in dry pyridine (1.5 mL, 0.10 M) at 10 C. was added mesyl chloride (19.1 L, 28.3 mg, 0.25 mmol, 1.5 eq.). The reaction mixture was stirred at 10 C. for 1 hour, then mesyl chloride (19.1 L, 28.3 mg, 0.25 mmol, 1.5 eq.) was added and the reaction mixture was stirred at 10 C. for 30 min, until complete conversion. The reaction mixture was then quenched with CH.sub.3OH and solvent evaporated under vacuum. The crude residue was purified by flash column chromatography over silica gel (CH.sub.2Cl.sub.2/CH.sub.3OH 100:0 to 90:10) to give compound 9 (44.2 mg, 63%) as white powder. Purity of more than 95% by NMR analysis.

(32) Rf (CH.sub.2Cl.sub.2/CH.sub.3OH 9:1): 0.38.

(33) .sup.1H-NMR (500 MHz, CDCl.sub.3) : 6.67 (d, 1H, J.sub.4,NH 7.8 Hz, NH-(4)); 6.33 (d, 1H, J.sub.2,NH 6.3 Hz, NH-(2)); 5.44-5.20 (br s, 1H, OH-(3)); 4.63 (d, 1H, J.sub.1,2 1.6 Hz, H-1); 4.36 (dd, 1H, J.sub.6a,6b 11.6, J.sub.5,6a 2.3 Hz, H-6a); 4.34 (ddd, 1H, J.sub.2,NH 6.3, J.sub.2,3 3.1, J.sub.1,2 1.6 Hz, H-2); 4.30 (dd, 1H, J.sub.6a,6b 11.6, J.sub.5,6b 6.1 Hz, H-6b); 3.94 (ddd, 1H, J.sub.1a,2 9.9, J.sub.1a,1b 8.9, J.sub.1a,2 7.2 Hz, H-1a); 3.85 (dd, 1H, J.sub.3,4 10.4, J.sub.2,3 3.1 Hz, H-3); 3.78 (ddd, 1H, J.sub.4,5 10.1, J.sub.3,4 10.4, J.sub.4,NH 7.8 Hz, H-4); 3.61 (ddd, 1H, J.sub.1b,2 9.6, J.sub.1a,1b 8.9, J.sub.1b,2 7.3 Hz, H-1b); 3.58 (ddd, 1H, J.sub.4,5 10.1, J.sub.5,6b 6.1, J.sub.5,6a 2.3 Hz, H-5); 3.03 (s, 3H, SCH.sub.3); 2.05 (s, 3H, COCH.sub.3); 1.95 (s, 3H, COCH.sub.3); 0.97-0.86 (m, 2H, 2H-2); 0.01 (s, 9H, Si(CH.sub.3).sub.3).

(34) .sup.13C-NMR (125 MHz, CDCl.sub.3) : 174.3, 172.3 (2 CO); 98.2 (C-1); 74.4 (C-5); 72.0 (C-3); 69.8 (C-6); 67.5 (C-1); 55.0 (C-2); 49.6 (C-4); 38.0 (SCH.sub.3); 23.5 (COCH.sub.3-(4)); 23.4 (COCH.sub.3-(2)); 18.1 (C-2); 1.1 (Si(CH.sub.3).sub.3).

(35) HMRS (ESI.sup.+): [2M+H].sup.+ (C.sub.32H.sub.65N.sub.4O.sub.16Si.sub.2S.sub.2.sup.+) Calc. 881.3370, found 881.3410.

Invention Example 4

Synthesis of 1-trimethylsilylethanyl 2,4-diacetamido-2,4-dideoxy--D-mannopyranoside (8)

(36) ##STR00036##

(37) A solution of compound 7 (237.8 mg, 0.72 mmol, 1.0 eq.) in CH.sub.3OH (7.2 mL, 0.10 M) was hydrogenated with 20% Pd(OH).sub.2/C (101.2 mg, 0.14 mmol, 0.20 eq.) at 40 C. for 3 hours under an hydrogen atmosphere. The catalyst was filtered off through Celite plug and the filtrate was concentrated to dryness. The crude residue was dissolved in CH.sub.3OH (7.2 mL, 0.10 M), acetic anhydride (0.27 mL, 293.8 mg, 2.88 mmol, 4.0 eq.) was added and the mixture was stirred for 1 hour at room temperature. The reaction mixture was concentrated until dryness. The residue was purified by flash column chromatography over silica gel (CH.sub.2Cl.sub.2/CH.sub.3OH, 100:0 to 90:10) to give compound 8 (181.3 mg, 69%) as a white powder. Purity of more than 95% by NMR analysis.

(38) Rf (CH.sub.2Cl.sub.2/CH.sub.3OH 9:1): 0.34.

(39) IR (cm.sup.1): 3676, 2988, 2902, 1407, 1382, 1250, 1230, 1066, 1028.

(40) .sup.1H-NMR (exchange with D.sub.2O) (500 MHz, CD.sub.3OD) : 4.58 (d, 1H, J.sub.1,2 1.4 Hz, H-1); 4.45 (dd, 1H, J.sub.2,3 3.8, J.sub.1,2 1.4 Hz, H-2); 3.99 (ddd, 1H, J.sub.1a,2a 9.5, J.sub.1a,1b 8.4, J.sub.1a,2b 7.3 Hz, H-1a); 3.79 (dd, 1H, J.sub.4,5 10.4, J.sub.3,4 10.1 Hz, H-4); 3.76 (dd, 1H, J.sub.3,4 10.1, J.sub.2,3 3.8 Hz, H-3); 3.68 (dd, 1H, J.sub.6a,6b 12.5, J.sub.5,6a 2.3 Hz, H-6a); 3.64 (dd, 1H, J.sub.6a,6b 12.5, J.sub.5,6b 3.9 Hz, H-6b); 3.63 (ddd, 1H, J.sub.1b,2b 9.3, J.sub.1a,1b 8.4, J.sub.1b,2a 6.9 Hz, H-1b); 3.24 (ddd, 1H, J.sub.4,5 10.1, J.sub.5,6b 3.9, J.sub.5,6a 2.3 Hz, H-5); 2.03 (s, 3H, COCH.sub.3); 1.99 (s, 3H, COCH.sub.3); 0.93 (ddd, 1H, J.sub.2a,2b 15.0, J.sub.2a,1a 9.5, J.sub.2a,1b 6.9 Hz, H-2a); 0.90 (ddd, 1H, J.sub.2a,2b 15.0, J.sub.2b,1b 9.3, J.sub.2b,1a 7.3 Hz, H-2b); 0.02 (s, 9H, Si(CH.sub.3).sub.3).

(41) .sup.13C-NMR (125 MHz, CD.sub.3OD) : 174.9, 174.8 (2 CO); 100.6 (C-1); 77.6 (C-5); 72.2 (C-3); 67.9 (C-1); 62.6 (C-6); 54.8 (C-2); 50.1 (C-4); 22.9 (COCH.sub.3); 22.8 (COCH.sub.3); 18.9 (C-2); 1.1 (Si(CH.sub.3).sub.3).

(42) HRMS (ESI.sup.+): [M+H].sup.+ (C.sub.15H.sub.31N.sub.2O.sub.6Si.sup.+) Calc. 363.1946, found 363.1959.

(43) [].sub.D=45.2 (c 1.0, CH.sub.3OH).

Invention Example 5

Synthesis of 1-trimethylsilylethanyl 2,4-diazido-2,4-dideoxy--D-mannopyranoside (7), Known from WO 2015/063173

(44) ##STR00037##

(45) To a solution of compound 6 (1.58 g, 2.94 mmol, 1.0 eq.) in CH.sub.3OH (30.0 mL, 0.10 M), was added K.sub.2CO.sub.3 (0.06 g, 0.44 mmol, 0.15 eq.) under an argon atmosphere. The reaction mixture was stirred at room temperature for 16 hours. Dowex H.sup.+ resin was added to the reaction mixture until neutral pH. The suspension was filtered off, washed with CH.sub.3OH, then the filtrate was concentrated. The residue was purified by flash column chromatography over silica gel (Heptane/Ethyl Acetate, 100:0 to 60:40) to give compound 7 (0.93 g, 96%) as a colourless oil. Purity of more than 95% by NMR analysis.

(46) Rf (Cyclohexane/Ethyl Acetate 6:4): 0.59.

(47) IR (cm.sup.1): 2112 (N.sub.3), 1250, 1073, 1028, 861, 838.

(48) .sup.1H-NMR (exchange with D.sub.2O) (500 MHz, CD.sub.3OD) : 4.65 (d, 1H, J.sub.1,2 0.9 Hz, H-1); 4.02 (ddd, 1H, J.sub.1a,2a 10.2, J.sub.1a,1b 9.7, J.sub.1a,2b 6.1 Hz, H-1a); 3.84 (dd, 1H, J.sub.2,3 3.7, J.sub.1,2 0.9 Hz, H-2); 3.80 (dd, 1H, J.sub.6a,6b 12.2, J.sub.5,6a 2.1 Hz, H-6a); 3.77 (dd, 1H, J.sub.3,4 9.8, J.sub.2,3 3.7 Hz, H-3); 3.69 (dd, 1H, J.sub.6a,6b 12.2, J.sub.5,6b 5.0 Hz, H-6b); 3.64 (ddd, 1H, J.sub.1b,2b 10.0, J.sub.1a,1b 9.7, J.sub.1b,2a 6.4 Hz, H-1b); 3.50 (dd, 1H, J.sub.4,5 10.2, J.sub.3,4 9.8 Hz, H-4); 3.11 (ddd, 1H, J.sub.4,5 10.2, J.sub.5,6b 5.0, J.sub.5,6a 2.1 Hz, H-5); 1.00 (ddd, 1H, J.sub.2a,2b 13.9, J.sub.2a,1a 10.2, J.sub.2a,1b 6.4 Hz, H-2a); 0.95 (ddd, 1H, J.sub.2a,2b 13.9, J.sub.2b,1b 10.0, J.sub.2b,1a 6.1 Hz, H-2b); 0.04 (s, 9H, Si(CH.sub.3).sub.3).

(49) .sup.13C-NMR (125 MHz, CD.sub.3OD) : 100.8 (C-1); 76.9 (C-5); 73.8 (C-3); 68.2 (C-1); 66.8 (C-2); 62.7 (C-6); 60.9 (C-4); 19.1 (C-2); 1.2 (Si(CH.sub.3).sub.3).

(50) HRMS (ESI.sup.+): [2M+H].sup.+ (C.sub.22H.sub.45N.sub.12O.sub.8Si.sub.2.sup.+) Calc. 661.3016, found 661.3021.

(51) [].sub.D=72.8 (c 1.0, CH.sub.3OH).

Invention Example 6

Synthesis of 1-trimethylsilylethanyl 2,4-diazido-2,4-dideoxy-3,6-di-O-benzoyl--D-mannopyranoside (6)

(52) ##STR00038##

(53) Trifluoromethanesulfonic anhydride (1.45 mL, 2.44 g, 8.6 mmol, 3.0 eq.) was added dropwise at 0 C. to a solution of compound 5 (1.41 g, 2.88 mmol, 1.0 eq.) and dry pyridine (1.40 mL, 1.37 g, 17.3 mmol, 6.0 eq.) in CH.sub.2Cl.sub.2 (20.0 mL, 0.15 M). The reaction mixture was stirred at 0 C. for 1 h30, diluted with CH.sub.2Cl.sub.2, and washed successively with H.sub.2O, a solution of 1N aq. HCl, a saturated solution of NaCl and then concentrated under vacuum. The crude bis-triflate obtained was dissolved in toluene (20.0 mL, 0.15 M) and tetra-n-butylammonium azide (4.92 g, 17.3 mmol, 6.0 eq.) was added. After stirring 1 h30 at 70 C. and 1 h30 at 100 C., the mixture was cooled, diluted with toluene, washed twice with water, a saturated solution of NaCl, and concentrated under vaccum. The residue was purified by flash column chromatography over silica gel (Petroleum Ether/Ethyl Acetate 100:0 to 80:20) to give compound 6 (1.28 g, 83%) as a colourless oil. Purity of more than 95% by NMR analysis.

(54) Rf (Cyclohexane/Ethyl Acetate 6:4): 0.82.

(55) IR (cm.sup.1): 2112 (N.sub.3), 1724, 1268, 1094, 710.

(56) .sup.1H-NMR (500 MHz, CDCl.sub.3) : 8.11 (dd, 2H, .sup.3J 8.3, .sup.4J 1.1 Hz, 2H-2a); 8.08 (dd, 2H, .sup.3J 8.3, .sup.4J 1.1 Hz, 2H-2b); 7.61 (tt, 1H, .sup.3J 7.4, .sup.4J 1.1 Hz, H-4a); 7.57 (tt, 1H, .sup.3J 7.4, .sup.4J 1.1 Hz, H-4b); 7.48 (dd, 2H, .sup.3J 8.3, .sup.3J 7.4 Hz, 2H-3a); 7.45 (dd, 2H, .sup.3J 8.3, .sup.3J 7.4 Hz, 2H-3b); 5.13 (dd, 1H, J.sub.3,4 10.2, J.sub.2,3 3.6 Hz, H-3); 4.73 (d, 1H, J.sub.1,2 1.1 Hz, H-1); 4.70 (dd, 1H, J.sub.6a,6b 12.0, J.sub.5,6a 2.4 Hz, H-6a); 4.54 (dd, 1H, J.sub.6a,6b 12.0, J.sub.5,6b 5.6 Hz, H-6b); 4.25 (dd, 1H, J.sub.2,3 3.6, J.sub.1,2 1.1 Hz, H-2); 4.01 (dd, 1H, J.sub.3,4 10.2, J.sub.4,5 10.0 Hz, H-4); 4.03-3.96 (m, 1H, H-1a); 3.66-3.58 (m, 1H, H-1b); 3.57 (ddd, 1H, J.sub.4,5 10.0, J.sub.5,6b 5.6, J.sub.5,6a 2.4 Hz, H-5); 1.04-0.92 (m, 2H, 2H-2); 0.01 (s, 9H, Si(CH.sub.3).sub.3).

(57) .sup.13C-NMR (125 MHz, CDCl.sub.3) : 166.4, 165.8 (2 CO); 134.1, 133.5 (2 C-4); 130.3, 130.0 (4 C-2); 129.9 (C-1); 128.9 (2 C-3); 128.8 (C-1); 128.7 (2 C-3); 99.3 (C-1); 74.5 (C-3); 73.0 (C-5); 67.9 (C-1); 64.0 (C-6); 61.8 (C-2); 57.8 (C-4); 18.3 (C-2); 1.2 (Si(CH.sub.3).sub.3).

(58) HRMS (ESI.sup.+): [M+Na].sup.+ (C.sub.25H.sub.30N.sub.6O.sub.6NaSi.sup.+) Calc. 561.1888, found 561.1895.

(59) [].sub.D=50.6 (c 1.0, CHCl.sub.3).

Invention Example 7

Synthesis of 1-trimethylsilylethanyl 3,6-di-O-benzoyl--D-galactopyranoside (5)

(60) ##STR00039##

(61) To a solution of compound 4 (1.17 g, 4.17 mmol, 1.0 eq.) and 2-aminoethyl diphenylborinate (95.0 mg, 0.42 mmol, 0.10 eq.) in dry CH.sub.3CN (21.0 mL, 0.20 M) were added successively N,N-diisopropylethylamine (2.91 mL, 16.7 mmol, 4.0 eq.) and benzoyl chloride (1.93 mL, 16.7 mmol, 4.0 eq.) at 0 C. under an argon atmosphere. The resulting mixture was stirred at 0 C. for 30 minutes then was allowed to warm up at room temperature and stirred for 1 hour. The mixture was then diluted with ethyl acetate, washed with H.sub.2O (30.0 mL), and extracted three times with ethyl acetate. The combined organic layers were washed with Brine, then dried over anhydrous Na.sub.2SO.sub.4, filtered, and concentrated under reduced pressure. The resulting crude material was purified by flash column chromatography over silica gel (Cyclohexane/Ethyl Acetate 90:10 to 70:30) to afford compound 5 (1.54 g, 75%) as a colourless foam. Purity of more than 95% by NMR analysis.

(62) Rf (Cyclohexane/Ethyl Acetate 6:4): 0.47.

(63) IR (cm.sup.1): 1718, 1277, 1117, 1071, 712.

(64) .sup.1H-NMR (exchange with D.sub.2O) (300 MHz, CD.sub.3OD) : 8.16-8.02 (m, 4H, 4H-2); 7.65-7.57 (m, 2H, 2H-4); 7.52-7.43 (m, 4H, 4H-3); 5.03 (dd, 1H, J.sub.2,3 10.1, J.sub.3,4 3.5 Hz, H-3); 4.62 (dd, 1H, J.sub.6a,6b 11.3, J.sub.5,6a 7.8 Hz, H-6a); 4.47 (dd, 1H, J.sub.6a,6b 11.3, J.sub.5,6b 4.8 Hz, H-6b); 4.46 (d, 1H, J.sub.1,2 7.8 Hz, H-1); 4.23 (dd, 1H, J.sub.3,4 3.5, J.sub.4,5 1.0 Hz, H-4); 4.06 (ddd, .sup.1H, J.sub.5,6a 7.8, J.sub.5,6b 4.8, J.sub.4,5 1.0 Hz, H-5); 3.98 (ddd, 1H, J.sub.1a,2a 11.3, J.sub.1a,1b 9.7, J.sub.1a,2b 6.1 Hz, H-1a); 3.93 (dd, 1H, J.sub.2,3 10.1, J.sub.1,2 7.8 Hz, H-2); 3.69 (ddd, 1H, J.sub.1b,2b 11.1, J.sub.1a,1b 9.7, J.sub.1b,2a 6.1 Hz, H-1b); 1.06 (ddd, 1H, J.sub.2a,2b 13.9, J.sub.2a,1a 11.3, J.sub.2a,1b 6.1 Hz, H-2a); 0.98 (ddd, 1H, J.sub.2a,2b 13.9, J.sub.2b,1b 11.1, J.sub.2b,1a 6.1 Hz, H-2b); 0.01 (s, 9H, Si(CH.sub.3).sub.3).

(65) .sup.13C-NMR (125 MHz, CD.sub.3OD) : 168.0, 167.9 (2 CO); 134.5, 134.4 (2 C-4); 131.7, 131.5 (2 C-1); 131.0, 130.7 (4 C-2); 129.8, 129.6 (4 C-3); 104.5 (C-1); 78.1 (C-3); 74.0 (C-5); 70.2 (C-2); 68.3 (C-1); 68.2 (C-4); 65.1 (C-6); 19.2 (C-2); 1.3 (Si(CH.sub.3).sub.3).

(66) HRMS (ESI.sup.+): [2M+Na].sup.+ (C.sub.50H.sub.64O.sub.16NaSi.sub.2.sup.+) Calc. 999.3625, found 999.3680.

(67) [].sub.D=+31.6 (c 1.0, CH.sub.3OH).

Invention Example 8

Synthesis of 1-trimethylsilylethanyl -D-galactopyranoside (4)

(68) ##STR00040##

(69) To a solution of compound 3 (2.15 g, 4.8 mmol, 1.0 eq.) in CH.sub.3OH (25.0 mL, 0.20 M), was added K.sub.2CO.sub.3 (0.10 g, 0.7 mmol, 0.15 eq.) under an argon atmosphere. The reaction mixture was stirred at room temperature for 1 hour. Dowex H.sup.+ resin was added the reaction mixture until neutral pH. The suspension was filtered off, washed with CH.sub.3OH, then the filtrate was concentrated to give compound 4 (1.25 g, 93%) as a white foam. Purity of more than 95% by NMR analysis.

(70) Rf (CH.sub.2Cl.sub.2/CH.sub.3OH 9:1): 0.17.

(71) IR (cm.sup.1): 3380, 1250, 1059, 836.

(72) .sup.1H-NMR (exchange with D.sub.2O) (300 MHz, CD.sub.3OD) : 4.22 (d, 1H, J.sub.1,2 7.0 Hz, H-1); 4.01 (ddd, 1H, J.sub.1a,1b 11.5, J.sub.1a,1b 9.5, J.sub.1a,2a 5.9 Hz, H-1a); 3.82 (dd, 1H, J.sub.3,4 3.0, J.sub.4,5 1.0 Hz, H-4); 3.76 (dd, 1H, J.sub.6a,6b 11.3, J.sub.5,6a 6.7 Hz, H-6a); 3.71 (dd, 1H, J.sub.6a,6b 11.3, J.sub.5,6b 5.5 Hz, H-6b); 3.62 (ddd, 1H, J.sub.1b,2a 11.3, J.sub.1a,1b 9.5, J.sub.1b,2b 6.0 Hz, H-1b); 3.50 (dd, 1H, J.sub.2,3 9.4, J.sub.1,2 7.0 Hz, H-2); 3.49 (ddd, 1H, J.sub.5,6a 6.7, J.sub.5,6b 5.5, J.sub.4,5 1.0 Hz, H-5); 3.45 (dd, 1H, J.sub.2,3 9.4, J.sub.3,4 3.0 Hz, H-3); 1.06 (ddd, 1H, J.sub.2a,2b 13.8, J.sub.2a,1b 11.3, J.sub.2a,1a 5.9 Hz, H-2a); 0.97 (ddd, 1H, J.sub.2a,2b 13.8, J.sub.2b,1a 11.5, J.sub.2b,1b 6.0 Hz, H-2b); 0.03 (s, 9H, Si(CH.sub.3).sub.3).

(73) .sup.13C-NMR (125 MHz, CD.sub.3OD) : 104.6 (C-1); 76.8 (C-5); 75.3 (C-3); 72.7 (C-2); 70.5 (C-4); 68.2 (C-1); 62.7 (C-6); 19.3 (C-2); 1.3 (Si(CH.sub.3).sub.3).

(74) HRMS (ESI.sup.+): [2M+Na].sup.+ (C.sub.22H.sub.48O.sub.12NaSi.sub.2.sup.+) Calc. m/z: 583.2577, found: 583.2586.

(75) [].sub.D=22.3 (c 1.0, CH.sub.3OH).

Invention Example 9

Synthesis of 1-trimethylsilylethanyl 2,3,4,6-tetra-O-acetyl--D-galactopyranoside (3)

(76) ##STR00041##

(77) To a suspension of compound 2 (2.46 g, 5.0 mmol, 1.0 eq.) and trimethylsilylethanol (0.93 mL, 6.5 mmol, 1.3 eq.) in dry CH.sub.2Cl.sub.2 (50.0 mL, 0.10 M), was added TMSOTf (45 L, 0.25 mmol, 0.05 eq.) at 35 C. under an argon atmosphere. The suspension was stirred at 35 C. for 30 min under an argon atmosphere. The reaction mixture was quenched by triethylamine (1.0 mL), then allowed to reach room temperature and concentrated under vacuum. The residue was purified by flash column chromatography over silica gel (Petroleum Ether/Ethyl Acetate 85:15 to 65:35) to afford compound 3 (1.70 g, 76%) as a colourless oil. Purity of more than 95% by NMR analysis.

(78) Rf (Cyclohexane/Ethyl Acetate 6:4): 0.57.

(79) IR (cm.sup.1): 1752, 1221, 772.

(80) HRMS (ESI.sup.+): [M+Na].sup.+ (C.sub.19H.sub.32O.sub.10NaSi.sup.+) Calc. m/z: 471.1657, found: 471.1677.

(81) .sup.1H-NMR (500 MHz, CDCl.sub.3) : 5.36 (dd, 1H, J.sub.3,4 3.5, J.sub.4,5 1.1 Hz, H-4); 5.18 (dd, 1H, J.sub.2,3 10.4, J.sub.1,2 8.0 Hz, H-2); 4.99 (dd, 1H, J.sub.2,3 10.4, J.sub.3,4 3.5 Hz, H-3); 4.46 (d, 1H, J.sub.1,2 8.0 Hz, H-1); 4.18 (dd, 1H, J.sub.6a,6b 11.2, J.sub.5,6a 6.4 Hz, H-6a); 4.10 (dd, 1H, J.sub.6a,6b 11.2, J.sub.5,6b 7.1 Hz, H-6b); 3.97 (ddd, 1H, J.sub.1a,2a 10.9, J.sub.1a,1b 9.6, J.sub.1a,2b 5.3 Hz, H-1a); 3.88 (ddd, 1H, J.sub.5,6b 7.1, J.sub.5,6a 6.4, J.sub.4,5 1.1 Hz, H-5); 3.55 (ddd, 1H, J.sub.1b,2b 10.4, J.sub.1a,1b 9.6, J.sub.1b,2a 6.7 Hz, H-1b); 2.13, 2.03, 2.02, 1.96 (4s, 12H, COCH.sub.3); 0.96 (ddd, 1H, J.sub.2a,2b 13.9, J.sub.2a,1a 10.9, J.sub.2a,1b 6.7 Hz, H-2a); 0.89 (ddd, 1H, J.sub.2a,2b 13.9, J.sub.2b,1b 10.4, J.sub.2b,1a 5.3 Hz, H-2b); 0.01 (s, 9H, Si(CH.sub.3).sub.3).

(82) .sup.13C-NMR (125 MHz, CDCl.sub.3) : 170.6, 170.5, 170.4, 169.6 (4 CO); 101.0 (C-1); 71.3 (C-3); 70.8 (C-5); 69.2 (C-2); 67.8 (C-1); 67.3 (C-4); 61.5 (C-6); 21.0, 20.9, 20.8 (4 COCH.sub.3); 18.2 (C-2); 1.2 (Si(CH.sub.3).sub.3).

(83) [].sub.D=16.2 (c 1.0, CHCl.sub.3).

Invention Example 10

Synthesis of O-(2,3,4,6-tetra-O-acetyl--D-galactopyranosyl)trichloroacetimidate (2)

(84) ##STR00042##

(85) To a solution of compound 1 (6.42 g, 18.4 mmol, 1.0 eq.) in dry CH.sub.2Cl.sub.2 (90.0 mL, 0.20 M) was added trichloroacetonitrile (18.5 mL, 184.4 mmol, 10.0 eq.) and 1,8-diazabicyclo(5.4.0)undec-7-ene (0.55 mL, 3.7 mmol, 0.2 eq.). The reaction mixture was stirred at room temperature for 2 hours. The crude mixture was purified by flash column chromatography over silica gel (Petroleum Ether/Ethyl Acetate 90:10 to 50:50) to afford the compound 2 (6.53 g, 72%) as a white solid. Purity of more than 95% by NMR analysis.

(86) Rf (Cyclohexane/Ethyl Acetate 6:4): 0.49.

(87) IR (cm.sup.1): 1749, 1372, 1224, 1072.

(88) .sup.1H-NMR (500 MHz, CDCl.sub.3) : 8.64 (s, 1H, NH); 6.58 (d, 1H, J.sub.1,2 3.5 Hz, H-1); 5.54 (dd, 1H, J.sub.3,4 3.2, J.sub.4,5 1.3 Hz, H-4); 5.41 (dd, 1H, J.sub.2,3 10.9, J.sub.3,4 3.2 Hz, H-3); 5.34 (dd, 1H, J.sub.2,3 10.9, J.sub.1,2 3.5 Hz, H-2); 4.42 (ddd, 1H, J.sub.5,6b 6.7, J.sub.5,6a 6.7, J.sub.4,5 1.3 Hz, H-5); 4.14 (dd, 1H, J.sub.6a,6b 11.3, J.sub.5,6a 6.7 Hz, H-6a); 4.06 (dd, 1H, J.sub.6a,6b 11.3, J.sub.5,6b 6.7 Hz, H-6b); 2.14, 2.00, 1.99, 1.99 (4s, 12H, COCH.sub.3).

(89) .sup.13C-NMR (125 MHz, CDCl.sub.3) : 170.5, 170.3, 170.3, 170.2 (4 CO); 161.2 (CNH); 93.8 (C-1); 91.0 (CCl.sub.3); 69.2 (C-5); 67.7 (C-3); 67.6 (C-4); 67.6 (C-2); 61.5 (C-6); 20.9, 20.8, 20.7 (4 COCH.sub.3).

(90) [].sub.D=+92.6 (c 1.0, CHCl.sub.3).

Invention Example 11

Synthesis of 2,3,4,6-tetra-O-acetyl-D-galactopyranose (1)

(91) ##STR00043##

(92) To a solution of ethylenediamine (2.24 mL, 2.02 g, 33.5 mmol, 1.1 eq.) in dry THF (61.0 mL, 0.50 M) was added dropwise glacial acetic acid (1.92 mL, 2.01 g, 33.5 mmol, 1.1 eq.) at 0 C. Then, commercially available 1,2,3,4,6-penta-O-acetyl--D-galactopyranoside (11.9 g, 30.5 mmol, 1.0 eq.) was added. The reaction mixture was stirred at room temperature under an argon atmosphere for 2 days. Then the reaction mixture was diluted with CH.sub.2Cl.sub.2 and the mixture was washed successively with HCl solution (1 N), saturated NaHCO.sub.3 solution and Brine. The organic layers were finally dried over anhydrous Na.sub.2SO.sub.4. After filtration, the filtrate was evaporated under vacuum to give a mixture of starting material and compound 1 with a ratio by NMR of 1:14 (10.37 g) as a white foam. This mixture was used without purification in the next step.

(93) Rf (Cyclohexane/Ethyl Acetate 6:4): 0.13.

(94) HRMS (ESI.sup.+): [M+Na].sup.+ (C.sub.14H.sub.20O.sub.10Na.sup.+) Calc. 371.0949, found 371.0941.

(95) Compound 1:

(96) .sup.1H-NMR (500 MHz, CDCl.sub.3) : 5.50 (br d, 1H, J.sub.1,2 3.5 Hz, H-1); 5.45 (dd, 1H, J.sub.3,4 3.3, J.sub.4,5 1.4 Hz, H-4); 5.39 (dd, 1H, J.sub.3,2 10.8, J.sub.3,4 3.3 Hz, H-3); 5.14 (dd, 1H, J.sub.2,3 10.8, J.sub.1,2 3.5 Hz, H-2); 4.45 (ddd, 1H, J.sub.5,6b 6.7, J.sub.5,6a 6.5, J.sub.5,4 1.4 Hz, H-5); 4.10 (dd, 1H, J.sub.6a,6b 11.4, J.sub.6a,5 6.5 Hz, H-6a); 4.06 (dd, 1H, J.sub.6a,6b 11.4, J.sub.6b,5 6.7 Hz, H-6b); 3.12-3.02 (br s, 1H, OH); 2.12, 2.08, 2.03, 1.97 (4 s, 12H, 4 COCH.sub.3).

(97) .sup.13C-NMR (125 MHz, CDCl.sub.3) : 170.7, 170.6, 170.4, 170.2 (4 CO); 90.9 (C-1); 68.5 (C-2); 68.4 (C-4); 67.4 (C-3); 66.5 (C-5); 62.0 (C-6); 21.0-20.7 (4 COCH.sub.3).

(98) Compound 1:

(99) .sup.1H-NMR (500 MHz, CDCl.sub.3) : 5.39-5.37 (br s, 1H, H-4); 5.06-5.04 (m, 2H, H-2, H-3); 4.70-4.65 (br s, 1H, H-1); 4.13 (d, 2H, J.sub.5,6 6.6 Hz, 2H-6); 3.93 (td, 1H, J.sub.5,6 6.6, J.sub.5,4 1.1 Hz, H-5); 3.62-3.55 (br s, 1H, OH); 2.14, 2.08, 2.02, 1.98 (4 s, 12H, 4 COCH.sub.3).

(100) .sup.13C-NMR (125 MHz, CDCl.sub.3) : 170.7, 170.6, 170.4, 170.2 (4 CO); 96.3 (C-1); 71.4, 71.3, 70.5 (C-2, C-3, C-5); 67.4 (C-4); 61.7 (C-6); 21.1-20.7 (4 COCH.sub.3).

(101) The final product 11 was obtained with an overall yield of 8 mol % and with a high purity of more than 95% by NMR analysis.

(102) ##STR00044##

(103) The invention synthesis starts from the commercially available D-galactose pentaacetate and is providing the product of interest 11 with an overall yield of 8 mol %, with a purity of more than 95% by NMR analysis

(104) One skilled in the art will understand that various variations of the conditions of reaction of the invention can be made without departing from the core of the invention, including variations of the concentrations, nature of solvents, temperature, pressure, duration of reaction and stirring. Therefore, the invention covers all technical equivalents of the invention defined by the claims.

REFERENCES CITED

(105) [1] C. Huo, C. Wang, M. Zhao, S. Peng, Chem. Res. Toxicol., 2004, 17 (8), 1112-1120. [2] W. Pilgrim, P. V. Murphy, J. Org. Chem., 2010, 75, 6747-6755. [3] E. Durantie, C. Bucher, R. Gilmour, Chem. Eur. J., 2012, 18, 8208-8215. [4] J. J. Plattner, R. G. Gless, H. Rapoport, J. Am. Chem. Soc., 1972, 94, 8613. [5] D. Lee, M. S. Taylor, J. Am. Chem. Soc., 2011, 133, 3724-3727. [6] Y. E. Tsvetkov, A. S. Shashkov, Y. A. Knirel, U. Zahringer, Carbohydr. Res., 2001, 335, 221-243. [7] J. Mas Pons, A. Dumont, G. Sautejeau, E. Fugier, A. Baron, S. Dukan, B. Vauzeilles, Angew. Chem. Int. Ed., 2014, 53, 1275-1278. [8] K. Jansson, T. Frejd, J. Kihlberg, G. Magnusson, Tetrahedron Lett., 1988, 29, 361-362.