Veronique Barberousse

The crystal and molecular structures of 4-cyanophenyl 1,5-dithio-β-d-xylopyranoside S-5 oxide and 4-ethyl-2-oxo-2H- 1-benzopyran-7-yl 5-thio-β-d-xylopyranoside S-5 oxide

Abstract Crystals of 4-cyanophenyl 1,5-dithio-β- d -xylopyranoside S-5 oxide (1) and 4-ethyl-2-oxo-2H-1-benzopyran-7-yl 5-thio-β- d -xylopyranoside S-5 oxide (2) are monoclinic, space group P21, with two independent thioxylosides molecules in the asymmetric unit. The unit cell dimensions are α = 26.385, b = 5.934, c = 8.902 A, and β = 109.90 ° for 1 and α = 16.033, b = 16.676, c = 6.459 A, and β = 91.26 ° for 2. The present work provides structural information on the influence of substitution of intracyclic and glycosidic oxygen atoms by sulfur atoms, as well as on the influence of aromatic rings and of sulfoxide groups on the carbohydrate moiety. In both molecules, the xylopyranosides rings have the classical4C1 conformation. For 1, the orientation of the phenyl substituent with respect to the xylopyranose is very similar in the two independent molecules: the φ and ψ torsion angles are respectively: (−99.5°, 153.8°) and (−102.1°, 154.2°). This is not the case for 2, for which these values are strikingly different: (− 79.4°, 172.1°) and (− 130.2°, −178.4°). In each structure, the molecules are hydrogen bonded within a network of infinite chains.

New 1-C-(5-thio-D-xylopyranosyl) derivatives as potential orally active venous antithrombotics.

In the search for new orally active antithrombotic drugs that are metabolically stable, we explored the synthesis of 1-C-(5-thio-D-xylosyl) derivatives, examining radical and nucleophilic methods. Thus synthesized were aryl, benzyl, alkylcarboxymethylenyl, arylsulfonylmethylenyl and alkylaminocarboxymethylenyl C-linked analogues of 5-thio-D-xylopyranosides.

AN IMPROVED SYNTHESIS OF AN UMBELLIFERYL 5-THIOXYLOPYRANOSIDE, PRECURSOR OF THE ANTITHROMBOTIC DRUG ILIPARCIL

4-Ethyl-2-oxo-2H-1-benzopyran-7-yl 2,3,4-tri-O-acetyl-5-thio-beta-D-xylopyranoside, a synthetic intermediate of the orally active antithrombotic compound Iliparcil, has been prepared in 44-47% isolated yield. Different conditions were used for the glycosylation of 4-ethyl-2H-7-hydroxy-1-benzopyran-2-one 6 applying 2,3,4-tri-O-acetyl-5-thio-D-xylopyranosyl bromide (2), the analogous beta-chloride 3 or the alpha-trichloroacetimidate 5 as donors. With halides 2 and 3, the reaction was carried out in the presence of ZnO-ZnCl2 or ZnO alone. Both promoters are cheap, safe and therefore compatible with large-scale industrial processes.

Synthesis of the 2- and 4-monomethyl ethers and the 4-deoxy-4-fluoro derivative of 4-cyanophenyl 1,5-dithio-β-d-xylopyranoside as potential antithrombotic agents

Abstract The title glycoside undergoes acetonation with 2-methoxypropene to give a 2:1 mixture of the crystalline 2,3- and 3,4-isopropylidene acetals in 94% yield, which upon methylation under controlled conditions followed by deacetonation afforded the respective 4- and 2-monomethyl ethers. The 2,3-acetal underwent reaction with diethylaminosulfur trifluoride to introduce fluorine at C-4 with net retention of stereochemistry, but the 3,4-acetal under comparable conditions underwent migration of the arylthio group to C-2 and fluorination at C-1, with stereochemical retention at both positions.

Synthesis of the 3-methyl ether and 4-deoxy derivatives of 4-cyanophenyl 1,5-dithio-β-d-xylopyranoside (Beciparcil)

Treatment of the 2,3-isopropylidene acetal of the title dithioxyloside with 2,4,5-triiodoimidazole-PPh3 caused replacement of the 4-hydroxyl group by iodine to afford 82% of the 4-axial iodide 6, converted by base into 4-cyanophenyl 2,3-O-isopropylidene-1,5-dithio-beta-D-glycero-pent-3-enopyranoside++ + (8). Acid treatment of 8 gave 87% of the deacetonated glycos-3-ulose, borohydride reduction of which afforded 63% of 4-cyanophenyl 4-deoxy-1,5-dithio-alpha-L-threo-pentopyranoside (3), together with 27% of the 3-axial epimer. The 3-methyl ether of the title dithioxyloside was satisfactorily prepared via 2,4-protection as the cyclic phenylboronate, methylation, and deprotection; alternative strategy via the 2,4-bis(triisopropylsilyl) ether was complicated because of silyl-group migration under methylation conditions.

Chemical interconversions of 4-cyanophenyl 1,5-dithio-β-d-xylopyranoside (Beciparcil®): structural modification at the C-4 position

Abstract The title dithioxyloside 1 , an orally active antithrombotic agent, as its 2,3-isopropylidene acetal, was converted into the corresponding glycos-4-ulose, which served as precursor via reduction to the 4-epimer of 1 and via oximation–reduction to the 4-acetamido-4-deoxy 4-epimer of 1 .