title: Synthesis of 2,6,7-trideoxy-7-C-(2,4-dichlorophenyl)-D-xylo-heptonic acid and 6-(2,4-dichlorophenyl)-D-xylo-2,3,4-tri-hydroxyhexanesulfonic acid.
abstract: 2,4-O-Benzylidene-L-xylose was converted via a Wittig reaction into Z-2,4-O-benzylidene-5,6-dideoxy-6-C-(2,4-dichlorophenyl)-D-xylo-hex-5-++ +enitol (17), which, on hydrogenation, gave 5,6-dideoxy-6-C-(2,4-dichlorophenyl)-D-xylo- hexitol (33). tert-Butyldimethylsililation of the primary hydroxyl group of 33, followed by 4-methoxybenzylation, and desilylation afforded 5,6-dideoxy-6-C-(2,4-dichlorophenyl)-2,3,4-tri-O-(4-methoxybenzyl)-D-xyl o- hexitol (54). A Mitsunobu-type reaction of 54 replaced HO-1 by cyanide to give, after hydrolysis and hydrogenolysis, 2,6,7-trideoxy-7-C-(2,4- dichlorophenyl)-D-xylo-heptono-1,4-lactone (55). Mesylation of 33 and then acetylation gave 2,3,4-tri-O-acetyl-5,6-dideoxy- 6-C-(2,4-dichlorophenyl)-1-O-methanesulfonyl-D-xylo-hexitol (63), which was converted via its 1-thiobenzoate into bis[1,5,6-trideoxy-6-C-(2,4-dichlorophenyl)-D-xylo-hexitol] 1,1'-disulfide (65). Acetylation of 65, followed by permanganate oxidation and deacetylation, afforded sodium 6-(2,4-dichlorophenyl)-D-xylo- 2,3,4-trihydroxy-hexanesulfonate (67). Both 57 (obtained from 55 by hydrolysis with NaOH) and 67 are weak inhibitors of HMG-CoA reductase.
authors.affiliation: Institute for Drug Research, Budapest, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Kuszmann
authors.forename: B
authors.initials: B
authors.lastname: Podányi
mesh_terms: D006538:Heptanoic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013451:Sulfonic Acids / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013451:Sulfonic Acids; C076015:6-(2,4-dichlorophenyl)-2,3,4-trihydroxyhexanesulfonic acid; C076014:2,6,7-trideoxy-7-C-(2,4-dichlorophenyl)heptonic acid