Synthetic Studies toward Pyruvate Acetal Containing Saccharides. Synthesis of the Carbohydrate Part of the Mycobacterium smegmatis Pentasaccharide Glycolipid and Fragments Thereof for the Preparation of Neoantigens

Article abstract of DOI:10.1021/jo00057a021

A series of 2,3-di-O-benzoyl-4,6-O-<(S)-1-(methoxycarbonyl)ethylidene>-D-glucopyranosyl donors (β-phenylthio 3, bromide 4, α-chloride 5, β-fluoride 6, and trichloroacetimidate 7) were prepared from the corresponding α-allyl glucoside 1 via the deallylated glucose 2 and were tested in glycosylation reactions with methanol to give the pyruvylated methyl glucosides 8 and 9 and with methyl 2,4,6-tri-O-benzoyl-β-D-glucopyranoside 10 to give the disaccharide 11.Best result with respect to yield and β-selectivity of the coupling were achieved with imidate 7.Thus, the 2-O-benzoyl-4,6-O-<(S)-1-(methoxycarbonyl)ethylidene>-3-O-methyl-D-glucopyranosyl trichloroacetimidate 14 was prepared from its benzyl glucoside 12 and used for the synthesis of fragments related to the Mycobacterium smegmatis lipopentasaccharide.Trimethylsilyl trifluoromethanesulfonate-mediated condensation of 14, 5-<(benzyloxycarbonyl)amino>pentanol, and 10, respectively, followed by deblocking of the products 15 and 17 gave the pyruvylated aminopentyl glucoside 16 and methyl laminaribioside 18.Treatment of 17 with dichloromethyl methyl ether gave the laminaribiosyl chloride 19, coupling of which with protected 5-aminopentanol gave 20 also obtained from 14 and the monosaccharide nucleophile 26.The trisaccharide 5-aminopentyl glycoside fragment 42 was prepared by first coupling of 14 and benzyl 2-O-benzoyl-4,6-O-<(S)-1-(methoxycarbonyl)ethylidene>-α-D-glucopyranoside 30 that was converted to the bispyruvylated laminaribiose imidate 33, followed by condensation with thioglycoside 38 obtainable in four steps from 1,2,4,6-tetra-O-acetyl-3-O-benzyl-β-D-glucopyranose to give the trisaccharide ethyl thioglycoside 40.Next, NIS-mediated condensation of 40 and 5-<(benzyloxycarbonyl)amino>pentanol followed by deblocking gave 42.Pentasaccharide 45 was similarly prepared from 40 and hepta-O-benzoyltrehalose 43 to give first the blocked saccharide 44, deblocking of which afforded the target pentasaccharide.