Pseudosugars, 32. – Synthesis of 1,4‐Imino‐linked Carbadisaccharides Composed of a 2‐Amino‐5a‐carba‐2‐deoxyglucopyranosylamine Residue and Its Congeners

Abstract

AbstractCarbadisaccharide 5, containing a 2‐acetamido‐5a‐carba‐2‐deoxyhexopyranosylamine residue, was synthesized by coupling of methyl 4‐amino‐4‐deoxy‐α‐D‐glucopyranoside (41) with the N‐(2,4‐dinitrophenyl)epimino compound 16 followed by deprotection. The 6′‐acetamido‐6′‐deoxy analog 3 of a potent α‐glucosidase inhibitor methyl acarviosin (1) was synthesized from a condensate 50 obtained by coupling of 41 with the protected epimino compound 18, possessing an exo‐methylene function. This process involves a sequence of reactions: replacement by a benzoate ion and successive dehydrobromination of the dibromide 52 obtained from 50. Hydroxymercuration of 50 followed by demetalation and deprotection gave two carbadisaccharide analogs 7 and 9 containing the valiolamine‐type branched aminocyclitol moieties. The free amines 4, 6, 8, and 10 were prepared by treatment of the corresponding N‐protected derivatives with Amberlite IRA 400 (OH−) resin. Biological assays of all carbadisaccharides were carried out with three sugar hydrolases. Only compounds 6 and 8 were shown to be very weak α‐mannosidase inhibitors. The introduction of the acetamido or amino function instead of the hydroxyl group into the C‐6′ position of the methyl acarviosin analog 2 resulted in an appreciable decrease of the inhibitory activity.