Sugar enolones, XIX. An approach to actinospectose‐type 2,3‐diketo sugars. – Synthetic proof for the R configuration of “Herzgift‐Methylreduktinsäure”︁

Abstract

AbstractA stereochemically defined, preparatively satisfactory access is described to stable derivatives of D‐actinospectose, a 4,6‐dideoxy‐D‐glycero‐hexopyranos‐2,3‐diulose (3a ⇌ 3b) realized in spectinomycin (1) and a series of Calotropis cardenolides (2). Key steps are the conversions of the 6‐deoxy‐D‐hydroxyglucal ester 8 either into the hexulose tribenzoate 10 (47%) by chlorination and hydrolysis, or into the α‐ulosyl bromide 12 (76%) via NBS bromination in the presence of methanol. The suitability of 12, as well as of the actinospectosyl chloride 6, for β‐selective introduction of the actinospectosyl moiety is demonstrated by silver carbonate‐promoted glycosylation and subsequent β‐elimination (12 → 14, 15), resulting in annulation (6 → 16) when reacted with diols. – Reduction of the free carbonyl function of the dibenzoylactinospectose 13 with zinc tetrahydroborate is followed by 3‐O → 2‐O‐benzoyl migration and β‐elimination to afford the stable benzoate 5 of “Herzgift‐Methylreduktinsäure”. The rotational and chiroptical data of 5 furnish unequivocal synthetic proof for the D (or R) configuration of the methyl‐bearing C‐5′ in Calotropis cardenolides.