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

Abstract

Abstract A 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.