A new synthesis of (–)-anisomycin and its demethoxy analogue from D-ribose

Abstract

2,3-O-Isopropylidene-D-ribose(7) reacted with p-methoxybenzylmagnesium chloride in tetrahydrofuran to give the D-allotriol (6a)(77%). Periodate oxidation of compound (6a) followed by reaction with hydroxylamine hydrochloride in pyridine gave (E,Z)-5-deoxy-2,3-O-isopropylidene-5-(p-methoxy-phenyl)-L-ribose oxime (18a) which was converted into the nitrile methanesulphonate (19a) with methanesulphonyl chloride in pyridine. Reduction of the nitrile (19a) with lithium aluminium hydride gave (2R,3S,4R)-3,4-isopropylidenedioxy-2-(p-methoxybenzyl)pyrrolidine (2a)[45% from (6a)], which was converted into the epoxide (24a)(68%)via the bromo acetates (28a) and (29a). Regioselective opening of the epoxide ring in compound (24a) with acidic allyl alcohol gave the allyl ether (30a)(63%) which was converted into the N-benzyl 3-acetoxy compound (31a)(77%). Removal of the allyl and benzyl groups, by treatment with palladium-charcoal under acidic conditions followed by hydrogenolysis, gave (–)-anisomycin (1a)(86%).

A similar series of reactions afforded demethoxyanisomycin (1b) which showed antibiotic activity against Trichomonas vaginalis[about one sixth the activity of anisomycin (1a)].