Dichloromethylenation of sugar γ-lactones: a stereospecific synthesis of L-(+)-muscarine and L-(+)-epimuscarine toluene-p-sulphonates

Abstract

Treatment of di-isopropylidene-D-mannono-1,4-lactone (3) with hexamethylphosphorous triamide–tetrachioromethane gave the dichloro-olefin (4), which was converted into the ketone (5) by treatment with lithium di-isopropylamide. Reduction with Raney nickel gave the key intermediate (7) together with its isomer (6)(9:1 ratio). Compound (7) was transformed into L-(+)-epimuscarine (2)via glycol cleavage, reduction, tosylation, and treatment with trimethylamine. L-(+)-Muscarine (1) was synthesised from compound (7) by inversion of the hydroxy group configuration at C-3 followed by the above sequence.