A Shorter Synthesis of Muscimol

Abstract

The naturally occurring zwitterionic alkaloid muscimol 3 ¹ has been of considerable pharmacological interest in recent years, it being the best example of an in vivo active mimetic of the neurotransmitter γ-aminobutyric acid (GABA).² A number of syntheses of this compound have been reported over the past fourteen years, culminating in the recent report of Jager and Frey who prepared 1 in three steps and 30% overall yield.³ These latter authors suggested the shorter two step

route depicted in Equation 1 but were apparently unable to synthesize the requisite hydroxamic acid 2 in adequate yield and purity to complete the synthesis. The original preparation of this hydroxamic acid had been reported by Hines and Stammer in 1977′ from dimethyl acetylenedicarboxylate and hydroxylamine. This procedure also gave a relatively crude and low melting product.