Yukihiko Kameda

A new method for selective N-acylation of aminoglycoside antibiotics

Abstract Per- N -formylation of aminoglycoside (aminocyclitol) antibiotics followed by mild hydrolysis with aqueous ammonia gave mono- N -deformylated derivatives. Each positional isomer of the mono- N -deformylated derivatives thus obtained was separated by column chromatography on Amberlite CG-50 (NH 4 + ). Acylation of mono- N -deformylated derivatives gave the corresponding mono- N -acylated derivatives. The N -formyl groups of the mono- N -acylates were removed by the treatment with dilute aqueous hydrazine acetate, whereas the newly introduced N -acyl group was stable under these conditions. The 1- N -formyl group of the deoxystreptamine moiety of per- N -formylated aminoglycoside antibiotics containing neamine (or 3′-deoxyneamine) is more readily deformylated than the 3- N -formyl group. In this report, isolation and structural-elucidation studies, including 13 C-n.m.r. spectral assignments, of positional isomers of tri- N -formyl derivatives of xylostasin ( 1 ), 3′-deoxyxylostasin ( 2 ), kanamycin A ( 3 ), and neamine ( 4 ) are described. This selective N -acylation provides a useful method for the preparation of 1- N -modified derivatives, and the synthesis of 3′-deoxybutirosin A ( 2f ) from 2 is described in detail as an example.