Diastereoselective reduction of cyclic bioactive Mannich ketones

The reduction of cyclic Mannich ketones having antibacterial activity showed poor stereoselectivity with L-Selectride®, sodium trimethoxyborohydride and diisobutylaluminium hydride, while lithium aluminium hydride and, in particular, sodium borohydride often yielded a single stereoisomer. The size of the ring strongly influenced the stereocomposition of the reaction mixtures. An increased preference for the trans isomer was attributed to a weak intramolecular hydrogen bond between the OH and the N, as demonstrated by X-ray crystallography. After reduction, the antibacterial activity of the product decreased dramatically ("S-form") but was not completely abolished in deep rough mutants of Gram-negative bacteria.