Synthetic studies related to mycobactins. III. Approaches to the synthesis of the cobactin ring system

Abstract

The synthesis of several seven-membered cyclic hydroxamic acids has been carried out in low yield. Reduction of diethyl 2-hydroxyiminoheptane-l,7-dioate afforded ethyl 1-hydroxy-7-oxohexahydroazepine-2-carboxylate, together with related acyclic products. The cobactin precursor 3-bromo-1-hydroxyhexahydro-azepin-2-one was obtained by the ring expansion of 2-bromocyclohexanone with benzenesulphonohydroxamic acid and also by the peracid oxidation of 6-bromo-7-ethoxy-3,4,5,6-tetrahydro-2H-azepine. The methyl and cinnamyl imidates of hexanolactam were oxidized by peracid to 1-hydroxyhexahydroazepin-2-one, in addition to the related imino- and nitroso-hexanoic esters. In a similar reaction, 1-hydroxypiperidin-2-one was obtained from 2-methoxy-3,4,5,6-tetrahydropyridine. During the course of these oxidation reactions, the intermediate oxaziridines 7-methoxy-8-oxa-1-azabicyclo[5,1,0]octane and 6-bromo-7-ethoxy-8-oxa-1-azabicyclo[5,1,0]octane were isolated and identified. The peraoid oxidation of ethyl N-cyclohexylbenzimidate yielded cyclohexylhydroxylamine and ethyl benzoate in reasonable yields. This reaction suggests a useful method for the conversion of a primary amine into the related hydroxylamine.