An Access to the Bicyclic Nucleus of the Sponge Alkaloid Halicyclamine A by Successive Condensation of Malondialdehyde Units, Aldehyde Derivatives, and Primary Amines

Article abstract of DOI:10.1021/jo034099e

First results of an evaluation of the synthetic sequence depicted in Scheme 4 are reported. This sequence is based upon biosynthetic considerations concerning the manzamine family of sponge alkaloids. Stable equivalents 21 and 31 of the tetraaldehyde 7 have thus been obtained by using the chemistry of malondialdehyde previously reported by Tietze. These compounds afforded pyridinium salts 23 and 33 when treated with a primary amine in acidic medium. Further reductive amination and cyclization yielded bicyclic derivatives 25 and 35, thus demonstrating the feasibility of this synthetic approach for the preparation of halicyclamine derivatives 13. Products resulting from cycloaddition reactions leading to 9 were not observed.