Studies of the Cyclic Amidoacetal Carbamate Moiety of the Maytansinoids

Article abstract of DOI:10.1021/jo01296a021

A synthesis of cyclic urethane amidoacetals of the type present in the maytansinoid ansa macrolides is reported both to serve as a synthetic model and to explore the chemistry of the hydroxylated intermediates of structures 5 and 6.These compounds are prepared by aldol cyclization of the open-chain amidoacetal aldehyde 4e.Compound 5 is the product of kinetic control, which rearranges to the stable isomeric end products 6 and 7, the latter of which possesses a five-membered urethane ring.The elucidation of structure, stereochemistry, and conformation of these substances is described.The removal of the secondary hydroxyl group of 5 to form 17a is accomplished in three steps.