A Macrocyclic Approach to Tetracycline Natural Products. Investigation of Transannular Alkylations and Michael Additions

Abstract

A new approach to the tetracycline core structure is presented. The pivotal intermediate is identified as macrocycle III. The two interior bonds (C4a-C12a and C5a-C11a) are to be constructed through sequential transannular Michael additions (III-II) and compression-promoted transannular isoxazole alkylations from intermediate II.