We propose to develop methods for the synthesis of alkaloids and optically active steroids by means of cycloadditions with alkenylammonium salts, a class of compounds almost totally uninvestigated to date. There exist no good methods today for the addition of dialkylamino-substituted dienophiles in cycloadditions, even though this synthetic process would be of great value in alkaloid total synthesis. The new general methods described herein would allow this synthetic scheme to be carried out easily, thereby making several natural products and synthetic intermediates very readily available in only a few steps. Moreover, the use of optically active, structurally rigid alkenylammonium salts would permit facile asymmetric induction in Diels-Alder cycloadditions, a process which can be accomplished well only rarely today. Our mew methods would allow us to prepare important, medicinally active natural products, such as the antitumor and antimicrobial antibiotic lavendamycin and the antileukemic agents precriwelline and pretazzettine, as well as optically active intermediates for the synthesis of Vitamin D3 and optically active amino acids. Preparation of these compounds and their structural analogues by our efficient routes would make them available in sufficient amounts to permit the necessary testing to evaluate their chemotherapeutic potential. Finally, these methods could be applied to the synthesis of other medicinally active alkaloids.
