The object of this proposal is the total synthesis of axinellamine A, a member of a class of compounds that has shown anti-cancer activity. The synthesis is based around using a key intramolecular [3+2] azomethine ylide cyclization to form the very densely functionalized octahydro cyclopenta pyrole core. Some of the difficult problems in the synthesis to be addressed include the five stereogenic centers on the one ring, two guanidine rings and the introduction of two dibromopyrrole carboxylamides. The goals of this proposal will include: 1) Synthesis of a cyclization substrate based on a asymmetric Diels-Alder reaction 2) Studying the key issues of the azomethine ylide cyclization, which are the reactivity of the dipolarophile, the generation and reactivity of the dipole, and the stereochemistry of the cyclization. 3) Synthesis of the final product and 4) Determination of the absolute configuration of the molecule. The synthesis of this molecule would be an important contribution to a growing class of natural products.
