Synthesis and Determination of the Absolute Configuration of the Bicyclic Guanidine Core of Batzelladine A and the Development of a Novel [4+2] Inverse Electron Demand Hetero Diels -Alder Cycloaddition and Its Application Toward the Synthesis of the Tricyclic Guanidine Fragment Within Batzelladine A

Abstract

Our developments toward the total synthesis batzelladine A are presented in this study. This includes the construction of the bicyclic guanidine portion including elucidation of the absolute configuration of the bicyclic guanidine and the development of a novel [4+2] inverse electron demand hetero Diels-Alder cycloaddition amendable for synthesis of the tricyclic guanidine portion. These studies culminated in the first synthesis of the bicyclic guanidine core within batzelladine A, which was demonstrated by accessing in enantiospecific fashion a suitably protected form of the bicyclic core employing L -aspartic acid as the starting material. The development of a novel strategy for accessing the tricyclic guanidine portion within batzelladine A is also included within this study. We have identified a novel [4+2] inverse electron demand hetero Diels-Alder cycloaddition between alpha,beta-unsaturated carbodiimides and cyclic thioimidates for access to functionalized guanidines which were shown to be possible advanced intermediates for the functionalized tricyclic guanidine contained within batzelladine A.