Synthesis of monomeric post-iboga alkaloids

Abstract

We coined the term “post-iboga” alkaloids for secondary metabolites that are biosynthetically downstream of iboga-type alkaloids with rearranged indole and/or isoquinuclidine scaffolds. We took one step further and categorized the post-iboga alkaloids into five types based on their mode of biosynthetic derivatization from the iboga framework. While there have been extensive synthetic studies on type I post-iboga alkaloids with a cleaved C16−C21 bond from the iboga scaffold exemplified by vinblastine and cleavamine, syntheses of other types of post-iboga alkaloids have remained underdeveloped. We disclose the synthetic studies that led to the synthesis of type II post-iboga alkaloids voatinggine and tabertinggine with a cleaved N4−C21 bond from the iboga scaffold. Furthermore, we delineate full details that enabled the first synthesis of chippiine/dippinine-based type III post-iboga alkaloid dippinine B and dippinine C.