Further Progress Towards the Total Synthesis of Paecilospirone

Abstract

The [5,6]-bisbenzannulated spiroacetal paecilospirone possesses a challenging scaffold that contains the unique spiroacetal structure, and is a viable drug target for its antimitotic properties. This thesis details progress towards a concise, modular synthesis that implements the nickel-catalyzed Suzuki cross-coupling of the ethoxy chromene and arylboronic acid precursors, a reaction which enables late-stage functionalization of the molecular scaffold. Also featured is a DDQ-mediated oxidative spiroacetalization, a method amenable to catalytic asymmetric induction. Initial optimization efforts of the two major low-yielding steps, the construction of 2H-Chromene and the spiroacetal moiety, are discussed. Additionally, we report the mischaracterization of a critical intermediate generated by a NBS halobromination reaction previously published by the Doyle lab. This has prompted a reevaluation of the proposed synthetic route and investigations concerning the revised pathway.