Biomimetic Total Synthesis of Bisorbicillinol, Bisorbibutenolide, Trichodimerol, and Designed Analogues of the Bisorbicillinoids

Abstract

The bisorbicillinoids are a growing class of novel natural products endowed with unique biological activity and are associated with fascinating hypotheses for their biosynthesis. A full account of our biomimetic explorations toward the bisorbicillinoids including the total syntheses of bisorbicillinol ( 1 ), bisorbibutenolide ( 2 ), and trichodimerol ( 4 ) from sorbicillin ( 3 ) is disclosed. Utilizing the novel dimerization reactions discovered and fine-tuned en route to 1 and 4, several analogues of these natural products have been synthesized. Furthermore, studies on the scope of these novel cycloaddition reactions and the isolation of a number of unexpected products along with proposed mechanisms for their formation are reported. These findings add to our knowledge of the largely unexplored chemistry of o -quinols and related aromatic systems.