Total Synthesis of Ganoderma Meroterpenoids Cochlearol B and Its Congeners Driven by Structural Similarity and Biological Homology.

ABSTRACT

Secondary metabolites that have the same biological origin must share some relationship in their biosynthesis. Exploring this relationship has always been a significant task for synthetic biologists. However, from the perspective of synthetic chemists, it is equally important to propose, prove, or refute potential biosynthetic pathways in order to elucidate and understand the biosynthesis of homologous secondary metabolites. In this study, driven by the high structural similarity between the homologous Ganoderma meroterpenoids cochlearol B and ganocin B, two chemically synthetic strategies were designed and investigated sequentially for the synthesis of cochlearol B from ganocin B. These strategies include intramolecular metal-catalyzed hydrogen atom transfer (MHAT) and intramolecular photochemical [2+2] cycloaddition. The aim was to reveal their potential biosynthetic conversion relationship using chemical synthesis methods. As a result, a highly efficient total synthesis of cochlearol B, cochlearol T, cochlearol F, as well as the formal total synthesis of ganocins A-B, and ganocochlearins C-D, has been achieved. Additionally, a novel synthetic approach for the synthesis of 6,6-disubstituted 6H-dibenzo[b,d]pyran and its analogues has been developed through palladium(II)-catalyzed Wacker-type/cross-coupling cascade reactions.