Total Chemical Synthesis Peers into the Biosynthetic Black Box

摘要

The structures, endemic roles, biosynthetic origins, and chemical reactivities of complex natural products contribute to their allure as enduring subjects of scientific inquiry (7). Embedded in each molecular framework is an evolutionary history, a functional role to be unveiled in a complex biological milieu, and deep mystery with respect to the reaction sequences that might lead to the assembly of the structure, either in nature or in the laboratory (2). Such is the narrative in the study by Kim et al. on page 238 of this issue (5). The authors have achieved a chemical synthesis of the highly complex molecule (+)-ll,H'-dideoxyverticillin A (see the figure), a natural product isolated from the fungus Shiraia bambusicola (4) that possesses anticancer activity (5). Their laboratory synthesis, inspired by an analysis of the possible biosynthetic route, reveals much about chemical reactivity in a highly complex molecular environment.