Nature synthesizes various secondary metabolites from a common precursor as a means of maximizing the number of natural products, thus generating and retaining chemical diversity at low cost. By taking advantage of this rule, we accomplished the divergent total syntheses of ten pentacyclic cytochalasans and merocytochalasans from a common precursor aspochalasin D based on structure network analysis of the cytochalasans biosynthetic pathways. The key steps of the syntheses include Prins-type and ene-type cyclizations to establish the core of pentacyclic aspochalasans. Here we report a bioinspired modular syntheses of a suite of merocytochalasans by taking advantage of a biomimetic [5+2] heterocycloaddition of an ortho-quinone intermediate. The synthetic efforts provide a platform for the synthesis of more than 400 valuable cytochalasans bearing different macrocycles and amino-acid residues.

Bioinspired network analysis enabled divergent syntheses of pentacyclic cytochalasans and merocytochalasans

ACS Spring Meeting 2021

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