The Paradox of Antimalarial Terpenoid Isonitrile Biosynthesis Explained. Proposal of Cyanoformate as an NC Delivery Vector.

ABSTRACT: Marine sponge diterpenoid isonitriles are exceptional nitrogenous natural products that exhibit antiplasmodial activity. Their biosynthesis presents a biosynthetic puzzle: how do the elements of NC engage terpenyl carbocations in isoprenoid secondary metabolism, and what is the biosynthetic precursor of the NC group? Cyanoformic acid (NC-COOH, B1) is proposed as a plausible delivery vehicle of NC that resolves a paradox in the commonly held proposition that an inorganic cyanide anion, CN^-, terminates terpenoid isonitrile (TI) biosynthesis. DFT calculations of NC-COOH and its conjugate base, cyanoformate, NC-COO^- (B2), support high nucleophilicity at N and explain bond-forming constitutionality: attack at N and formation of an isonitrile over its nitrile

SUBMITTER: Molinski TF 

PROVIDER: S-EPMC11773565 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature