The Paradox of Antimalarial Terpenoid Isonitrile Biosynthesis Explained. Proposal of Cyanoformate as an NC Delivery Vector
Year: 2024
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide 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 isomer. TI biogenesis is compared to the cyanoformamide-containing ceratamines that arise from oxidation of a terminal N -Gly amide precursor. A unifying model links C-NC vs C-CN bond formation and places Gly at the center of both biosynthetic schemes.
Source: Journal of Natural Products
Author: Tadeusz F. Molinski
Institution: University of California San Diego
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
OpenAlex ID: W4405638607