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

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2024-12-20 DOI:10.1021/acs.jnatprod.4c01295

Tadeusz F Molinski

引用次数: 0

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 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.

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.