Kibdelones: Novel Anticancer Polyketides from a Rare Australian Actinomycete

Abstract

The kibdelones are a novel family of bioactive heterocyclic polyketides produced by a rare soil actinomycete, Kibdelosporangium sp. (MST-108465). Complete relative stereostructures were assigned to kibdelones A-C (1-3), kibdelone B rhamnoside (5), 13-oxokibdelone A (7), and 25-methoxy-24-oxokibdelone C (8) on the basis of detailed spectroscopic analysis and chemical interconversion, as well as mechanistic and biosynthetic considerations. Under mild conditions, kibdelones B (2) and C (3) undergo a facile equilibration to kibdelones A-C (1-3), while kibdelone B rhamnoside (5) equilibrates to a mixture of kibdelone A-C rhamnosides (4-6). A plausible mechanism for this equilibration is proposed and involves air oxidation, quinone/hydroquinone redox transformations, and a choreographed sequence of keto/enol tautomerizations that aromatize ring C via a quinone methide intermediate. Kibdelones exhibit potent and selective cytotoxicity against a panel of human tumor cell lines and display significant antibacterial and nematocidal activity.

Arixanthomycins A–C: Phylogeny-Guided Discovery of Biologically Active eDNA-Derived Pentangular Polyphenols

“…21–23 In these known metabolites, the oxazolidine rings would appear to arise from the incorporation of an ethanolamine and therefore the carboxylate is not present. While sugars are seen on some pentangular polyphenols, 23–25 no previous reports of a C-13 glycosylation appear in the literature.…”

Enantioselective Halolactonization Reactions using BINOL-Derived Bifunctional Catalysts: Methodology, Diversification, and Applications

“…19 Collectively, compounds belonging to this class possess an array of potentially useful biological activities that include low nanomolar GI 50 ’s against a panel of human cancer cell lines as well as potent antibacterial and nematocidal properties. The promising biological activity of 65 coupled with its complex polycyclic architecture sparked considerable interest in the synthetic community, culminating in two successful enantioselective syntheses, (+)-kibdelone C completed by Porco, 20 and (−)-kibdelone C completed by Ready.…”

New antibiotic structures from fermentations

“…Kibdelone A (20) showed better activity and displayed LD 99 values of 0.084 and 2.7 nM against B. subtilis and E. coli, respectively. The dihydro compound kibdelone B (21) showed no activity against E. coli and was about twofold less active against B. subtilis (LD 99 0.13 nM) [31].…”