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Kibdelones: Novel Anticancer Polyketides from a Rare Australian Actinomycete
Author(s) -
Ratnayake Ranjala,
Lacey Ernest,
Tennant Shaun,
Gill Jennifer H.,
Capon Robert J.
Publication year - 2007
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200601236
Subject(s) - hydroquinone , quinone methide , quinone , chemistry , stereochemistry , cytotoxicity , enol , ring (chemistry) , polyketide , redox , combinatorial chemistry , biochemistry , biosynthesis , organic chemistry , in vitro , catalysis , enzyme
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.