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Nocardiopsins: New FKBP12‐Binding Macrolide Polyketides from an Australian Marine‐Derived Actinomycete, Nocardiopsis sp.
Author(s) -
Raju Ritesh,
Piggott Andrew M.,
Conte Melissa,
Tnimov Zakir,
Alexandrov Kirill,
Capon Robert J.
Publication year - 2010
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.200902933
Subject(s) - racemization , pharmacophore , derivatization , stereochemistry , click chemistry , pipecolic acid , biology , natural product , chemistry , biochemistry , combinatorial chemistry , amino acid , organic chemistry , high performance liquid chromatography
A marine‐derived actinomycete, Nocardiopsis sp. (CMB‐M0232), obtained from a sediment sample collected at a depth of 55 m off the coast of Brisbane, Australia, yielded two new macrolide polyketides. Structures for nocardiopsins A and B were assigned by detailed spectroscopic analysis, degradation and chemical derivatization. A Marfey’s analysis revealed an unexpected acid‐mediated partial racemization of the L ‐pipecolic acid incorporated within the nocardiopsins. The scope of this racemization was assessed against a selection of natural and synthetic N ‐acyl pipecolic acids. While the nocardiopsins are not antibacterial, antifungal or cytotoxic, they do exhibit low‐micromolar binding to the immunophilin FKBP12, consistent with their structural and biosynthetic relationship to the immunosuppressive agents FK506 and rapamycin. The nocardiopsins represent a new point of entry into what has been a valuable, exclusive and reclusive region of bioactive chemical space—that surrounding the FK506/rapamycin pharmacophore.