Total synthesis and revision of stereochemistry of the marine metabolite trunkamide A.
The isolation of the cytotoxic Lissoclinum sp. metabolite trunkamide A was reported in 1996. After completion of a total synthesis in 1999, it became clear that the structure of this marine natural product had to be revised. We now report the first preparation of actual trunkamide A in a total synthesis that serves as an unambiguous structural and stereochemical proof. Highlights of our synthetic strategy are a Lewis acid assisted aziridine opening that was used for the preparation of the novel reverse-prenylated serine and threonine side chains as well as an efficient oxazoline-thiazoline interconversion on the macrocyclic skeleton. In addition, several stereoisomers prepared by complementary synthetic protocols serve to illustrate the general scope of our methodology and confirm the configurational assignment.
Wipf
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Department of Chemistry, University of Pittsburgh, Pennsylvania 15260, USA.
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D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D014561:Urochordata / Q000737:chemistry*
D000470:Alkaloids; D010456:Peptides, Cyclic; C414110:trunkamide A