Wewakazole, a Novel Cyclic Dodecapeptide from a Papua New Guinea

ORGANIC LETTERS

Wewakazole, a Novel Cyclic Dodecapeptide from a Papua New Guinea Lyngbya majuscula

2003 Vol. 5, No. 1 3-6

Lisa M. Nogle, Brian L. Marquez, and William H. Gerwick* College of Pharmacy, Oregon State UniVersity, CorVallis, Oregon 97331 [email protected] Received August 28, 2002

ABSTRACT

Phytochemical examination of a Papua New Guinea collection of Lyngbya majuscula resulted in the discovery of wewakazole (1), a novel cyclic dodecapeptide containing an unprecedented six five-membered heterocycles. Multiple NMR experiments and MS/MS data were required to assemble its planar structure because of its extensively signal-overlapped NMR spectra. In particular, a 1D HMBC was utilized to orient a three amino acid fragment that could not be placed by standard spectroscopic methods.

Lyngbya majuscula is best recognized for its production of lipopeptides, products of both polyketide synthase (PKS) and nonribosomal polypeptide synthetase (NRPS) biosynthetic origins.1 In fact, natural products of purely amino acid derivation are comparatively rare from this genus. A phytochemical study of a Papua New Guinea collection of this cyanobacterium resulted in the discovery of wewakazole (1), a cyclic peptide integrating structural features uncharacteristic of L. majuscula secondary metabolites. In this paper, we present the isolation and structure determination of this novel marine cyanobacterial metabolite. The L. majuscula strain was collected from a shoreline growth of coral (