Revised absolute stereochemistry of natural kulokekahilide-2

Kulokekahilide-2 is a potent cytotoxic depsipeptide isolated from the Hawaiian marine mollusk Philinopsis speciosa. The structure of kutokekahilide-2 was reported to be composed of five amino acids (L-Ala, L-Ile, MeGly, L-MePhe, D-Ala) and two hydroxy acids (D-Hica, 5S,6S,7S-Dtda); however, following its total synthesis, the (1)H NMR spectrum of the synthetic compound was found to be different from that of the natural one, suggesting that the stereochemistry of the reported structure was incorrect. To determine the stereochemistry of the natural compound, arrays of analogues have been prepared using different sets of chiral amino acids, and the absolute stereochemistry of kulokekahilide-2 has been unambiguously confirmed to involve the combination 21-L-Ala, 24-D-MePhe, and 43-D-Ala. (C) 2007 Elsevier Ltd. All rights reserved.