Total synthesis of (±)-luminacin D

A 15-step synthesis of (+/-)-luminacin D from ethyl pent-2-ynoate is reported. The pivotal step involves the formation of the central C-2'/C-3' bond of the natural product by condensation of the titanium enolate derived from aromatic ketone 1 with aldehyde 2a. A remote asymmetric centre in aldehyde 2a exerts control over the stereochemical course of this reaction, with the major adduct (3a, 54% yield) possessing the required (2'S*,3'R*,5R*)-stereochemistry. This assignment was unambiguously established by X-ray crystallography of late stage synthetic intermediate, 17. Further manipulation of 3a (six steps) yielded synthetic ()-luminacin D spectroscopically identical to material isolated from Streptomyces sp. Mer-VD1207 by Naruse et al. (C) 2007 Elsevier Ltd. All rights reserved