T. Lister, M. Perkins
Aug 30, 2004
Citations
0
Influential Citations
12
Citations
Journal
Australian Journal of Chemistry
Abstract
A highly stereocontrolled synthesis of (2S,3R,5R,6S)-6-[(1E,3R)-1,3-dimethylhex-1-enyl]-2-ethyl-2-hydroxy-3,5-dimethyltetrahydro-4H-pyran-4-one has been achieved in 13 steps and an overall yield of 7.6% from (R)-(+)-4-benzyloxazolidin-2-one. This substrate-controlled asymmetric synthesis utilized Paterson’s lactate-derived chiral ketone (2S)-2-(benzoyloxy) pentan-3-one to generate the 5R and 6S stereocentres and alkylation of an Evans’ auxiliary to generate the remote side-chain 3R stereocentre. Furthermore, a novel, highly efficient, and selective strategy was used to generate an enol trimethylsilyl ether whose subsequent Mukaiyama aldol condensation gave the acyclic precursor to the final product. A thermodynamically controlled cyclization then gave (2S,3R,5R,6S)-6-[(1E,3R)-1,3-dimethylhex-1-enyl]-2-ethyl-2-hydroxy-3,5-dimethyltetrahydro-4H-pyran-4-one with control of the 2S and 3R stereocentres. The NMR spectroscopic data and optical rotation obtained for synthetic (2S,3R,5R,6S)-6-[(1E,3R)-1,3-dimethylhex-1-enyl]-2-ethyl-2-hydroxy-3,5-dimethyltetrahydro-4H-pyran-4-one were consistent with those reported for the hemiacetal isolated from Siphonaria australis, and thus, prove the absolute and relative configuration of the natural product.