Total synthesis and proof of relative stereochemistry of (-)-aureonitol

Two trisubstituted epimeric tetrahydrofurans, 1 and 2, have been synthesized in order to confirm the relative stereochemistry in the natural product aureonitol. The key step in the synthesis of 1 and 2 involved a stereoselective intramolecular allylation of an allylsilane with an aldehyde, which introduced the stereotriad in the five-membered ring. The major tetrahydrofuran diastereoisomer 18 from this cyclization reaction was subsequently elaborated to tetrallydrofuran 1. Its 3-epimer (2) was then prepared from 1 via an oxidation - reduction sequence. Compound 1 exhibits identical H-1 NMR data to those reported for aureonitol, which was isolated from Helichrysum aureonitons by Bohlmann in 1979, whereas the H-1 NMR data for 2 are markedly different. The H-1 NMR data (in CDCl3, CD3OD, and C6D6) and C-13 NMR data (in CDCl3) for 1 are also identical with those reported for a natural product isolated from various Chaetomiun sp. by Abraham. Seto, and Teuscher. These findings support Abraham's conclusion that the structure of aureonitol should be revised from 2 to 1. The enantioselective synthesis of 1 has also confirmed that (-)-aureonitol isolated by Abraham contains the (2S,3R,4S) absolute configuration of stereocenters on the tetrahydrofuran ring.