SYNTHESIS OF TUCKOLIDE, A NEW CHOLESTEROL-BIOSYNTHESIS INHIBITOR

Tuckolide (decarestrictine D), a 10-membered lactone isolated from P. corylophilum and polyporus tuberaster fungi that potently inhibits cho lesterol biosynthesis, was synthesized, The key steps include a Sharpl ess catalytic asymmetric dihydroxylation reaction (AD) of the methoxym ethyl (MOM) ether protected diene 2 and a direct Corey-Nicolaou lacton ization reaction of seco-acid 1 with added silver perchlorate. The sel ectivity of the dihydroxylation step was found to be highly dependent on the nature of the protecting group adjacent to the diene in 2. The selectivity of the asymmetric dihydroxylation reaction of 2 indicates that both steric and electronic effects can lead to significant amount s of the undesired isomers. This synthesis establishes the absolute st ereochemistry of tuckolide showing the C3 hydroxyl bearing carbon with an S-configuration comparable in an absolute sense to that in the lac tone portion of the HMG-CoA reductase inhibitor compactin.