Total synthesis of myceliothermophins A-E

Total synthesis of an antitumor compound myceliothermophin A and related compounds based on a convergent synthetic strategy was investigated. A common decalin skeleton of myceliothermophins was stereoselectively constructed by an IMDA reaction. The fully elaborated precursor of myceliothermophins was obtained via aldol reaction of N-protected gamma-methoxylactam with decalin aldehyde. By using Teoc group for the protection of nitrogen atom of lactam ring, selective deprotection prior to the hydrolysis of methoxyaminal moiety was successfully achieved to obtain gamma-methoxylactams (myceliothermophins C and D). Subsequent hydrolysis of these compounds afforded the corresponding gamma-hydroxylactam, and myceliothermophins A and B in high yield. Myceliothermophin E was also synthesized by dehydration of the obtained gamma-hydroxylactams. The absolute configurations of myceliothermophins A-E were also successfully determined. (C) 2012 Elsevier Ltd. All rights reserved.