Total Synthesis of Brasilicardin A.

This study reports a practical synthetic method for brasilicardin A, a diterpene natural product with potent immunosuppressive effects, possessing an unusual trans-syn-trans perhydrophenanthrene skeleton. The key reactions include a diastereoselective Eschenmoser-Claisen rearrangement, a highly diastereoselective alkylation of a decalin nitrile, and a Me2CuLi-mediated intramolecular Michael addition reaction to construct the strained, functionalized trans-syn-trans perhydrophenanthrene skeleton. In addition, an optimized protecting-group strategy was employed to reduce the need for subsequent deprotection steps and enhance reaction efficiency.