Enantioselective Total Syntheses of (-)-Caulamidine D and (-)-Isocaulamidine D and Their Absolute Configuration Reassignment.

The first enantioselective total syntheses of (-)-caulamidine D () and (-)-isocaulamidine D () were accomplished. Their absolute configurations were unambiguously elucidated through X-ray crystallography. The isolated natural samples of both and are determined to be the TFA salts instead of the neutral forms. It took 16 steps (longest linear sequence) to divergently access both and following a unified strategy. The key reactions include (1) development and application of an asymmetric Meerwein-Eschenmoser-Claisen rearrangement to construct the challenging C10, C23 consecutive stereocenters and (2) application of a cascade 6--dig/6--tet amine/nitrile cyclization reaction.