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

Abstract

The first enantioselective total syntheses of (−)-caulamidine D ( 5 ) and (−)-isocaulamidine D ( 6 ) were accomplished. Their absolute configurations were unambiguously elucidated through X-ray crystallography. The isolated natural samples of both 5 and 6 are determined to be the TFA salts instead of the neutral forms. It took 16 steps (longest linear sequence) to divergently access both 5 and 6 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- exo -dig/6- exo -tet amine/nitrile cyclization reaction.