58. Synthesis of Thelepamide via Catalyst-Controlled 1,4-Addition of Cysteine Derivatives, and Structure Revision of Thelepamide
T. Seitz, R. E. Millán, D. Lentz, C. Jiménez, J. Rodríguez, M. Christmann
The first enantioselective total synthesis and structural reassignment of (−)-thelepamide, a cytotoxic tetraketide–amino acid from the marine worm Thelepus crispus, is reported. A convergent approach provides access to all thelepamide diastereomers in six steps from four simple building blocks. Key features of the synthesis include the application of Melchiorre’s organocatalytic thia-Michael reaction and a sonication-assisted assembly of an unprecedented N,O-acetal–hemiacetal moiety. The corrected structure was confirmed by NMR–DFT analysis.