Total Syntheses of Conformationally Constrained Didemnin B Analogues. Replacements ofN,O-Dimethyltyrosine with l -1,2,3,4-Tetrahydroisoquinoline and l -1,2,3,4-Tetrahydro-7-methoxyisoquinoline

The design and synthesis of two conformationally constrained analogues of didemnin B are described. The [N,O-Me(2)Tyr(5)]residue of didemnin B was replaced with L-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) and L-1,2,3,4-tetrahydro-7-methoxyisoquinoline-3-carboxylic acid (MeO-Tic), which mimic the N,O-dimethylated tyrosine while constraining the conformation of the molecule. Preliminary results indicate that the conformation of the [N,O-Me(2)Tyr(5)]residue closely matches the conformation imposed by the Tic replacement.