Total syntheses of conformationally constrained didemnin B analogues. replacements of N,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.
Tarver
J E
JE
Department of Chemistry, University of Pennsylvania, Philadelphia, PA 19104-6323, USA.
Pfizenmayer
A J
AJ
Joullié
M M
MM
D047630:Depsipeptides; D004354:Drug Screening Assays, Antitumor; D006131:Growth Inhibitors / Q000138:chemical synthesis; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D011487:Protein Conformation; D044005:Tetrahydroisoquinolines; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
C444259:1,2,3,4-tetrahydro-7-methoxyisoquinoline-3-carboxylic acid; D047630:Depsipeptides; D006131:Growth Inhibitors; D007546:Isoquinolines; D010456:Peptides, Cyclic; D044005:Tetrahydroisoquinolines; D014443:Tyrosine; C030051:didemnins; C014843:1,2,3,4-tetrahydroisoquinoline