Abstract
A didemnin B analog containing a Tic (1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) as a conformationally restrained replacement for tyrosine has been synthesized and shown to have comparable potency as a protein biosynthesis inhibitor. Synthetic highlights include an oxidation of an alcohol to an acid in the presence of the sensitive Tic heterocycle and a modified Schmidt-type one-pot macrocyclization.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Isoquinolines / chemical synthesis*
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Isoquinolines / chemistry
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Isoquinolines / pharmacology*
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Molecular Structure
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Peptides, Cyclic / chemical synthesis*
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Peptides, Cyclic / chemistry
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Peptides, Cyclic / pharmacology*
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Protein Synthesis Inhibitors / chemical synthesis*
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Protein Synthesis Inhibitors / chemistry
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Protein Synthesis Inhibitors / pharmacology*
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Rabbits
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Structure-Activity Relationship
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Tetrahydroisoquinolines*
Substances
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Isoquinolines
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Peptides, Cyclic
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Protein Synthesis Inhibitors
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Tetrahydroisoquinolines
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Tic(5) didemnin B