Key analogs of the tetrapeptide subunit of RA-VII and deoxybouvardin
1Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037, USA.
Abstract:
The synthesis and evaluation of two key analogs 3 and 4 of the potent antitumor antibiotics deoxybouvardin (1) and RA-VII (2) which contain fundamental modifications in the tetrapeptide subunit are described. Unlike the natural products, these agents 3 and 4, which substitute (Gly)4 and (Gly)3 for the D-Ala-Ala-NMe-Tyr(OMe)-Ala tetrapeptide subunit, adopt conformations in which the central amide in the cycloisodityrosine subunit adopts its inherently preferred trans stereochemistry and both were found to be biologically inactive.
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