Synthesis of the cyclo-[(gly)Thz-(R)-and cyclo-[(gly)Thz-(S)-(gln)Thz-L-Val-L-Leu-L-Pro] Isomers of Dolastatin 3

George Pettit, Paul S. Nelson, Cedric W. Holzapfel

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

An all-L configuration reverse order of peptide bonding possibility for the cell growth inhibitory (PS system) cyclic peptide dolastatin 3 was eliminated by synthesis of thiazole amino acid containing peptide 2. By employing a series (Scheme I) of mixed carbonic anhydride (except for 9 →11 where DCCI-HBT was used) peptide bond forming reactions with N-Boc protection and a 2,4,5-trichlorophenol active ester cyclization step, cyclic pentapeptide 2 was obtained as a mixture of diastereomers corresponding to the (R)- and (S)-(gln)Thz unit. The thiazole amino acid components were synthesized employing a Hantzsch reaction as the key step (cf. Scheme II). Spectral analysis of the individual (R)- and (S)-(gln)Thz cyclic pentapeptide 2 removed both as structural candidates for dolastatin 3.

Original languageEnglish (US)
Pages (from-to)2654-2659
Number of pages6
JournalJournal of Organic Chemistry
Volume50
Issue number15
DOIs
StatePublished - Jul 1985

ASJC Scopus subject areas

  • Organic Chemistry

Fingerprint Dive into the research topics of 'Synthesis of the cyclo-[(gly)Thz-(R)-and cyclo-[(gly)Thz-(S)-(gln)Thz-<sub>L</sub>-Val-<sub>L</sub>-Leu-<sub>L</sub>-Pro] Isomers of Dolastatin 3'. Together they form a unique fingerprint.

  • Cite this