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

17 Citations (Scopus)

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
StatePublished - 1985

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Isomers
Thiazoles
Peptides
Amino Acids
Cyclic Peptides
Cyclization
Heterojunction bipolar transistors
Cell growth
Carbon Dioxide
Spectrum analysis
Esters
dolastatin 3
2,4,5-trichlorophenol

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Synthesis of the cyclo-(gly)Thz-(R)- and cyclo-[(gly)Thz-(S)-(gln)Thz-L-Val-L-Leu-L-Pro] isomers of dolastatin 3. / Pettit, George; Nelson, Paul S.; Holzapfel, Cedric W.

In: Journal of Organic Chemistry, Vol. 50, No. 15, 1985, p. 2654-2659.

Research output: Contribution to journalArticle

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