Synthesis of the dolastatin 3 isomer cyclo-[L-Pro-L-Leu-L-Val-(R,S)-(gln)Thz-(gly)Thz]

George Pettit, Cedric W. Holzapfel

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

With application of mixed carbonic anhydride and dicyclohexylcarbodiimide-N-hydroxysuccinimide peptide bond forming methods culminating in a 2,4,5-trichlorophenol active ester promoted cyclization reaction, synthesis (cf., Scheme I) of cyclo-[L-Pro-L-Leu-L-Val-(R,S)-(gln)Thz-(gly)Thz] was completed. Comparison of this cyclic peptide with the Indian Ocean sea hare cell growth inhibitory constituent dolastatin 3 clearly showed that the natural peptide possesses a closely related structure. The high resolution (400 MHz) 1H NMR and 13C NMR spectra of the synthetic peptides were evaluated in detail and suggested that dolastatin 3 may contain (R)-(gln)Thz and/or a modified Pro-Leu-Val sequence.

Original languageEnglish (US)
Pages (from-to)4580-4585
Number of pages6
JournalJournal of Organic Chemistry
Volume51
Issue number24
StatePublished - 1986

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Isomers
Peptides
Nuclear magnetic resonance
Dicyclohexylcarbodiimide
Cyclic Peptides
Cyclization
Cell growth
Carbon Dioxide
Esters
dolastatin 3
2,4,5-trichlorophenol
N-hydroxysuccinimide

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

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

In: Journal of Organic Chemistry, Vol. 51, No. 24, 1986, p. 4580-4585.

Research output: Contribution to journalArticle

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abstract = "With application of mixed carbonic anhydride and dicyclohexylcarbodiimide-N-hydroxysuccinimide peptide bond forming methods culminating in a 2,4,5-trichlorophenol active ester promoted cyclization reaction, synthesis (cf., Scheme I) of cyclo-[L-Pro-L-Leu-L-Val-(R,S)-(gln)Thz-(gly)Thz] was completed. Comparison of this cyclic peptide with the Indian Ocean sea hare cell growth inhibitory constituent dolastatin 3 clearly showed that the natural peptide possesses a closely related structure. The high resolution (400 MHz) 1H NMR and 13C NMR spectra of the synthetic peptides were evaluated in detail and suggested that dolastatin 3 may contain (R)-(gln)Thz and/or a modified Pro-Leu-Val sequence.",
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