Synthesis of phakellistatin 11: A Micronesia (Chuuk) marine sponge cyclooctapeptide

George Pettit, J. W. Lippert, S. R. Taylor, R. Tan, M. D. Williams

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The cyclic octapeptide phakellistatin 11 (1), a constituent of The Federated States of Micronesia (Chuuk) marine sponge Phakellia sp., was synthesized using solid-phase techniques. An initial solution-phase synthesis proved to be inadequate owing to spontaneous deprotection of the Fmoc group at the heptapeptide stage. Using the PAL resin attachment and proceeding from Fmoc-Glu-α-allyl ester, linear elongation of the octapeptide was performed until the final unit Pro was added. The allyl ester was removed using Pd0[P(C6H5)3]4. Cleavage of the final Fmoc group and cyclization with PyAOP provided phakellistatin 11 (1) in 17% overall yield. The synthetic specimen of phakellistatin 11 (1) was found to be chemically but not biologically (cancer cell lines) identical to the natural product. The result suggested a conformational difference or more likely the presence of a trace amount of a highly active antineoplastic agent that binds noncovalently to the natural cyclic octapeptide 1.

Original languageEnglish (US)
Pages (from-to)883-891
Number of pages9
JournalJournal of Natural Products
Volume64
Issue number7
DOIs
StatePublished - 2001

Fingerprint

Chuuk
Micronesia
Porifera
Federated States of Micronesia
esters
synthesis
antineoplastic agents
Esters
resins
Cyclization
cell lines
Biological Products
Antineoplastic Agents
Elongation
Resins
Cells
Cell Line
phakellistatin 1
phakellistatin 11
Neoplasms

ASJC Scopus subject areas

  • Plant Science
  • Chemistry (miscellaneous)
  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Synthesis of phakellistatin 11 : A Micronesia (Chuuk) marine sponge cyclooctapeptide. / Pettit, George; Lippert, J. W.; Taylor, S. R.; Tan, R.; Williams, M. D.

In: Journal of Natural Products, Vol. 64, No. 7, 2001, p. 883-891.

Research output: Contribution to journalArticle

Pettit, George ; Lippert, J. W. ; Taylor, S. R. ; Tan, R. ; Williams, M. D. / Synthesis of phakellistatin 11 : A Micronesia (Chuuk) marine sponge cyclooctapeptide. In: Journal of Natural Products. 2001 ; Vol. 64, No. 7. pp. 883-891.
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