Synthesis of Phakellistatin 11: A Micronesia (Chuuk) Marine Sponge Cyclooctapeptide
| Autor: | Michael D. Williams, Stuart R. Taylor, George R. Pettit, John W. Lippert, Rui Tan |
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| Rok vydání: | 2001 |
| Předmět: |
Stereochemistry
Molecular Conformation Pharmaceutical Science Antineoplastic Agents Cleavage (embryo) Peptides Cyclic Chemical synthesis Analytical Chemistry chemistry.chemical_compound Drug Discovery Tumor Cells Cultured Peptide synthesis Animals Chromatography High Pressure Liquid Pharmacology chemistry.chemical_classification Natural product Molecular Structure biology Organic Chemistry Total synthesis biology.organism_classification Cyclic peptide Porifera Sponge Complementary and alternative medicine chemistry Yield (chemistry) Molecular Medicine |
| Zdroj: | Journal of Natural Products. 64:883-891 |
| ISSN: | 1520-6025 0163-3864 |
| DOI: | 10.1021/np0100441 |
| Popis: | 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-alpha-allyl ester, linear elongation of the octapeptide was performed until the final unit Pro was added. The allyl ester was removed using Pd(0)[P(C(6)H(5))(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. |
| Databáze: | OpenAIRE |
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