Document Detail

Synthesis and structure determination of kahalalide F (1,2).
MedLine Citation:
PMID:  11707116     Owner:  NLM     Status:  MEDLINE    
Kahalalide F, the only member of the family of peptides called kahalalides, isolated from the sacoglossan mollusc Elysia rufescens and the green alga Bryopsis sp., with important bioactivity, is in clinical trials for treatment of prostate cancer. An efficient solid-phase synthetic approach is reported. Kahalalide F presents several synthetic difficulties: (i) an ester bond between two beta-branched and sterically hindered amino acids; (ii) a didehydroamino acid; and (iii) a rather hydrophobic sequence with two fragments containing several beta-branched amino acids in a row, one of them terminated with a saturated aliphatic acid. The cornerstones of our strategy were (i) a quasiorthogonal protecting system with allyl, tert-butyl, fluorenyl, and trityl-based groups, (ii) azabenzotriazole coupling reagents, (iii) formation of the didehydroamino acid residue on the solid phase, and (iv) cyclization and final purification in solution. HPLC, high-field NMR, and biological activity studies showed that the correct stereochemistry of the natural product is that proposed by Rinehart et al. whereas the stereochemistry proposed by Scheuer et al. is that of a biologically less active diastereoisomer.
A López-Macià; J C Jiménez; M Royo; E Giralt; F Albericio
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  123     ISSN:  0002-7863     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-14     Completed Date:  2002-01-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  11398-401     Citation Subset:  IM    
Department of Organic Chemistry, University of Barcelona, 08028 Barcelona, Spain.
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MeSH Terms
Algae, Green / chemistry
Amino Acid Sequence
Antineoplastic Agents / chemical synthesis*,  chemistry
Chromatography, High Pressure Liquid
Mollusca / chemistry
Nuclear Magnetic Resonance, Biomolecular
Peptides / chemical synthesis*,  chemistry
Protein Conformation
Reg. No./Substance:
0/Antineoplastic Agents; 0/Depsipeptides; 0/Peptides; 149204-42-2/kahalalide F

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