Optically active N- and C-terminal building blocks for the synthesis of peptidyl olefin peptidomimetics

Sima Mirilashvili, Naama Chasid-Rubinstein, Amnon Albeck

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Peptidyl olefin peptidomimetics serve as biologically active compounds or as intermediates for other peptidyl isosteres. The N-terminal side of the C=C bond could be easily prepared in an optically pure form from α-amino acids. Synthesis of C-terminal building blocks in an optically pure form is more challenging. We developed a chemoenzymatic stereoselective approach to such optically active C-terminal building blocks to be assembled into peptidyl olefins by a variety of reactions. They include an electrophilic aldehyde and nucleophilic sulfone, phosphonium salt, phosphonate, and diselenide. Key enzymatic hydrolysis of prochiral diesters to the corresponding hydroxy esters introduces optical activity. The sequence of the subsequent chemical reactions, either protection- hydrolysis-functionalization or functionalization-hydrolysis- protection, determines the absolute stereochemistry of the final building blocks.

Original languageEnglish
Pages (from-to)4671-4686
Number of pages16
JournalEuropean Journal of Organic Chemistry
Issue number24
DOIs
StatePublished - Aug 2010

Keywords

  • Asymmetric synthesis
  • Enzymes
  • Olefination
  • Peptidomimetics
  • Stereocontrol

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