Design and synthesis of peptidomimetics containing the -CHFS- moiety.
Published: 2006
Language: eng
Number of pages: 100
ISBN-13: 9780494213575
Description: Proteases have become drug targets in the treatment of disease conditions linked to their aberrant over- or under-expression. For serine proteases, although numerous potent irreversible and reversible inhibitors have been developed, the area of transition-state analogues with isosteres of tetrahedral geometry has been explored less frequently. Fluorinated peptide analogues containing a tetrahedral alpha-fluoroarylthioether functionality that were designed and synthesized as inhibitors of alpha-chymotrypsin displayed limited stability in aqueous media, and were obtained as inseparable diastereomeric mixtures. Here, the synthesis of more stable compounds containing strongly electron-withdrawing thiophenyl groups is outlined. The overall yields of the compounds were improved by the discovery and application of an  in-situ DAST fluorination of thiohemiacetals obtained via the corresponding aldehydes. Compounds containing para trifluoromethylthiophenyl displayed improved aqueous stability and afforded a separation of the diastereomers.
Notes: Source: Masters Abstracts International, Volume: 45-03, page: 1504.

Thesis (M.Sc.)--University of Toronto, 2006.

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