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Ketomethylene Analogues of Phosphoryl Dipeptides Related to Phosphoramidon: Synthesis and Inhibition of Proteases
Author(s) -
GómezMonterrey Isabel,
González Muñiz Rosario,
PérezMartín Concepción,
López de Ceballos María,
Del Río Joaquín,
Teresa GarcíaLópez M.
Publication year - 1992
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19923250503
Subject(s) - phosphoramidon , chemistry , dipeptide , thermolysin , stereochemistry , amide , alkylation , chemical synthesis , ketone , peptide synthesis , peptide bond , enzyme inhibitor , malonate , enzyme , peptide , organic chemistry , biochemistry , trypsin , neprilysin , in vitro , catalysis
Non‐rhamnose‐containing phosphoramidon analogues, in which the amide bond was replaced by the isosteric ketomethylene group, have been synthesized in order to stabilize these compounds to peptidase degradation. The key step in this synthesis was suitable alkylation of a 4‐ketodiester, prepared from Z‐Leu chloromethyl ketone and dimethyl malonate. The ketomethylene dipeptide derivatives P‐Leu Ψ(COCH 2 )( RS )Xaa‐OMe (Xaa = Trp, Phe) are good inhibitors of thermolysin, ACE and specially enkephalinase.