title: Ketomethylenebestatin: synthesis and aminopeptidase inhibition.
abstract: The synthesis of (6R,5S,2RS)-6-amino-5-hydroxy-2-isobutyl-4-oxo-7- phenylheptanoic acid (9), a carbaanalogue of the aminopeptidase (AP) inhibitor bestatin (1) is described. This synthesis was carried out by a malonic ester alkylation with the suitably protected halomethyl ketone of (2S,3R)-AHPBA*), followed by a second alkylation with isobutyl bromide of the resulting 4-ketodiester, and subsequent decarboxylation and deprotection. The inhibitory potencies of the 1:1 diastereomeric mixture 9 against AP-B, AP-M and Leu-AP were approximately 10-fold lower than those of bestatin.
authors.affiliation: Instituto de Química Médica, Juan de la Cierva, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Herranz
authors.forename: J
authors.initials: J
authors.lastname: Castro-Pichel
authors.forename: M T
authors.initials: MT
authors.lastname: García-López
authors.forename: I
authors.initials: I
authors.lastname: Gómez-Monterrey
authors.forename: C
authors.initials: C
authors.lastname: Pérez
authors.forename: S
authors.initials: S
authors.lastname: Vinuesa
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000818:Animals; D006538:Heptanoic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D013552:Swine
chemical_list: D006538:Heptanoic Acids; C082772:ketomethylenebestatin; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex