Synthesis of p-hydroxyubenimex.
p-Hydroxyubenimex, (2S,3R)-3-amino-2-hydroxy-4-p-hydroxyphenylbutyryl-L-leucine, was synthesized starting from D-tyrosine. The structure and stereochemistry of the synthesized product were confirmed by comparison with p-hydroxyubenimex that was chemically transformed from ubenimex, an aminopeptidase inhibitor of microbial origin. Compared to ubenimex, p-hydroxyubenimex is more active against aminopeptidase B but less active against leucine aminopeptidase. By using the synthetic p-hydroxyubenimex as a reference sample, one of the metabolites of ubenimex was identified as p-hydroxyubenimex. The (2R,3R)-stereoisomer of p-hydroxyubenimex was also prepared. However, its activity against aminopeptidases was much weaker.
Saino
T
T
Research Laboratories, Nippon Kayaku Co., Ltd., Tokyo, Japan.
Seya
K
K
Nishizawa
R
R
Takita
T
T
Aoyagi
T
T
Umezawa
H
H
D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D006900:Hydroxylation; D007930:Leucine / Q000031:analogs & derivatives*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014443:Tyrosine
D000900:Anti-Bacterial Agents; D014443:Tyrosine; D000626:Aminopeptidases; D007930:Leucine; C012211:ubenimex