Potential inhibitors of L-asparagine biosynthesis. 2. Chemistry and biological activity of beta-hydroxyaspartic acid and its derivatives.

Abstract:

:Several derivatives of erythro-beta-hydroxy-DL-aspartic acid (1) were prepared as a potential inhibitors of L-asparagine synthetase (ASase) from rat Novikoff hepatoma. Benzylation of 1 gave the dibenzyl ester 2 which upon coupling with carbobenzoxyglycine afforded the blocked dipeptide 3. Deblocking of 3 gave glycl-erythro-beta-hydroxyl-DL-aspartic acid (4) which could not be diazotized. The dimethyl ester of 1 was coupled with carbobenzoxyglycine to give the blocked dipeptide 7a which was deblocked to give dimethyl glycel-erythro-beta-hydroxy-DL-aspartate hydrochloride (8). Diazotization of 8 gave impure diazo compound 9 which on reaction with HCl gave the chloro compound 10. The methods of isolation, assay, and inhibition of ASase are discribed. At 10 mM concentrations 10, 1, and its D and L enantiomers inhibit ASase by 45, 47, 36 and 66 percent, respectively.

journal_name

J Med Chem

authors

Mokotoff M,Bagaglio JF,Parikh BS

doi

10.1021/jm00238a006

keywords:

subject

Has Abstract

pub_date

1975-04-01 00:00:00

pages

354-8

issue

4

eissn

0022-2623

issn

1520-4804

journal_volume

18

pub_type

杂志文章