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Synthesis and biological activity of substituted [[3(S)-(acylamino)-2-oxo-1-azetidinyl]oxy]acetic acids. A new class of heteroatom-activated beta-lactam antibiotics.

Abstract：

:The synthesis of substituted [[3(S)-(acylamino)-2-oxo-1-azetidinyl]oxy]acetic acids (1) is described. 3-[(Carbobenzyloxy)amino]-N-hydroxy-2-azetidinones (13a,b), prepared from serine and threonine, were alkylated with 2-(trimethylsilyl)ethyl bromoacetate in the presence of potassium carbonate in THF/H2O. Alkylation with secondary alpha-bromo esters was accomplished with potassium hydroxide in dimethyl sulfoxide. The Cbz group was replaced with the 2-(2-amino-4-thiazolyl)-2(Z)-(methoxyimino)acetamido side chain by catalytic hydrogenation followed by treatment with 21. Removal of the 2-(trimethylsilyl)ethyl ester with fluoride ion provided derivatives suitable for antimicrobial evaluation. In vitro tests showed that the title compounds possess significant activity predominantly against Gram-negative bacteria.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Woulfe SR,Miller MJ

doi

10.1021/jm00148a013

subject

Has Abstract

pub_date

1985-10-01 00:00:00

pages

1447-53

issue

10

eissn

0022-2623

issn

1520-4804

journal_volume

28

pub_type

杂志文章

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