Enzymatic synthesis of beta-lactam antibiotics via direct condensation.

Abstract:

:In this paper, the feasibility of precipitation driven synthesis of acidic and zwitterionic beta-lactam antibiotics is studied. As an example of the first type, penicillin G was produced in good yield (160 mmol kg(-1)) directly from the free acid and amine aqueous substrate suspension, where the synthesis product precipitated. Such a precipitation driven synthesis via direct reversal of the hydrolytic reaction is thermodynamically unfavourable for zwitterionic beta-lactam antibiotics, such as amoxicillin. In this paper, a novel method is suggested to help favour precipitation of (poorly soluble) product salts by deliberate addition of certain counter-ions. After screening a number of different counter-ions, it was found that the amoxicillin anion forms a poorly soluble salt with Zn(2+). Despite increased beta-lactam degradation due to the presence of zinc ions, in a synthetic reaction with 0.1 M ZnSO(4) present the synthetic yield could be increased at least 30-fold.

journal_name

J Biotechnol

journal_title

Journal of biotechnology

authors

Ulijn RV,De Martin L,Halling PJ,Moore BD,Janssen AE

doi

10.1016/s0168-1656(02)00211-0

subject

Has Abstract

pub_date

2002-11-13 00:00:00

pages

215-22

issue

3

eissn

0168-1656

issn

1873-4863

pii

S0168165602002110

journal_volume

99

pub_type

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