Enzymatic synthesis of beta-lactam antibiotics via direct condensation.
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.
Ulijn
R V
RV
Department of Pure and Applied Chemistry, Thomas Graham Building, 295 Cathedral Street, G1 1XL Glasgow, Scotland, UK. rein.ulijn@ed.ac.uk
De Martin
L
L
Halling
P J
PJ
Moore
B D
BD
Janssen
A E M
AE
D000658:Amoxicillin / Q000138:chemical synthesis / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000378:metabolism; D002384:Catalysis; D011232:Chemical Precipitation; D004789:Enzyme Activation; D004795:Enzyme Stability; D004926:Escherichia coli / Q000201:enzymology*; D005240:Feasibility Studies; D010399:Penicillin Amidase / Q000096:biosynthesis* / Q000737:chemistry*; D010400:Penicillin G / Q000138:chemical synthesis / Q000378:metabolism; D011786:Quality Control
D000900:Anti-Bacterial Agents; D000658:Amoxicillin; D010399:Penicillin Amidase; D010400:Penicillin G