In this paper, the feasibility of precipitation driven synthesis of acidic and zwitterionic -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 -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 Zn2 . Despite increased -lactam degradation due to the presence of zinc ions, in a synthetic reaction with 0.1 M ZnSO4 present the synthetic yield could be increased at least 30-fold.