Modifying a peptide coupling reaction leads to a much easier work-up

30 September 2005

Workers at Johnson and Johnson have recently described the synthesis of Gastrazole (JB5008) and the penultimate step of the synthesis was the peptide coupling shown below:

Initially standard peptide coupling reagents were used — 1-hydroxybenzotriazole, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) and 4-dimethylaminopyridine (DMAP) — and this gave the product in good yield (75%) and purity (96% chemical purity, 99.7% optical purity). However the work up which entailed precipitating the product with water gave a very sticky solid that was difficult to filter and would lead to problems on larger scale.

Using EDC alone as the coupling agent avoided this problem and gave a filterable solid without any yield or purity penalties.

D. Ormerod, B. Willemsens et al, Org. Proc. Res. Dev., 2005, 9, 499-507.