“…However, Gerlt et al (35,36) have pointed out that proton transfer to carbonyl oxygen can be assisted by weak acids if the pKa of the resultant enol is close to that of the general acid and if the proton transfer is late in the transition state. We do not know the pKa of enol intermediate 2, but based on the most appropriate models available, we estimate it to be at least 12 (37). Thus, in this context, the asparagine amide group (pKa 15.1, estimated from acetamide) (38,39) and water (pKa = 15.7) could serve as electrophilic catalysts and in stabilization of the negatively charged 0-4 of the intermediates.…”