RSC Advances p. 30720 - 30728 (2019)
Update date:2022-08-17
Topics:
Goldschmidt G?z, Viktória
Nagy, Adrienn
Farkas, Viktor
Keszei, Ern?
Perczel, András
Nowadays, in Solid Phase Peptide Synthesis (SPPS), being either manual, automated, continuous flow or microwave-assisted, the reaction with various coupling reagents takes place via in situ active ester formation. In this study, the formation and stability of these key active esters were investigated with time-resolved 1H NMR by using the common PyBOP/DIEA and HOBt/DIC coupling reagents for both α- and β-amino acids. Parallel to the amide bond formation, the hydrolysis of the α/β-active esters, a side reaction that is a considerable efficacy limiting factor, was studied. Based on the chemical nature/constitution of the active esters, three amino acid categories were determined: (i) the rapidly hydrolyzing ones (t < 6 h) with smaller (Ala) or even longer side chains (Arg) holding a large protecting group; (ii) branched amino acids (Ile, Thr) with slowly hydrolyzing (6 < t < 24 h) propensities, and (iii) non-hydrolyzing ones, such as the hard-to-couple β-amino acids or β-sugar amino acid derivatives, stable for longer times (t > 24 h) in solution. The current insight into the kinetics of this key hydrolysis side reaction serves as a guide to optimize the coupling conditions of α- and β-amino acids, thereby saving time and minimizing the amounts of reagents and amino acids to be used-all key factors of more environmentally friendly chemistry.
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Doi:10.1021/acs.joc.6b02329
(2016)Doi:10.1007/s10593-013-1254-9
(2013)Doi:10.1002/hlca.200900141
(2009)Doi:10.1007/s10562-013-0976-8
(2013)Doi:10.1016/j.apcata.2014.08.027
(2014)Doi:10.1021/jo01295a047
(1980)