Collect. Czech. Chem. Commun. 1994, 59, 691-706

A Comparative Study of BOP as a Coupling Agent Using Simultaneous Multiple Peptide Synthesis

Jan Ježeka and Richard A. Houghtenb

a Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic
b Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, U.S.A.


A parallel simultaneous synthesis of multiple peptides was carried out in which the coupling agents BOP and DIPCI were compared. For peptides lacking Asn, no differences in average yield or RP HPLC purity were found. For peptides having Asn in their sequences, however, the yield and purity were significantly lower for BOP when compared to DIPCI. The addition of HOBt to BOP mediated couplings did not lead to improved results. In fact, BOP condensations without HOBt gave, on average, slightly purer peptides. Comparing the results for peptides prepared with BOP dissolved in DMF, NMP, or NMP + 20% DMSO, NMP afforded the best and DMF the worst results, but the differences were not significant. Peptides prepared using BOP, combined with in situ neutralization, were obtained both in higher yield and purity when compared with classical neutralization. In all BOP mediated couplings, peptides with Asn were obtained in lower yield and purity than peptides without Asn. FAB MS and amino acid analysis revealed that the side products are peptides with deleted Asn.