Applications of BOP reagent in solid phase synthesis

Abstract

Using a variety of activating agents, a kinetic study was carried out to evaluate the rate of solid phase side‐chain to side‐chain cyclization of Asp 3 to Lys 12 in the model peptide‐resin, [Ala 15 ]‐GRF(1–29)‐BHA‐resin. Asp 3 and Lys 12 were introduced in the peptide chain by using N α ‐Boc amino acids in conjunction with the OFm/Fmoc side‐chain protection scheme. The OFm and Fmoc side‐chain protecting groups were shown to be stable to diisopropylethylamine and selectively deprotected on treatment with 20% piperidine in DMF. Solid phase side‐chain to side‐chain cyclization (lactamization) was shown to proceed to completion within 2 h using benzotriazol‐1‐yl‐oxy‐tris(dimethylamino)‐phosphonium hexafluorophosphate (BOP reagent) while the reaction was only 55% completed in 24h using DCC/HOBt. Solid phase side‐chain to side‐chain cyclization by the BOP procedure not only proceeded more rapidly but also gave a purer cyclic product.