270085-21-7Relevant articles and documents
1-Ethyl 2-halopyridinium salts, highly efficient coupling reagents for hindered peptide synthesis both in solution and the solid-phase
Li, Peng,Xu, Jie-Cheng
, p. 8119 - 8131 (2007/10/03)
1-Ethyl-2-halopyridinium salts, BEP, FEP, BEPH and FEPH, were synthesized and proved to be very effective for the synthesis of hindered peptides containing N-methylated or C(α),C(α)-dialkylated amino acid residues. HPLC monitoring of model reactions indicated that these pyridinium salts demonstrated higher reactivities, lower racemization than the commonly used halogenated uronium and phosphonium salts. The efficiency of these pyridinium type coupling reagents was further proved by the synthesis of a series of hindered oligopeptides and active esters with good yields and convenient workup. The 8-11 tetrapeptide fragment of Cyclosporin A (CsA) and the pentapeptide moiety of Dolastatin 15 were also successfully synthesized using these pyridinium salts. The efficiency of these pyridinium type coupling reagents for SPPS was also demonstrated by the solid-phase synthesis of the extremely hindered 8-11 peptide segment of CsA and the linear undecapeptide of CsO. The mechanism of the pyridinium salt mediated coupling reactions was also studied by 1H NMR, IR and HPLC. It was proposed that the major reactive intermediates were the corresponding acyl halide and acyloxypyridinium salts of the N-protected amino acid or peptide. (C) 2000 Elsevier Science Ltd.
Total synthesis of cyclosporin O both in solution and in the solid phase using novel thiazolium-, immonium-, and pyridinium-type coupling reagents: BEMT, BDMP, and BEP
Li, Peng,Xu, Jie Cheng
, p. 2951 - 2958 (2007/10/03)
Cyclosporin O (1), an extensively N-methylated immunosuppressive cyclic undecapeptide isolated from Tolypocladium inflatum Gams, was synthesized in 20-23% overall yield via 4 + 7 segment condensation and cyclization by the combined utilization of novel thiazolium- and immonium-type peptide coupling reagents 2-bromo-3-ethyl-4-methyl thiazolium tetrafluoroborate (BEMT) and 5- (1H-benzotriazol-1-yloxy)-3,4-dihydro-1-methyl 2H-pyrrolium hexachloroantimonate (BDMP) as well as compound 2-bromo-1-ethyl pyridinium tetrafluoroborate (BEP). BEMT and BEP, which have been proven to be very efficient for the coupling of peptide segments containing N-alkylated amino acid residues with respect to the fast reaction speed, low racemization, and high yields, were used to construct hindered amide bonds in CsO with the addition of HOAt, whereas the most efficient HOBt-derived immonium type reagent, BDMP, was used to perform the coupling of coded amino acids in CsO. Thus, the highly hindered protected 8-11 tetrapeptide 25 was successfully synthesized using BEMT in 65% yield, and the 1-7 heptapeptide 21 was obtained in 52-55% yield by the rationally combined utilization of BDMP, BEMT, and BEP. The synthesis of the linear undecapeptide 27 of CsO in the solid phase using BEMT and BEP was accomplished for the further evaluation of the effectiveness of these reagents.
