Controlled peptide synthesis - using alpha aminoacid ester(s) with transition metal complexes, useful as single pot reaction

摘要

Peptide synthesis with alpha-amine acid esters with transition metal complex comprises (a) formation of L-M(hal)m+l-,As2Z(H)l complex from (L-M(hal)m)2AS2ZH in water-free solvent, opt. in the presence of base; (b) formation of L-M(hal)m-1AS2-AS1Z complex by addn. of AS2OR2, in the presence of base where none is used in step (a); (c) repetition of step (b) with aminoacid ester (which may be the same as used in previous step) to lengthen the N-terminal end of the peptide chain on the complex; (d) acidification of the soln. to cleave the M-peptide complex; and (e) sepn. of the peptide from the reaction mixt.. Pref. in complex ZH+(ASN)nNHR1 or (ASN)nOR2; R1 = H or organic gp. (esp. 1-4C alkyl); R2 = organic gp. (esp. 1-4C alkyl or benzyl); m = transition metal, esp. Rh, Ir, Pd, Mo, Ru, Co, Ni or Pt; l = ligand, esp. CO, NO, trialkylphosphine, triarylphosphine, Me2NCH2C6H4, C2H4, cycloctene, allyl, cycloctadiene, cyclopentadienyl, pentamethyl cyclopentadienyl (cp asterisk) benzene or hexanethylbenzene; hal = halo esp. Cl or Br; ASN = alpha aminoacid (esp. glycine, alanine, serine, leucine, or aspartate ester) whose C-terminal end has ester or amide function; ASN-ASN = peptide linkage between 2 aminoacids, whose C-terminal end is on the right; L = 0 or 1; m = 1 or 2; n = 0 or natural number; N = natural number. USE/ADVANTAGE - The process is useful in peptide synthesis. It allows controlled synthesis and may be as single-pot reaction or with isolation of the intermediates.gt