Oligomerization of N,O-Bis(trimethylsilyl)-α-amino Acids into Peptides Mediated by o-Phenylene Phosphorochloridate

Citations Over TimeTop 10% of 1999 papers

Abstract

N,O-Bis(trimethylsilyl)-α-amino acids (N,O-BTMS-AA), mediated by o-phenylene phosphorochloridate (PPC), could oligomerize into polypeptides. The mechanism might go through sequential steps, i.e., the activation of amino acid, the elongation of peptide chain, and the termination of elongation reaction, as can be traced by 31P NMR spectroscopy. The activated amino acid was a five-membered cyclic pentacoordinate phosphoric−carboxylic mixed anhydride. The nucleophilic attack of the amino group of an amino acid or a peptide on the carbonyl group of the intermediate led to the formation of peptide with release of a phosphate ester. The repetition of the reaction sequence generated successively longer N,O-bis(trimethylsilyl)peptides, which were then hydrolyzed to give a series of oligopeptides. It is worth noting that only the N,O-bis(trimethylsilyl)-α-amino acids, not the N,O-bis(trimethylsilyl)-β-amino acids, could be activated and assemble into polypeptides. The mechanism of the five-membered cyclic pentacoordiate phosphoric-amino acid anhydride intermediate showed that phosphorus could choose α-amino acids in the prebiotic synthesis of polypeptides and biosynthesis of proteins.

Related Papers

• → Preparation of Peptide Thioesters using Fmoc-Solid-Phase Peptide Synthesis and its Application to the Construction of a Template-Assembled Synthetic Protein (TASP)(1997)116 cited
• → Synthesis of peptide thioesters via an N–S acyl shift reaction under mild acidic conditions on an N‐4,5‐dimethoxy‐2‐mercaptobenzyl auxiliary group(2009)34 cited
• → N-to-C Solid-Phase Peptide and Peptide Trifluoromethylketone Synthesis Using Amino Acid tert-Butyl Esters.(2002)16 cited
• → Preparation of Peptide Thioesters through Fmoc‐Based Solid‐Phase Peptide Synthesis by Using Amino Thioesters(2013)9 cited
• → A New Strategy for Inverse Solid-Phase Peptide Synthesis(2001)1 cited