Tandem deprotection/coupling for peptide synthesis in water at room temperature

Abstract

A tandem deprotection/coupling sequence is reported for solution-phase peptide synthesis in water under micellar catalysis conditions using the designer surfactant TPGS-750-M.

The Hydrophobic Effect Applied to Organic Synthesis: Recent Synthetic Chemistry “in Water”

“…There are also many "firsts" in micellar catalysis appliedt oo rganic synthesis, such as:1 )new ligands designed for applications based on micellar catalysis in water; [17,19,23,38] 2) ppm level metal-catalyzed processes; [27,39,50,54,56] 3) new heterogeneous nanoparticles that catalyze av ariety of important, commonly utilized reactions; [27,39,49,50] 4) new hybrid micellar derivatives that incorporate reagents within their structure; [25,49,67,69] 5) industrially important developments on the use of micelles influenced by the presenceo fc o-solvents; [75][76][77][78] and 6) examples of one-pot tandem processes enabled by micellar conditions. [27,81,82,85,88,89] These and several relatede xamples from just the past few years further documentt he potentialo ft his blossoming technology,i llustrating new synthetic chemistry that is sustainable, environmentally responsible, and acknowledges that chemistry as practiced today must be changedt ob ei ns tep with the laws of Nature. The contributions described herein are part of the process of helping us to betteru nderstand the "new rules" under whichchemistry will be operating going forward.…”

“…These and several other fascinating and intriguing discoveries, as details associated with the various topics in this review, are presented herein. There are also many “firsts” in micellar catalysis applied to organic synthesis, such as: 1) new ligands designed for applications based on micellar catalysis in water; 2) ppm level metal‐catalyzed processes; 3) new heterogeneous nanoparticles that catalyze a variety of important, commonly utilized reactions; 4) new hybrid micellar derivatives that incorporate reagents within their structure; 5) industrially important developments on the use of micelles influenced by the presence of co‐solvents; and 6) examples of one‐pot tandem processes enabled by micellar conditions . These and several related examples from just the past few years further document the potential of this blossoming technology, illustrating new synthetic chemistry that is sustainable, environmentally responsible, and acknowledges that chemistry as practiced today must be changed to be in step with the laws of Nature.…”

“…Using this convergent approach, the acyclic precursor to gramicidin S, a decapeptide antibiotic, was readily prepared based on both a “5+5” and “8+2” approach. No racemization was detected in either the coupling or tandem deprotection/coupling steps (Scheme ) …”

“…Using this convergent approach, the acyclic precursor to gramicidin S, ad ecapeptidea ntibiotic, was readily prepared based on both a" 5+ 5" and" 8+ 2" ap-proach.N or acemization was detected in either the coupling or tandemdeprotection/coupling steps (Scheme 48). [88] Balskus and Wallace applied TPGS-750-M/H 2 Ot echnology, previously used solely within the domain of organic chemistry, to the field of biology by combining microbial fermentation and transition-metal catalysis. [89] In synthetic biology,accumulation of the final product within the host living organism can significantly reduce its productivity.O ne way to addresst his obstacle is to remove the product throughout itsf ormation, thus maximizing its titer.W hile organic solvents have been utilized to separate lipophilic metabolites from bacteria, the authors have taken advantageo ft he lipophilic core of micelles as am eans of removing styrene generated by as tyrene-productionp athway in engineered E. coli NST74.…”

Mechanistic Details and Conformational Behavior of Selective Peptide Linkage Facilitated by Aun Clusters

“…The choice of water as the solvent is guided by the fact that detrimental organic solvents are being increasingly replaced with water as prodigious amount of toxic organic solvents to eliminate the excess reagents involved in solidphase techniques of peptide synthesis has become an environment concern [7,8] scientists have replaced the detrimental organic solvents with water in solid-phase techniques. [62][63][64] Two possible reaction pathways (Path-1 and Path-2) have been proposed for this process. [65] In the first path (Path-1) the dipeptide is generated through transfer of a hydrogen atom from the amino group of one amino acid to the carboxyl group of the other amino acid.…”