Further applications of classical amide coupling reagents: Microwave‐assisted esterification on solid phase

Abstract

Ester linkage (s) is a key chemical connector in organic chemistry, including natural products, peptides, and synthetic polymers. We herein describe a straightforward method for the efficient formation of ester linkage (s) on solid-phase. This method simply involves the use of amide coupling reagents under microwave irradiation. The robustness of this method relies on the use of classical solid-phase coupling reagents, heating by microwave irradiation, and a short time period, which results in high yields and the minimization of racemization.

γ-Valerolactone (GVL): An eco-friendly anchoring solvent for solid-phase peptide synthesis

“…Satisfactory loading values were observed (Table 1). Amino acid incorporation onto Wang resin requires strong carboxylic acid activation by reaction with carbodiimide [N,Ndiisopropylcarbodiimide (DIC)] in the presence of 10% of either N,N-dimethyl-4-aminopyridine (DMAP) or N-methylimidazol (NMI) as catalysts [20][21][22]. The presence of the basic catalyst has two potential drawbacks, namely racemization [23][24][25][26] and dipeptide formation [24,27], which were both examined in this study, together with the incorporation yield.…”

“…These conditions yielded good results for incorporation and acceptable racemization for all amino acids, except Fmoc-His(Trt)-OH (34.4%, which is close to other values reported in the literature, ref. [22,29]) and Fmoc-Trp(Boc)-OH (15.8%). While it is known that His can easily undergo racemization through the H abstraction of the α-C by the πnitrogen of its imidazole ring [22], more surprising was the high racemization found for Trp(Boc).…”

“…[22,29]) and Fmoc-Trp(Boc)-OH (15.8%). While it is known that His can easily undergo racemization through the H abstraction of the α-C by the πnitrogen of its imidazole ring [22], more surprising was the high racemization found for Trp(Boc). It is worth mentioning that high racemization data were reported for Trp(Boc) in solution-phase peptide synthesis under certain conditions [30].…”

DIC/Oxyma‐based accelerated synthesis and oxidative folding studies of centipede toxin RhTx

“…Peptide‐based drugs have significant therapeutic effects on the treatment of tumor, virus, diabetes, cardiovascular disease, immune disease, and so forth 1–7 . At present, most peptide and peptide‐based drugs are obtained by chemical synthesis, and the Fmoc‐based solid‐phase peptide synthesis (SPPS) method is the most widely used strategy 8–16 . During the SPPS, the coupling reagent plays a key role in the iterative construction of condensation of carboxylic acids with amines, affording the amide bond 10,17,18 .…”

Total Synthesis and Antimicrobial Evaluation of Pagoamide A

“…Solid-phase peptide synthesis (SPPS) is a synthetic platform devised by chemists for the construction of consecutive amide bonds that operates in a similarly modular fashion ( Coin et al, 2007 ). A variety of reagents have been developed for the activation of amino acids ( Takayama et al, 2018 ) to ensure high efficiency in the formation of an amide bond on the solid support (resins). An excess of activated amino acid can be used to drive the reaction to near completion; meanwhile, workup and purification are reduced to simply washing the resins with the appropriate solvents.…”