Peptide using active esters

Peptide synthesis. CoupUng reactions in peptide synthesis using active esters are greatly accelerated in the solution phase or the solid phase by addition of 1 -hydroxy benzotriazole. 

Miyazawa T, Nakajo S, Nishikawa M et al. (2001a) a-Chymotrypsin-catalysed peptide synthesis via the kinetically controlled approach using activated esters as acyl donors in organic solvents with low water content incorporation of non-protein amino adds into peptides. J Chem Soc Perk T 1 1 82-86... 

Peptide Coupling. These thiol esters have been used in the synthesis of several dipeptides. Many of the examples involve highly sterically hindered amino acids and result in very good yields and high optical purity (eq A). There are many useful active esters for peptide coupling, such as pentafluorophenol, p-nitrophenol, and jV-hydroxysuccinimide. However, these do not work as well with the hindered amino acids shown in eq 4. Additionally, there are many direct coupling procedures therefore the 2-pyridylthiol esters have not been used frequently. 

With the dicyclohexylcarbodiimide (DCQ reagent racemization is more pronounced in polar solvents such as DMF than in CHjCl2, for example. An efficient method for reduction of racemization in coupling with DCC is to use additives such as N-hydroxysuccinimide or l-hydroxybenzotriazole. A possible explanation for this effect of nucleophilic additives is that they compete with the amino component for the acyl group to form active esters, which in turn reaa without racemization. There are some other condensation agents (e.g. 2-ethyl-7-hydroxybenz[d]isoxazolium and l-ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline) that have been found not to lead to significant racemization. They have, however, not been widely tested in peptide synthesis. 

Polymer-supported esters are widely used in solid-phase peptide synthesis, and extensive information for this specialized protection is reported annually. Some activated esters that have been used as macrolide precursors and some that have been used in peptide synthesis are also described in this chapter the many activated esters that are used in peptide synthesis are discussed elsewhere. A useful... 

Polymer-supported esters are widely used in solid-phase peptide synthesis, and extensive information on this specialized protection is reported annually. Some activated esters that have been used as macrolide precursors and some that have been used in peptide synthesis are also described in this chapter the many activated esters that are used in peptide synthesis are discussed elsewhere. A useful list, with references, of many protected amino acids (e.g., -NH2, COOH, and side-chain-protected compounds) has been compiled/ Some general methods for the preparation of esters are provided at the beginning of this chapter conditions that are unique to a protective group are described with that group/ Some esters that have been used as protective groups are included in Reactivity Chart 6. 

This active ester was used for carboxyl protection of Fmoc-serine and Fmoc-threonine during glycosylation. The esters are then used as active esters in peptide synthesis. 

A general step ahead in polycondensation was achieved by the application of the active ester method by DeTar et al.19) and Kovacs et al.291 Very soon, the nitrophenyl ester, the pentachlorophenyl ester, or the hydroxysucdnimido ester were used exclusively. The esters of the protected tripeptides could be purified by crystallization, then the N-protecting group was split off and the free peptide esters were purified again. Addition of base starts the polycondensation, resulting quickly in the formation of a viscous solution at low temperature. 

Activated esters for use in peptide-coupling reactions were produced by photolysis of optically active chromium aminocarbenes with alcohols which are good leaving groups, such as phenol, pentafluorophenol, 2,4,5-trichlorophenol, and N-hydroxysuccinimide (Table 17) [ 109]. Since arylcarbenes bearing the op-... 

Recently, a very interesting preparation of P-peptides has been carried out by Kanerva and coworkers through a two-step lipase-catalyzed reactions in which N-acetylated P-amino esters were first activated as 2,2,2-trifluoroethyl esters with CALB [55]. The activated esters were then used to react with a P-aminoester in the presence of CALA in dry diethylether or diisopropylether (Scheme 7.31). In this peptide synthesis, the aminoester was used in excess and the unreacted counterpart was easily separated and later recyded. 

The reaction of dipyridyl disulphide with triphenylphosphine to give the stable phosphonium salt (51) has been used in new methods of phosphorylation (reaction A), in peptide synthesis (reaction B), and in the formation of active esters of cx-amino-acids (reaction C). These reactions appear to have synthetic potential. 

The pairs of dyes more commonly used to generate FRET have been extensively reviewed [86-88] and their conjugation to different types of molecules has been facilitated by the incorporation of a range of reactive groups. Some examples are activated esters and iso thiocyanates for reaction with amino groups of proteins or peptides,... 

The earliest published example of microwave-assisted SPOS involved diisopropyl-carbodiimide (DlC)-mediated solid-phase peptide couplings [24], Numerous Fmoc-protected amino acids and peptide fragments were coupled with glycine-preloaded polystyrene Wang resin (PS-Wang) in DMF, using either the symmetric anhydride or preformed N-hydroxybenzotriazole active esters (HOBt) as precursors (Scheme 12.1). 

Activated esters (see Section 2.9) Activated esters of peptides are rarely used because there is no general method available for converting an (V -protected peptide into the ester with a guarantee that it will be a single isomer. Attempts have been made to overcome this obstacle (see Section 7.8). However, solid phase synthesis allows the preparation of thioesters of segments (see Section 7.10). Once the ester is in hand, it can be aminolyzed without generation of a second isomer if suitable conditions are employed. 

Activated esters (see Section 2.9) with 1-hydroxybenzotriazole as a catalyst are employed — pentafluorophenyl or 4-oxo-3,4-dihydrobenzotriazin-3-yl esters in particular for continuous-flow systems and special cases such as dicarboxylic amino acids. Other activated esters are not reactive enough. An alternative is preparation of benzotriazolyl esters using a carbodiimide followed by addition of the solution to the peptide-resin. 

---