O-Nitrophenyl esters

Diphenylthieno[3,4-d][l,3]dioxol-2-one 5,5-dioxide (304) can serve as an activating agent for peptide synthesis (76AG(E)444). The esters (305) are formed readily on admixture of a carboxylic acid with (304) in an aprotic solvent in the presence of pyridine. The activated esters (305) are stable, crystallizable compounds which react with amines readily to furnish the corresponding amides (Scheme 65). Competition experiments reveal that the esters (305) are more effective acyl transfer agents than the p- and o-nitrophenyl esters often used in peptide synthesis. 

The first reported solid-phase synthesis of head-to-tail cyclic peptides was based on the intramolecular aminolysis of resin-bound o-nitrophenyl esters. The cyclization proceeds concurrently to cleave the peptide from the resin, after deprotection and neutralization of the AT-terminal residue (Scheme 2A). Accordingly, Fridkin et al. [3] reported the preparation of several simple, unhindered cyclopeptides, such as cyc/o(Ala-Gly-Ala-Ala). Similarly, Flanigan and Marshall [4] obtained activation of the resin-bound peptide ester, after elongation of the peptide chain, by oxidation of the 4-(methyl-thio)phenyl (MTP) linker to a sulfonyl ester. Subsquent deblocking of the A-terminal residue and intramolecular condensation yielded the desired cyclic peptide. However, this method was found not to be suitable for the synthesis of longer and more hindered cyclic peptides [5]. 

ORIGIN/INDUSTRY SOURCES/USES intermediate in organic synthesis indicator synthesis of dyestuffs pesticides a reagent for the preparation of o-nitrophenyl esters used in peptide synthesis pharmaceuticals reagent for glucose tests... 

Better reaction rates were observed with the already inherently more reactive o-nitrophenyl esters, in part because they are less sensitive to steric hindrance than their para-substituted analogs. Bulkyness of the activating groups renders N-hydroxysuccinimide esters and pentachlorophenyl esters less well suited for acylation inside the matrix of a polymer than in solution. Only the introduction of the powerful pentafluorophenyl esters led to a revival of the active ester idea in the praxis of solid phase peptide synthesis. Pentafluorophenyl esters of Fmoc amino acids... 

Reagent for prepn. of O-nitrophenyl esters used in peptide synth. Used as EtOH soln. as an acid-base indicator (pH range 5.0-7.0 colourless - yellow). Yellow needles or prisms (EtOH or Et20). Sol. EtOH, C H spar. sol. H2O. Mp 44.9°. Bp 216°. 7.23 (25°). 

---