2,4,5-trichlorophenyl ester

L-Tryptophanyl-L-methionyl-L-aspartyl-L-phenylalanine amide trifluoroacetate N-t-Butyloxycerbonyl- -alanine 2,4,5-trichlorophenyl ester... 

A solution of 3.55 parts of L-trypTtophanyl-L-methionyl-L-aspartyl-L-phenylalanine amide trifluoroacetate in 30 parts of dimethylformamide is cooled to 0 C, and 1.01 parts of tri-ethylamine are added. The mixture is stirred while 1.84 parts of N-tert-butyloxycarbonyl-(3-alanine 2,4,5-trichlorophenyl ester are added at 0 C. The reaction mixture is kept at 0°C for 48 hours and then at 20°-23°C for 24 hours. The mixture is added to a mixture of 100 parts of ice-water, 0.37 part of concentrated hydrochloric acid (SG 1.18), 1.2 parts of acetic acid and 20 parts of ethyl acetate. The mixture is stirred for 15 minutes at 0°-10°C and is then filtered. The solid residue is washed with water and then with ethyl acetate, and is dried at 40°-50°C under reduced pressure. There is thus obtained N-tert-butyloxycarbonyl-)3-alanyl-L-tryptophanyl-L-methionyl-L-aspartyl-L-phenylalanine amide, MP 213°C with decomposition. 

N-tert-Butyloxyca rbony I- -a la nine-2,4,5-trichlorophenyl ester Pentagastrin 3-Butyl-1 -phenylamine Bufeniode 1 -Butyne... 

OTcp 2,4,5-trichlorophenyl ester ONSu N-hydroxysuccinImidyl ester N azide... 

J Pless, RA Boissonnas. On the velocity of aminolysis of a variety of new activated N-protected a-amino-acid phenyl esters, in particular 2,4,5-trichlorophenyl esters. Helv Chim Acta 46, 1609, 1963. 

Synonyms AI3-23284 Blitex BRN 1885571 Caswell No. 724 Dermafos Dermaphos Dimethyl trichlorophenyl thiophosphate 0,0-Dimethyl-0-2,4,5-trichlorophenyl phosphorothio-ate 0,0-Dimethyl 0-(2,4,5-trichlorophenyl)thiophosphate Dow ET 14 Dow ET 57 Ectoral EINECS 206-082-6 ENT 23284 EPA pesticide chemical code 058301 ET 14 ET 57 Etrolene Fenchlorfos Fenchlorophos Fenchchlorphos Karlan Korlan Korlane Nanchor Nanker Nankor NSC 8926 QMS 123 Phenchlorfos Phosphorothioic acid, 0,0-dimethyl 0-(2,4,5-trichlorophenyl) ester Remelt Ronne Rovan Smear, Trichlormetaphos Trichlorometafos Trolen Trolene Trolene 20L Troline Viozene. 

In the early synthesis of deamino-dicarba-oxytocin, the intermediate Z-Asu(OMe)-OH was used which requires a saponification step prior to cyclizationJ1-2 Subsequently, a synthesis more consistent with the general protection strategies in peptide synthesis was developed with the intermediate Z-Asu(OtBu)-OH.12,24 As outlined in Scheme 9, upon selective deprotection of the side-chain carboxy group of the Asu residue by exposure to TFA, the octapeptide derivative 26 is converted into the 2,4,5-trichlorophenyl ester 27 using the tri-fluoroacetate method.129,20 Hydrogenolytic Na-deprotection of 27 in dilute solution leads to... 

Synonym Blitex, Dermafos, Dermaphos, dimethyl trichlorophenyl thiophosphate, Dow ET 14, Dow ET 57, Ectoral, ENT 23284, Etrolene, Fenchlorfos, Fenchlorphos, Gesektin K, Karlan, Korlan, Nanchor, Nanker, Nankor, OMS 123, Phenchlorfos, Remelt, Rovan, trichlorometafos, Trolen, Trolene, Viozene Chemical Name 0,0-dimethyl 0-(2,4,5-trichlorophenyl)thiophosphate 0,0-dimethyl 0-2,4,5-trichlorophenyl phos-phorothioate phosphoric acid 0,0-dimethyl 0-(2,4,5-trichlorophenyl)ester Uses insecticide. 

Carbonic acid, tert-butyl 2,4,5-trichlorophenyl ester (8) Carbonic acid,... 

Silyl esters are stable to nonaqueous reaction conditions, but are often too labile to mild acid or base or even neutral aqueous media to survive many simple manipulations. Thus, they have not found wide application in peptide synthesis. Due to easy formation and cleavage they may play an important role as intermediates in the synthesis of amino acid derivatives and for temporary carboxy protection in the preparation of small peptide fragments. The TMS group has been used for the solubilization of H-Arg-OH for the synthesis of Z-Arg(Z2)-OHP l and in the synthesis of Al -Nps- and Al -Tfa-protected amino acids.P Amino acid trimethylsilyl esters as well as the related A1 -TMS derivatives react rapidly with acylating agents and are used for the preparation of peptides with amino acid active esters, e.g. A-hydroxysuccinimide-, 4-nitrophenyl-, or 2,4,5-trichlorophenyl esters, or mixed anhydrides. 

Nitrophenyl, pentachlorophenyl, and 2,4,5-trichlorophenyl esters have been used for carboxy protection in the so-called backing-offf °l approach, illustrated in the preparation of several activated peptide fragments for convergent peptide syntheses. 

Thus, two types of active esters are of interest those formed from an acid and a substituted phenol (12-15) and those formed from an acid and a substituted hydroxylamine (16-19). Both types are reactive by virtue of the electron-withdrawing properties of the OR moiety in 2. The level of activation of the substituted phenyl esters varies directly with the electronic effect going from 4-nitrophenyl to 2,4,5-trichlorophenyl, pentachlorophenyl, and pentafluorophenyl, which corresponds with the increasing acidity of the phenols. A diminution in the rate of aminolysis is caused by the presence of a substituent in the ortho position of the ring.f l An additional phenomenon contributes to the reactivity of the esters formed from substituted hydroxylamines, namely anchimeric assistance. Since the anoinolysis of active esters is a bimolecular reaction, it is dependent on concentration and can be forced to completion by an excess of one of the reactants. Aminolysis is also characterized by a pronounced dependence on the polarity of the solvent in particular for the esters formed from substituted phenols, the half-life of a 2,4,5-trichlorophenyl ester in the presence of benzylamine being one hundred times less in dimethylformamide than in benzene. Furthermore, aminolysis is catalyzed by mild acid such as acetic acid. The rate of anoinolysis is slowed if the side chain of the active ester contains a P-methyl substituent. 

Compounds such as 4-nitrophenyl and 2,4,5-trichlorophenyl esters of N-protected amino acids were originally prepared also by reaction of the N-protected acids with di- or trisub-stituted esters of carbonic,sulfinic,f l or phosphinic acids l in, or with addition of, pyridine. This was followed by the use of mixed carbonates 54 that served both for acylation of amino acid 53 to N-protected acid 55 and subsequent esterification to 56 using carbodiimide (Scheme 13).A variant of this was the preparation of the unusual l,l,4-trioxo-2,5-di-phenyl-4,5-dihydro-3-thienyl 57 esters of Boc amino acids 56c, which avoided the use of carbodiimide since esterification proceeds in the presence of tetramethylguanidine.P l... 

The preparation in solution of the preformed handle requires the protection of its carboxy group prior to the formation of the ester bond. Phenacyl esters, which can be removed with zinc in acetic acid and are therefore compatible with the presence of both Boc- and Fmoc-protecting groups, have been used.f l An alternative procedure, however, involves the use of 2,6-dichloro- or 2,4,5-trichlorophenyl esters,which serves a dual purpose of first protecting and then activating the carboxy group of the handle. 

A comparison of the rates of reaction of many substituted phenyl esters with N-protected a-amino acids showed that the 2,4,5-trichlorophenyl esters are more reactive than p-nitrophenyl esters and are promising new active derivatives for the synthesis of peptides. One advantage is that the ester group does not interfere with catalytic hydrogenation for removal of the carbobenzoxy group. The esters are prepared by condensation of the N-protected amino aeid and the phenol with dicyclo-hexylcarbodiimide. In the synthesis of a particular hexapeptide, where other methods were unsatisfactory because of poor yields or impure products, Bentley et al. obtained the hexapeptide in 97% yield through the trichlorophenyl ester. J. Pless and R. A. Boissonnas, //elr., 46,1609 (1963)... 

In exploring reagents and conditions for efficient synthesis of peptides with activated esters, Pless and Boissonnas found that the reaction of Cb-L-phenyl-alanine-2,4,5-trichlorophenyl ester (4) with benzylamine is faster in dimethylforma-ci. 

Peptide Synthesis.1 In the presence of triethylamine the reagent reacts with an amino acid to give the N-r-butoxycarbonylamino acid and 2,4,5-trichIorophenol. The two products can be extracted together by ethyl acetate, and if DCC is added the 2,4,5-trichlorophenyl ester of N-/-butoxycarbonylamino acid is obtained ir high yield. This is an active ester suitable for peptide synthesis (1. 1196). 

Phosphorothioic acid, 0,0-dimethyl 0-(2,4,5-trichlorophenyl) ester Fenchlorphos Phenchlorphos H3C0, r Cl Cl 3381, 3633 ... 

These derivatives are stable to extended storage, and yet the p-nitrophenolate anion is a sufficiently good leaving group that reaction with free amino groups occurs readily. 2,4,5-Trichlorophenyl esters are occasionally employed in the same fashion. ... 

A detailed study (Pless and Boissonnas 1963) of the influence of halogen substituents on the reactivity of aryl esters led to the choice of 2,4,5-trichlorophenyl esters. 

Chloroquinolin-8-yl ester N-Hydroxysuccinimide ester 2,4,5-Trichlorophenyl ester Bis-o-phenylene pyrophosphate Silicon tetrachloride 2-Nitrothiophenyl ester... 

Sequence I was synthesized stepwise, starting with phenylalanine amide using tert.-butyloxycarbonyl amino acid p-nitrophenyl esters or 2,4,5-trichlorophenyl esters (Figure 13). In the first stages of this synthesis we were, of course, treading along the path followed by Kenner, Sheppard and coworkers in their synthesis of gastrin. ... 

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