Protection butyl esters

In each step of the usual C-to-N peptide synthesis the N-protecting group of the newly coupled amino acid must be selectively removed under conditions that leave all side-chain pro-teaing groups of the peptide intact. The most common protecting groups of side-chains (p. 229) are all stable towards 50% trifluoroacetic acid in dichloromethane, and this reagent is most commonly used for N -deprotection. Only /ert-butyl esters and carbamates ( = Boc) are solvolyzed in this mixture. 

The carboxamidomethyl ester was prepared for use in peptide synthesis. It is formed from the cesium salt of an A-protected amino acid and a-chloroacetamide (60-85% yield). It is cleaved with 0.5 M NaOH or NaHCOa in DMF/H2O. It is stable to the conditions required to remove BOC, Cbz, Fmoc, and r-butyl esters. It cannot be selectively cleaved in the presence of a benzyl ester of aspartic acid. ... 

The r-butyl ester is a relatively hindered ester, and many of the methods reported below should be—and in many cases are—equally effective for the preparation of other hindered esters. The related 1- and 2-adamantyl esters have been used for the protection of aspartic acid. ... 

The dibenzosuberyl ester is prepared from dibenzosubeiyl chloride (which is also used to protect —OH, —NH, and —SH groups) and a carboxylic acid (Et N, reflux, 4 h, 45% yield). It can be cleaved by hydrogenolysis and, like t-butyl esters, by acidic hydrolysis (aq. HCl/THF, 20°, 30 min, 98% yield). ... 

Exposure of compound 16, a substance that can be obtained in a straightforward manner from glycine, to sodium tert-butoxide furnishes an enolate that undergoes conversion to 8 upon treatment with terf-butyl formate. It was anticipated that the phthalimido and tert-butyl ester protecting groups in 8 could be removed easily and selectively under anhydrous conditions at a later stage in the synthesis. 

Intermediate D-a-6 must now be converted into a form amenable to the crucial lactamization reaction. To this end, treatment of D-a-6 with hydrazine accomplishes the removal of the phthalimide protecting group and provides D-a-18 (Scheme 5) after acidification with dilute aqueous HC1. It is noteworthy that the acid-labile tert-butyl ester function withstands the latter step. Introduction of the... 

A tert-butyl ester serves as an efficient organyl-stabilizing group for a lithiated aziridine when the N-protecting group is a chelating moiety. Deprotonation/elec-... 

Carboxylic acids can be protected as oxazolines [96, 105-107, 186, 191] or as ester functions. Alkynic esters such as silyl esters [153, 211], tert-butyl esters [216], and even benzyl esters [153, 211] have been successfully hydrozirconated when the reactive site was a terminal alkyne or vinyl group (Scheme 8-27). 

Solutions of butyllithium in hexanes and sec-butyllithium in cyclohexane were purchased from the Aldrich Chemical Company, Inc. It Is recommended that only freshly opened bottles or extremely well protected solutions be used as the presence of lithium butoxide in partially decomposed bottles results in formation of the corresponding butyl ester as an undesired by-product. 

Paulsen and associates (58) synthesized mono- and di-D-galactopyranosyl derivatives of L-serine/L-threonine. Condensation of the 2-azido-2-deoxy-glycosyl halides 61 and 62 with the benzyl or tert-butyl esters of iV-benzyl-oxycarbonyl (Z)-protected L-serine, L-threonine, and L-leucyl-L-serine (63 -65) in the presence of silver carbonate, silver perchlorate, Drierite, and molecular sieves gave (59) the corresponding O-glycopeptides 67-69. The free glycopeptides were obtained after total deprotection. 

FIGURE 3.22 Protection (A) of carboxyl groups of amino acids as ferf-butyl esters,58 (B) of carboxyl groups of /V-substituted amino acids as fert-butyl esters,61 and (C) of phenolic and sulfhydryl groups as ethers. The amino acid esters are isolated as the hydrochlorides. 

B Liberek. Tertiary butyl esters of protected (S-cyano-L-alanine peptides as possible intermediates in the preparation of L-asparaginyl peptides, (peroxide for oxidation) Chem Ind 987, 1961. 

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