Hydrolysis benzyl ester

Carboxyl groups of ammo acids and peptides are normally protected as esters Methyl and ethyl esters are prepared by Fischer esterification Deprotection of methyl and ethyl esters is accomplished by hydrolysis m base Benzyl esters are a popular choice because they can also be removed by hydrogenolysis Thus a synthetic peptide protected at both... 

A phenacyl ester is much more readily cleaved by nucleophiles than are othc esters such as the benzyl ester. Phenacyl esters are stable to acidic hydrolysis (e.g coned. HCh HBr/HOAc 50% CF3COOH/CH2Cl2 HF, 0°, 1 h ). 

The p-bromobenzyl ester has been used to protect the /3-COOH group in aspartic acid. It is cleaved by strong acidic hydrolysis (HF, 0°, 10 min, 100% yield), but is stable to 50% CF3COOH/CH2CI2 used to cleave /-butyl carbamates. It is 5-7 times more stable than a benzyl ester. ... 

In a penicillin synthesis, the carboxyl group was protected as a / -bromophenacyl ester that was cleaved by nucleophilic displacement (PhSK, DMF, 20°, 30 min, 64% yield). Hydrogenolysis of a benzyl ester was difficult (perhaps because of catalyst poisoning by sulfur) basic hydrolysis of methyl or ethyl esters led to attack at the /3-lactam ring. ... 

Merck s thienamycin synthesis commences with mono (V-silylation of dibenzyl aspartate (13, Scheme 2), the bis(benzyl) ester of aspartic acid (12). Thus, treatment of a cooled (0°C) solution of 13 in ether with trimethylsilyl chloride and triethylamine, followed by filtration to remove the triethylamine hydrochloride by-product, provides 11. When 11 is exposed to the action of one equivalent of tm-butylmagnesium chloride, the active hydrogen attached to nitrogen is removed, and the resultant anion spontaneously condenses with the electrophilic ester carbonyl four atoms away. After hydrolysis of the reaction mixture with 2 n HC1 saturated with ammonium chloride, enantiomerically pure azetidinone ester 10 is formed in 65-70% yield from 13. Although it is conceivable that... 

Alcalase selectively catalyses the hydrolysis of D,L-amino add methyl and benzyl esters to provide L-amino adds and D-amino add esters with high optical purity (Figure A8.10). 

For the delicate transesterification of a p-Lactam intermediate (for carbacephalosphorin skeleton), where originally hydrolysis of methyl ester was done homogeneously and then formation of the benzyl (or substituted benzyl) ester was done separately, Doecke et al. (1991) have devised a mild and efficient methodology using PTC. A dual use of a PT catalyst, Bu4NBr, in one pot was made in a CH2CI2 - H2O system. In the first step 5N NaOH was used, then the pH was adjusted to 7.2 to 7.8 and subsequently benzyl (or substituted benzyl) bromide was added. 

The pronounced proclivity of phosphoric monoester monoanions to eliminate POf is not always recognizable from the characteristic pH profile of Fig. 1. The hydrolysis rate maximum at pH w 4 may be masked by a faster reaction of the neutral phosphoric ester, as in the case of a-D-glucose 1-phosphate63) or on hydrolysis of monobenzyl phosphate 64). In the latter case, the known ability of benzyl esters to undergo SN1 and SN2 reactions permits fast hydrolysis of the neutral ester with C/O bond breakage. The fact that the monoanion 107 of the monobenzyl ester is hydrolyzed some 40 times faster than the monoanion 108 of the dibenzyl ester at the same pH again evidences the special hydrolysis pathway of 107, rationalized by means of the metaphosphate hypothesis. 

In an effort to address the poor membrane permeation of L-767,679, the benzyl ester pro-drug, L-775,318 was synthesized (Fig. 13.2) The latter compound exhibited significant lipophilicity (log P = 0.7) that was consistent with improved potential to cross the enterocyte membrane. However, this did not lead to a marked improvement in absorption potential (in the rat), as intestinal hydrolysis and counter-transport combined to prevent significant passage of the compound across Caco-2 cells and the rat gut. 

Dimethylaminoethane-2-ol (20) is a compound that, by virtue of its nucleophilic center (Me2NH+C2H40), is employed to convert protected segments bound to supports as benzyl esters into acids by transesterification into dimethylaminoethyl esters [C(=0)0C2H4NMe2] that are hydrolyzable by a dimethylformamide-water (1 1) mixture. Compound 20 readily forms esters from acid chlorides. The hydrolysis and esterification are facilitated by anchimeric assistance by the adjacent nitrogen atom (see Section 2.10). The amino alcohol also reacts with dichloromethane. 

The corresponding acid was expected to be more active than the methyl ester and it was prepared in two ways — by hydrolysis of the methyl ester or hydrogenolysis of the benzyl ester ... 

For the unsubstituted compound 197a-Me the 2R/2S ratio was only 5.6 1 [ 10b, c], yet in this case the absolute configuration was checked by X-ray crystal structure analysis. The a-azidoesters 197-R were converted to the a,)3-diamino acids 198-R as described above, i.e. by catalytic hydrogenation over palladium on charcoal and hydrolysis of the ester group (Scheme 58) [10b, c, 62]. Saponification was not necessary for the benzyl esters 197a,b,i-Bn. 

Table 4. Asymmetric hydrolysis of esters from fluoroalkylated benzyl alcohol...

R)- and (S)-Mandelic acid can also be used to resolve the benzyl esters 39t77 8°l of racemic Tic (Scheme 16).[79] Both isomers of Tic are released by hydrolysis of their respective benzyl esters. This also constitutes a valuable synthetic route. 

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