Benzyl ester, preparation salts

Benzyl esters. Preparation of benzyl esters by Fischer esterification proceeds with difficulty. An alternative method involves decomposition of benzyldimethylanilinium salts of carboxylic acids in a refluxing inert solvent. 

The excess of alkah is then neutralised with dilute hydrochloric acid (phenolphthalein) and the solution is evaporated to dryness on the water bath. The acid may then be characterised as the S-benzyl-tao-thiuronium salt or as the p-bromophenacyl ester (Section 111,85). In many instances the derivative may be prepared directly from the neutralised solution. 

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. ... 

Oxidation of phenyl hexyl sulphide with sodium metaperiodate gave also only a trace amount of the corresponding sulphoxide72. On the other hand, Hall and coworkers73 prepared benzylpenicillin and phenoxymethyl penicillin sulphoxides from the corresponding benzyl esters by oxidation with sodium metaperiodate in dioxane solution with a phosphate buffer. A general procedure for the synthesis of penicillin sulphoxides was reported later by Essery and coworkers74 which consists in the direct oxidation of penicillins or their salts with sodium metaperiodate in aqueous solution at pH 6.5-7.0. 1-Butadienyl phenyl sulphoxide 4475 and a-phosphoryl sulphoxides 4576 were also prepared by the same procedure. 

HA and three different HA esters, supplied by Fidia Advanced Biomaterials SpA (Padua, Italy), were examined. HA esters were prepared by treating a quaternary ammonium salt of HA with an esterifying agent in a suitable aprotic solvent at a controlled temperature as described in detail elsewhere [2]. In this study we analyzed the following esters ethyl ester (HYAFF7), benzyl ester (HYAFFl 1), and dodecyl ester (HYAFF73 Figure 1). The materials used were both films and powders. Films were obtained by a phase inversion process from DMSO solutions as previously described [2,4]. 

Penicillin is but one of a series of closely related compounds isolated from fermentation broths of Penicillium notatum. This compound, also known as penicillin G (1-1) or benzyl penicillin, is quite unstable and quickly eliminated from the body. Initial approaches to solving these problems, as noted above, consisted of preparing salts of the compound with amines that would form tight ion pairs that in effect provided a controlled release of the active dmg. Research on fermentation conditions aimed at optimizing fermentation yields succeeded to the point where penicillin G or penicillin V (26-1), in which the phenylacetyl group is replaced by phenoxyacetyl, is now considered a commodity chemical. Another result of this research was the identification of fermentation conditions that favored the formation of the deacylated primary amine, 6-aminopenicillanic acid (2-4) or 6-APA, a compound that provided the key to semisynthetic compounds with superior pharmaceutical properties than the natural material. An elegant procedure for the removal of the amide side chain proved competitive with 6-APA from fermentation. This method, which is equally applicable to penicillin V, starts by conversion of the acid to the corresponding silyl ester (2-1). Treatment of that compound with phosphoms pentachloride in the... 

The key intermediate in the preparation of derivatives suitable for peptide synthesis (Table 3) is the benzyl (25)-7V-tritylaziridine-2-carboxylate, since it is smoothly converted into the N-protected imino acid by catalytic hydrogenolysis.[47] Similarly, the related methyl ester is saponified by lithium hydroxide to produce A-tritylaziridine-2-carboxylateJ83 84 Detrit-ylation to benzyl (2S)-aziridine-2-carboxylate is more difficult, but the dibenzosulfimide salt is found to be perfectly stable on storage as a solid for longer periods of time (see Section 9.2.1.1) J47l In solution, upon addition of bases the benzyl ester is sufficiently stable to allow for peptide syntheses.[47]... 

Acid-labile linkers are the oldest and still the most commonly used linkers for carboxylic acids. Most are based on the acidolysis of benzylic C-O bonds. Benzyl esters cleavable under acidic conditions were the first type of linker to be investigated in detail. The reason for this was probably the initial choice of polystyrene as an insoluble support for solid-phase synthesis [13]. Polystyrene-derived benzyl esters were initially prepared by the treatment of partially chloromethylated polystyrene with salts of carboxylic acids (Figure 3.3). 

Seeberger and coworkers prepared synthetically useful amounts of P-peptides (0.2-0.6mmol) by using a microreactor (reactor volume = 78.3 pi). The reaction of add fluoride and the TFA salt of amino acid benzyl ester in the presence of N-methylmorpholine (NMM) at 90 °C (3 min residence time) gave the dipeptide in 92% yield (Scheme 4.19). A fluorous tag method was used for an effident synthesis of tetrapeptides. Amino acid esters having fluorous tags were used to facilitate purification by fluorous solid-phase extraction (FSPE) (Scheme 4.20). 

Successful polymer supported stereoselective Diels-Alder reaction was performed using immobilized enantiopure 4-(3-hydroxy-4,4-dimethyl-2-oxopyrro-lidin-l-yl)benzoic acid 12 as a chiral auxiliary [15]. The corresponding resin-bound acrylate derivate has been applied as the dienophile 13. Preparation of the precursor started with the combination of pantolactone 10 and the sodium salt of 4-aminobenzoic acid. Conversion into the corresponding benzyl ester followed. The obtained racemate was esterified with (lS)-camphanic acid chloride to a dia-stereomeric mixture to gain the enantiopure compounds by chromatographic separation. After subsequent saponification of the camphanic acid moiety and hydrolysis of the benzyl ester the (R)-enantiomer 11 was coupled to Rink amide resin (Scheme 12.6). 

A different approach to the synthesis of tetrathiafulvalenecarboxylic acid esters involves alkylation of the corresponding cesium salts with alkyl halides. In this way, the methyl ester of 65 (92BSB741) and the benzyl esters of 70 and 71 have been prepared (92MI8) (Scheme 29). These cesium salts have also been made to react with poly(p-chloromethylsty-rene) and related copolymers (89MI5 92MI8). 

Amino-acid Protection. - Carboxyamidomethyl (CAM) esters have been shown to be useful protecting groups in a-chymotrypsin and papain-catalysed peptide hydrolysis and synthesis.5 10 1,3-Dioxans (582) can be obtained from Na-protected serine derivatives by acid-catalysed transacetalation and are sufficiently robust to survive both amino deprotection and peptide coupling reactions. 11 (L)-Histidine benzyl ester can be prepared as the ditosylate salt... 

The resin-bound fragment preparation starts with the chlorine displacement from the chloromethylene function on a chloromethylated polystyrene by the cesium salt of Z-L-Cys(Tr)-OH. The resulting benzyl ester is treated with Scm-Cl to form the active intermediate sulfenyl thiocarbonate which is allowed to react with 4-acyloxy-6-mercaptodibenzofuran, preferably in dichloromethane-hexafluoro-2-propanol, with or without catalytic triethylamine (eq 16). ... 

The PEAs reported in this work were prepared in a simple way by solution or interfacial polycondensation, where di-p-toluenesulfonic acid salts of bis-(a-amino acid)-a,co-alkylene diesters react with chlorides of dicarboxylic acids (interfacial polycondensation) or their active diesters (Active Polycondensation, APC). The APC method involves the condensation of two partners (I) bis-electrophilic, activated dicarboxylic acids, and (II) bis-nucleophilic, acid salts of bis-(a-amino acid)-a,(0-alkylene diesters in combination with di-p-toluenesulfonic acid salts of L-lysine benzyl ester. This reaction proceeds under mild conditions in common organic solvents and leads to polymer of high molecular weight (up to 300 KDa). A detailed review of the APC method has been recently summarized by Katsarava (7). 

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