Esters protecting carboxylic acids with

The base hydrolysis data for these compounds are listed in Table 4.5. It is noteworthy that the last four compounds exhibited markedly increased hydrolysis rates in comparison with Me-and Ph-substituted octams (133)-(139). Compound (140) was obtained using the Bu -ester-protected carboxylic acid (32). 

Peptide synthesis requires the use of selective protecting groups. An N-protected amino acid with a free carboxyl group is coupled to an O-protected amino acid with a free amino group in the presence of dicydohexvlcarbodi-imide (DCC). Amide formation occurs, the protecting groups are removed, and the sequence is repeated. Amines are usually protected as their teit-butoxy-carbonyl (Boc) derivatives, and acids are protected as esters. This synthetic sequence is often carried out by the Merrifield solid-phase method, in which the peptide is esterified to an insoluble polymeric support. 

N-Silylated peptide esters are acylated by the acid chloride of N-Cbo-glycine to N-acylated peptide bonds [11]. Likewise, acid chlorides, prepared by treatment of carboxylic acids with oxalyl chloride, react with HMDS 2 at 24°C in CH2CI2 to give Me3SiCl 14 and primary amides in 50-92% yield [12]. Free amino acids such as L-phenylalanine or /5-alanine are silylated by Me2SiCl2 48 in pyridine to 0,N-protected and activated cyclic intermediates, which are not isolated but reacted in situ with three equivalents of benzylamine to give, after 16 h and subsequent chro-... 

Ester formation is the main and most efficient means of protecting carboxylic acids. The protection of a carboxylic acid as an amide is infrequent, as its removal normally requires drastic conditions. Most of the work concerned with the use of light-sensitive protecting-groups for carboxylic acids is in peptide synthesis. Carboxylic acids are protected as photosensitive esters, including ester linkages to polymer supports or as (difficult to prepare) photosensitive amides. Many of these techniques may be readily applied to sugar acids. 

In solution-phase peptide synthesis, acylation of amino acids or peptides with N-protected azetidine-2-carboxylic acid is performed via the active esters, e.g. A-hydroxysuccin-imide 100 111-112 or pentachlorophenyl ester, m 117 as well as by the mixed anhydride 101114 or carbodiimide 118 methods. An attempt to prepare the A-carbonic acid anhydride by cycli-zation of A-(chloroformyl)azetidine-2-carboxylic acid with silver oxide in acetone or by addition of triethylamine in situ failed, presumably due to steric hindrance. 111 In SPPS, activation of the Fmoc-protected imino acid by HBTU 119,120 is reported. In solution-phase peptide synthesis, coupling of N-protected amino acids or peptides to C-protected azetidine-2-carboxylic acid or related peptides may be performed by active esters, 100 118 121 mixed anhydrides, 95 or similar methods. It may be worth mentioning that the probability of pip-erazine-2,5-dione formation from azetidine-2-carboxylic acid dipeptides is significantly reduced compared to proline dipeptides. 111 ... 

Other esters are sometimes used to protect carboxylic acids, especially when there is a desire to deprotect the acid by using different conditions from those available for methyl esters. Benzyl esters are prepared in the usual manner but can be cleaved by reaction with hydrogen and a catalyst. Again it is the benzylic carbon-oxygen bond that is broken in the hydrogenolysis reaction ... 

Methyl and ethyl esters of carboxylic acids are successfully cleaved with bis(tri- -butyltin) oxide to give the free carboxylic acids even in the presence of other functional groups and/or protecting groups (Equation (94)).257... 

Carboxylic acids are protected as their esters such as methyl esters, tert-hutyl esters, allyl esters, benzyl esters, phenacyl esters and alkoxyalkyl esters. The esters are formed by the reaction of carboxylic acid with alcohol, and the reaction is known as esterification. 

Waxes are mixtures of esters of long-chain carboxylic acids with long-chain alcohols. The carboxylic acid usually has an even number of carbons from 16 through 36, while the alcohol has an even number of carbons from 24 through 36. One of the major components of beeswax, for instance, is tria-conty hexadecanoate, the ester of the C30 alcohol triacontanol and the Cib acid hexadecanoic acid. The waxy protective coatings on most fruits, berries, leaves, and animal furs have similar structures. 

A new type of copolymer resist named ESCAP (environmentally stable chemical amplification photoresist) has recently been reported from IBM [163], which is based on a random copolymer of 4-hydroxystyrene with tert-butyl acrylate (TBA) (Fig. 37), which is converted to a copolymer of the hydroxystyrene with acrylic acid through photochemically-induced acid-catalyzed deprotection. The copolymer can be readily synthesized by direct radical copolymerization of 4-hydroxystyrene with tert-butyl acrylate or alternatively by radical copolymerization of 4-acetoxystyrene with the acrylate followed by selective hydrolysis of the acetate group with ammonium hydroxide. The copolymerization behavior as a function of conversion has been simulated for the both systems based on experimentally determined monomer reactivity ratios (Table 1) [164]. In comparison with the above-mentioned partially protected PHOST systems, this copolymer does not undergo thermal deprotection up to 180 °C. Furthermore, as mentioned earlier, the conversion of the terf-butyl ester to carboxylic acid provides an extremely fast dissolution rate in the exposed regions and a large... 

Conversion of this salt to an amide requires temperatures too high for the survival of the peptide, therefore we must convert the carboxyl group to a more reactive acyl derivative, that is, we must "activate" the carboxyl function. However, we do not have to activate the carboxyl group prior to amidation instead we treat the N-protected amino acid with the ester of the second amino acid (remember we must use the ester form in order to block the carboxyl function) in the presence of dicyclohexylcarbodiimide (DCC), a potent non-acidic dehydrating agent ... 

A more commonly used carboxylic-acid-protecting group that is rather more stable towards attack by nucleophiles is the t-butyl ester. t-Butyl esters can be made by reacting the carboxylic acid with the cation generated from isobutene in sulfuric acid. 

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