Esters nucleophiles

Bruice, T. C., T. H. Fife, J. J. Bruno, and N. E. Brandon, Hydroxyl group catalysis. II. The reactivity of the hydroxyl group to serine. The nucleophilicity of alcohols and the ease of hydrolysis of their acetyl esters nucleophilicity as related to their pK s , Biochemistry, 1,7-12 (1962). 

A variation on this asymmetric catalytic allylation scheme employed (3-diketones or (3-keto ester nucleophiles with allyl ethers and a palladium-DIOP catalyst.434 The chiral center generated is now one carbon removed from the allyl ligand. As a result, somewhat lower optical yields were observed (-10% equation 353). A variety of chiral phosphines were evaluated in the cyclization of (3-keto esters. Optical yields up to 48% were measured in these reactions435... 

The free glycine ethyl ester nucleophilically attacks the mixed anhydride specifically at the amino acid carbonyl, rather than the carbethoxycarbonyl group, liberating carbon dioxide and ethanol and forming the acylated dipeptide ester in good yield. 

No examples of simple organocatalytic kinetic resolution of dicarboxylic acid anhydrides, e.g. by alcoholysis (Scheme 13.1, middle, X = CR2) seem to have been reported. This type of transformation requires that one anhydride enantiomer remains unchanged while the other is transformed to a mono-ester. Nucleophilic catalysts such as cinchona alkaloids have been shown to effect parallel kinetic resolution, that is, the two enantiomers of the anhydride are converted to regioiso-meric esters. This type of transformation is therefore discussed in Section 13.1.3. 

This enzymatic process may be applied to modifying protein functionality as well. Provided that a hydrophilic protein (substrate) and a highly hydrophobic or lipophilic amino acid ester (nucleophile) are used, it would be possible to obtain a product (P3 in Figure 1) with a structure such that hydrophilic and lipophilic regions in the molecule are localized from each other. It is expected, as a consequence, that a proteinaceous surfactant with an adequately amphiphilic function would be produced. 

All of the data from Table II indicate that, under the unconventional conditions intentionally set in the present study, papain can catalyze the aminolysis of the ES intermediate that probably occurs from succinylated asi-casein (substrate) and papain (enzyme) by L-norleucine n-dodecyl ester (nucleophile), with formation of a surface-active 20,000-dalton product to which this lipophilic nucleophile is attached covalently as illustrated in Figure 1. The observed amphiphilic function of the 20,000-dalton product is probably a result of the formation of a localized hydro-... 

Table III. Conditions Used to Improve the Functionality of Gelatin (Substrate) Through Covalent Attachment of L-Leucine n-Alkyl Ester (Nucleophile) with the Use of Papain (Enzyme)...

This reaction, when applied to a mixture of a hydrophilic protein (substrate) and a lipophilic L-leucine n-alkyl ester (nucleophile), can produce a proteinaceous surfactant with proper amphiphilic functions (see Figure 4). 

As in related esters, nucleophilic attack by water on the carbonyl group will lead to expulsion of the phenolic eseroline, and to the unstable carbamic acid, CH3NH(C=0)-0H, which decomposes further to carbon dioxide and mefhyla-mine. The rate of such a reaction is considerably lower for carbamates than for similar esters [10], due to a lower positive charge on the carbonyl carbon in the carbamate group. This reduced activity of carbamates with water is reflected in the interaction of carbamates with AChE, as discussed in the following section. 

The carbon-sulfur bond of a thioester is rather long—typically on the order of 180 pm—and delocalization of the sulfur lone-pair electrons into the rr orbital of the carbonyl group is not as effective as in esters. Nucleophilic acyl substitution reactions of thioesters occur faster than those of simple esters. A number of important biological processes involve thioesters several of these are described in Chapter 26. 

This transformation can also be achieved using malonates and P-keto ester nucleophiles. Tietze and Raschke have used a silane-terminated Heck reaction, in which the substrate (10.151) loses the silyl group to give the cyclised product (10.152). Incorporation of a nitrogen atom at the requisite position in the side chain allows the enantioselective synthesis of tetrahydroisoquinolines and benzazepines using this methodology. ... 

SCHEME 4 Attempted installation of an a-azido ester nucleophile. 

Esters, Nucleophilic Substitution on the Unsaturated Carbon Atom... 

Symmetric Anhydrides and Esters. Nucleophilic Substitution of Acyl Chloroformates... 

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