Hydrolysis ester analogs

The cyclic phosphonate ester analog of the cyclic transition state. Antibodies raised against this phosphonate ester act as enzymes they are catalysts that markedly accelerate the rate of ester hydrolysis. 

A third route developed by this group started with the commercially available alcohol 32," a compound which has also been the subject of considerable process development due to its use as a common intermediate in the synthesis of several HMGR inhibitors.Conversion of 32 to the 4-halo or 4-nitrobenzenesulfonate 33 followed by displacement with sodium cyanide provided 34 in 90% yield, which is the z-butyl-ester analog of 29. It was noted that this procedure was most scaleable employing the 4-chlorobenzenesulfonate 33a due to the instability of the 4-bromo and 4-nitro-analogs to aqueous hydrolysis. Ra-Ni reduction as before provided the fully elaborated side-chain 35 as the f-butyl ester (Scheme 8). 

These results can be summarized in terms of the mechanisms shown in Figure 11 for peptide and ester hydrolysis. Assuming the peptide binds to the enzyme in the manner shown above, the exact ester analog must bind in a different manner, particularly with regard to the active site metal atom. The placement of the peptide carbonyl group on the... 

FIGURE 2-31 A variety of esters and ester analogs that tend to degrade by hydrolysis. [From Environmental Organic Chemistry, by R. P. Schwarzenbach, P. M. Gschwend, and D. M. Imboden. Copyright 1993, John Wiley Sons, Inc. Reprinted by permission of John Wiley Sons, Inc.]. 

TABLE 2-13 Hydrolysis Rates for Some Esters and Six Ester Analogs ... 

DTX4-6 and OA diol esters (57-62) were isolated from cultured Prorocentrum spp. [58-60]. The rapid hydrolysis of the esters by esterases suggests that these less toxic ester analogs are probably the form of toxin stored within, and excreted from, the dinoflageUate ceU. 

Lim et al. [114] synthesized a biodegradable ester analog of polylysine, poly[alpha-(4-aminobutyl)-L-glycolic acid] (PAGA). While the polymer displayed no cytotoxicity, only modest transfection activity was observed. This maybe due to a too fast hydrolysis and, similar to polylysine, the lack of efficient endosomal escape functionality. Another biodegradable cationic polyester, poly (4-hydroxy-L-proline ester) showed similar characteristics [115]. 

At any given temperature, the rate of a reaction between two different chemicals depends not only on the chemicals involved but also on their concentrations (Section 1.6.7). For a hydrolysis reaction that involves the direct action of the neutral species H2O on an alkyl halide, ester, or ester analog molecule, the two concentrations of interest are those of H2O and the chemical undergoing hydrolysis. Because the concentration of H2O is essentially constant in any dilute solution (approximately 55.4 M), the rate of this hydrolysis reaction varies only with changes in the concentration of the hydrolyzable compound,... 

By the action of concentrate aqueous ammonia solution upon esters. This process is spoken of as ammonolysls of the ester, by analogy with hydrolysis applied to a similar reaction with water. If the amide is soluble in water, e.g., acetamide, it may be isolated by distillation, for example ... 

On the basis of the general mechanism for acid catalyzed ester hydrolysis shown in Figure 20 4 write an analogous sequence of steps for the spe cific case of ethyl benzoate hydrolysis... 

In base the tetrahedral intermediate is formed m a manner analogous to that pro posed for ester saponification Steps 1 and 2 m Figure 20 8 show the formation of the tetrahedral intermediate m the basic hydrolysis of amides In step 3 the basic ammo group of the tetrahedral intermediate abstracts a proton from water and m step 4 the derived ammonium ion dissociates Conversion of the carboxylic acid to its corresponding carboxylate anion m step 5 completes the process and renders the overall reaction irreversible... 

The most successful of these products contain high ratios of VP to DMAEMA and are partially quatemized with diethyl sulfate (Polyquaternium 11) (142—144). They afford very hard, clear, lustrous, nonflaking films on the hair that are easily removed by shampooing. More recendy, copolymers with methyl vinyl imidazoliiim chloride (Polyquaternium 16) (145) or MAPTAC (methacrylamidopropyltrimethyl ammonium chloride) (Polyquaternium 28) have been introduced. Replacement of the ester group in DMAEMA with an amide analog as in Polyquaternium 28 results in a resin resistant to alkaline hydrolysis and hence greater utility in alkaline permanent-wave and bleach formulations (see Quaternary ammonium compounds). 

Monocrotaline on alkaline hydrolysis yields retronecine and monocrotic acid, CjHijOg, b.p. 145-6°/18 mm., [a]p 0°, which forms a p-bromo-phenacylester, m.p. 78°,and a methyl ester, b.p. 94-6°/18 mm., characterised by a 2 4-dinitrophenylhydrazone, m.p. 95-6° see below). The acid gives the iodoform reaction and is oxidised by sodium hypobromite to a mixture of dl- and mcso-aa -dimethylsuccinic acids (I). These and other reactions show that monocrotic acid is a -dimethyllaevulic acid (II) and this has been eonfirmed by comparison with a synthetic specimen of the acid. The methyl ester of the synthetie acid forms a mixture of 2 4-dinitrophenylhydrazones, m.p. 108-9° and 121-2°, into which the analogous produet, m.p. 95-6°, first made from methyl monocrotate see above), has also been separated. 

Taft began the LFER attack on steric effects as part of his separation of electronic and steric effects in aliphatic compounds, which is discussed in Section 7.3. For our present purposes we abstract from that treatment the portion relevant to aromatic substrates. Hammett p values for alkaline ester hydrolysis are in the range +2.2 to +2.8, whereas for acid ester hydrolysis p is close to zero (see Table 7-2). Taft, therefore, concluded that electronic effects of substituents are much greater in the alkaline than in the acid series and. in fact, that they are negligible in the acid series. This left the steric effect alone controlling relative reactivity in the acid series. A steric substituent constant was defined [by analogy with the definition of cr in Eq. (7-22)] by Eq. (7-43), where k is the rate constant for acid-catalyzed hydrolysis of an orr/to-substituted benzoate ester and k is the corresponding rate constant for the on/to-methyl ester note that CH3, not H, is the reference substituent. ... 

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