Transacylation catalysis

Catalysis in Transacylation Reactions. The principal objective of the study was to evaluate 4 as an effective organic soluble lipophilic catalyst for transacylation reactions of carboxylic and phosphoric acid derivatives in aqueous and two-phase aqueous-organic solvent media. Indeed 4 catalyzes the conversion of benzoyl chloride to benzoic anhydride in well-stirred suspensions of CH2CI2 and 1.0 M aqueous NaHCC>3 (Equations 1-3). The results are summarized in Table 1 where yields of isolated acid, anhydride and recovered acid chloride are reported. The reaction is believed to involve formation of the poly(benzoyloxypyridinium) ion intermediate (5) in the organic phase (Equation 1) and 5 then quickly reacts with bicarbonate ion and/or hydroxide ion at the interphase to form benzoate ion (Equation 2 and 3). Apparently most of the benzoate ion is trapped by additional 5 in the organic layer or at the interphase to produce benzoic anhydride (Equation 4), an example of normal phase-... 

The importance of hydrophobic binding interactions in facilitating catalysis in enzyme reactions is well known. The impact of this phenomenon in the action of synthetic polymer catalysts for reactions such as described above is significant. A full investigation of a variety of monomeric and polymeric catalysts with nucleophilic sites is currently underway. They are being used to study the effect of polymer structure and morphology on catalytic activity in transacylation and other reactions. 

The systems described in this chapter possess properties that define supramolecular reactivity and catalysis substrate recognition, reaction within the supermolecule, rate acceleration, inhibition by competitively bound species, structural and chiral selectivity, and catalytic turnover. Many other types of processes may be imagined. In particular, the transacylation reactions mentioned above operate on activated esters as substrates, but the hydrolysis of unactivated esters and especially of amides under biological conditions, presents a challenge [5.77] that chemistry has met in enzymes but not yet in abiotic supramolecular catalysts. However, metal complexes have been found to activate markedly amide hydrolysis [5.48, 5.58a]. Of great interest is the development of supramolecular catalysts performing synthetic... 

Chao, Y., Weisman, G. R., Sogah, G. D. Y., Cram, D. J., Host-guest complexation. 21. Catalysis and chiral recognition through designed complexation of transition-states in transacylations of amino ester salts. J. Am. Chem. Soc. 1979, 101,... 

Mathias, L.J. and Vaidya, R.A. (1986) Inverse phase transfer catalysis. First report of a new class of interfacial reactions./. Am. Chem. Soc., 108, 1093. Fife, W.K. and Xin, Y. (1987) Inverse phase-transfer catalysis probing its mechanism with competitive transacylation. J. Am. Chem. Soc., 109, 1278. 

Amide hydrolysis is energetically more demanding than ester hydrolysis or transacylation, and its catalysis by antibodies represents a formidable challenge. Although phosphonamidates would appear to be excellent transition-state analogs, numerous attempts in many laboratories to use these compounds to produce... 

The results of these studies and others reported previously demonstrate that the 1-oxypyridinyl group is an effective catalyst for the transacylation reactions of derivatives of carboxylic and phosphoric acids when incorporated in small molecules and polymers. Furthermore, this catalytic site exhibits high selectivity for acid chlorides in the presence of acid anhydrides, amides, and esters. Therefore, catalysts bearing this group as the catalytic site can be used successfully in synthetic applications that require such specificity. The results of this work suggest that functionalized polysiloxanes should be excellent candidates as catalysts for a wide variety of chemical reactions, because they combine the unique collection of chemical, physical, and dynamic-mechanical properties of siloxanes with the chemical properties of the functional group. Finally, functionalized siloxanes appear to mimic effectively enzyme-lipophilic substrate associations that contribute to the widely acknowledged selectivity and efficiency observed in enzymic catalysis. 

W.P. Jencks, Structure-Reactivity Correlations and General Acid-Base Catalysis in Enzymic Transacylation Reactions, Cold Spring Harbor Symp. Quant. Biol, 1971, 36, 1. 

Fife, W. C., and Y. Xin, Inverse Phase Transfer Catalysis Probing the Mechanism with Competitive Transacylation, /. Amer. Ghem. Soc., 109, 1278 (1987). 

A second strategy, more analogous with the syntheses of crown ethers with transacylation capabihties, is to use primary ammonium ions with the potential substrate in the substituent R of the ammonium ion the dihydropyridine is attached to the crown ether (eq. 18). This approach poses restrictions on the types of reactions that can be carried out because there is no built-in possibility for electrophilic catalysis within the complex. 

The present discussion was intended to analyze molecular recognition in substrate binding. Of course molecular recognition also plays a major role in molecular catalysis and transport processes where transformation or translocation of the bound substrates is brought about by a suitably functionalized receptor molecule. These most important aspects are however beyond the scope of this presentation. One may just note, for the sake of illustration, that for instance cysteinyl derivatives of receptor (12 b) display marked chiral recognition in transacylation reactions with optically active substrates [26] and that dicarboxylate-dicarboxamide analogs of (12 b) allow pH regulation of the Ca /K selectivity in competitive transport of calcium and potassium ions [27]. Further information about the results obtained in the areas of molecular catalysis and transport may be found respectively in the references [28] and [29] and in the references cited therein. 

Yet another full paper from the Cram group details the catalysis of transacylation of the 4-nitrobenzoate esters of several a-amino-acid salts by the thiol-crown (100), and the extent of chiral discrimination shown by the (5)-catalyst in favour of L-amino-acid substrates. These results are rationalized in terms of a model for preferred transition-state complexation cf. 1, 422). 

The previous section demonstrated that chiral macrocyclic polyether hosts discriminate in complexation reactions in chloroform solution between enantiomers of amino ester salt guests. With these results can we go one step further and mimic a catalytic site We will now describe the design of a host that upon complexation with a-amino ester salts produces a transition state intermediate corresponding to a transacylation (thiolysis) reaction between the chiral host catalytic group (thiol) and the enantiomeric guest salts (143). However, it should immediately be realized that these model systems mimic only the acylation step encountered in serine protease catalysis. So far no acceleration in rate has been observed for the deacylation step. 

Crown ether systems which display both binding selectivity and chiral recognition have potential in the field of enzyme models, and an important step in this direction is a report of the catalysis of transacylation of amino-acid p-nitro-phenylesters in ethanol by crown compound (60). There is evidence for a thioester intermediate, and the observation that (S)-host is the more efficient catalyst with (L)-guests can be rationalized by consideration of models for the hypothetical tetrahedral intermediate (61) in the thiolysis. ... 

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