Transacylation reaction, acyl transfer

Transacylation is the transfer of the acyl group from one G group to another, resulting in the formation of various acid derivatives. Figure 16-1 summarizes the transacylation reactions. Notice that the more reactive derivatives are convertible to the less reactive ones. Because acetic anhydride reacts less violently, it is used instead of the more reactive acetyl chloride to make derivatives of acetic acid. In aqueous acid, the four kinds of carboxylic acid derivatives in the figure are hydrolyzed to RCOOH in base, to RCOO". 

In this chapter, we describe results from a series of experiments in which phase-transfer catalysts bearing the 1-oxypyridinyl group were used in a variety of transacylation reactions. These reactions include acid anhydride synthesis, as well as hydrolysis of a mixed anhydride and two acyl chlorides. The reactions were carried out in vigorously stirred suspensions of dichloromethane and water. Particular attention was directed to molecular size (monomeric, dimeric, and oligomeric species), structural characteristics (vinyl versus siloxane chain), and solubility (water versus dichloromethane) of the catalysts. 

An 8-amino-3,6-dioxaoctanoic acid moiety, designated as the O monomer or AEEA-OH, is the commonly used spacer and is available suitably protected for use with both Fmoc and f-Boc chemistries (Fig. 9). The O spacer often improves the product yields particularly for solution labeling. This is partially due to the hydrophilic character of the O spacer, which increase the aqueous solubility of PNA oligomers. The placement of an O spacer at the amine terminus effectively prevents acyl transfer rearrangement, a side reaction observed with the standard monomer in basic solutions. This addition of an A-terminal O spacer to the sequence also allows Fmoc-on purification of the PNA oligomer because no transacylation reaction occurs during the Fmoc removal (see earlier). 

However, the salts can be used as valuable transacylating agents, particularly for alcohols, and in this application the salt is not isolated but reacted in situ with the alcohol. An excess of pyridine is needed and such reactions were carried out in pyridine both as reagent and as solvent. Unfortunately, pyridine is difficult to remove from the products, and its use has been superseded by DMAP [4-(A,A-dimethylamino)pyridine]. Now, after A-acylation the 4-A,A-dimethylamino group reinforces the nucleophilicity of the corresponding acylpyridinium salt (Scheme 2.6b), and this promotes the transfer of the acyl group from the salt to the alcohol in the next step. Only a catalytic amount of DMAP is used. 

Transacylation reversible transfer of acyl groups (R-CO-) from a donor to an acceptor, e.g. transfer of the acyl residue CH3-CO- from acetyl-CoA to an acceptor Y CH3-CO - S-CoA -t Y -> CH3-CO-Y + CoA. T. is catalysed by transacylases, which are important in the synthesis and degradation of fatty acids, synthesis of conjugated bile acids via cholic acid-CoA compounds, and other reactions such as acetylation of amino acids and amines. 

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