Acyl phosphate biological reactivity

Electronically, we find that strongly polarized acyl compounds react more readily than less polar ones. Thus, acid chlorides are the most reactive because the electronegative chlorine atom withdraws electrons from the carbonyl carbon, whereas amides are the least reactive. Although subtle, electrostatic potential maps of various carboxylic add derivatives indicate the differences by the relative blueness on the C-O carbons. Acyl phosphates are hard to place on this scale because they are not used in the laboratory, but in biological systems they appear to be somewhat more reactive than thioesters. 

Treatment of the enzyme with acyl phosphate in the complete absence of reduced cofactor has allowed the thiol enzyme derivative to be prepared and separated from its reaction mixture. This in turn has permitted considerable characterization of the enzyme thiol. No special cofactor is involved. The thiol of a cysteine residue from the main peptide chain of the enzyme provides the reactive centre. This enzyme demonstrates that the acyl transfer role of thioesters in biological systems is not restricted to phosphopantetheine and dihydrolipoate derivatives. The reactions of the... 

The aldehyde intermediate can he isolated if 1 equivalent of the less reactive reducing agent diisobutylaluminum hydride (DIBAH) is used instead of LiAlH4. The reaction is carried out at 78 °C to avoid further reduction to the alcohol. Such partial reductions of carboxylic acid derivatives to aldehydes also occur in numerous biological pathways, although the substrate is either a thioester or an acyl phosphate rather than an ester. We ll see an example in Section 16.8. 

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