Activated acyl derivative

It therefore appeared that a general mechanism for enzymatic esterification of phenolic acids with glucose was operative, whereas the reaction with other alcoholic moieties proceeded via carboxyl-activated acyl derivatives. [In this context it should be emphasized that glucose esters must not be confused with glucosides different enzymes are involved in the biosynthesis of these two types of phenolic glucose derivatives (36)]. 

Many such activated acyl derivatives have been developed, and the field has been reviewed [7-9]. The most commonly used irreversible acyl donors are various types of vinyl esters. During the acylation of the enzyme, vinyl alcohols are liberated, which rapidly tautomerize to non-nucleophilic carbonyl compounds (Scheme 4.5). The acyl-enzyme then reacts with the racemic nucleophile (e.g., an alcohol or amine). Many vinyl esters and isopropenyl acetate are commercially available, and others can be made from vinyl and isopropenyl acetate by Lewis acid- or palladium-catalyzed reactions with acids [10-12] or from transition metal-catalyzed additions to acetylenes [13-15]. If ethoxyacetylene is used in such reactions, R1 in the resulting acyl donor will be OEt (Scheme 4.5), and hence the end product from the acyl donor leaving group will be the innocuous ethyl acetate [16]. Other frequently used acylation agents that act as more or less irreversible acyl donors are the easily prepared 2,2,2-trifluoro- and 2,2,2-trichloro-ethyl esters [17-23]. Less frequently used are oxime esters and cyanomethyl ester [7]. S-ethyl thioesters such as the thiooctanoate has also been used, and here the ethanethiol formed is allowed to evaporate to displace the equilibrium [24, 25]. Some anhydrides can also serve as irreversible acyl donors. 

Write the equations for the reaction of a given amino acid with (a) a given alcohol and H+, and (b) acetic anhydride or another activated acyl derivative. 

The mechanism for DCC coupling is not as complicated as it may seem. The car-boxylate ion adds to the strongly electrophilic carbon of the diimide, giving an activated acyl derivative of the acid. This activated derivative reacts readily with the amine to give the amide. In the final step, DCU serves as an excellent leaving group. The cyclohexane rings are miniaturized for clarity. 

The loading module comprises three domains. The first (CL) shows homology to ATP-dependent carboxylic acid-CoA ligases, the second is a putative enoyl reductase (ER) and the third an ACP. The probable sequence of operations starts with the enoic acid 74 derived from shikimic acid which is reduced by the ER domain. The first domain will activate the carboxylic acid to an active acyl derivative ready for transfer to the thiol residue of the ACP. The final saturated product will end up attached to the ACP as a thioester derivative ready for transfer to the KS domain of the first chain extension module. The timing of the reduction in this sequence of operations cannot be predicted. 

Chapter 24 Amino Acids, Peptides, and Proteins Formation of an activated acyl derivative... 

The reactions of lipids represent many reactions that we have studied in previous chapters, especially reactions of carboxylic acids, alkenes, and alcohols. Ester hydrolysis (e.g., saponification) liberates fatty acids and glycerol from triacylg-lycerols. The carboxylic acid group of a fatty acid can be reduced, converted to an activated acyl derivative such as an acyl chloride, or converted to an ester or amide. Alkene functional groups... 

In another approach, the C-2 position of taxol is the site of manipulation. Thus, a two-step enzymatic acylation in organic solvents has been employed to synthesize water-soluble taxol (paclitaxd) derivatives. In the first step, taxol 241 is reacted with the bifunctional acylating reagent 282, as catalyzed by thermolysin (from Bacillus thermoproteolyticus rokko), to give the activated acyl derivative 283. This is then used as a complex acyl donor in the second step [204]. 

Although malonate derivatives were described previously, one example is included here to demonstrate their use as a carboxyl enolate. Reaction of 4.87 with carbonyl diimidazole (CDI, see chapter two, section 2.4) gave the acyl imidazole (a very highly activated acyl derivative), which reacted with the magnesium enolate of... 

Reduction of amides is one of the most frequendy used methods of preparing amines. The method is very versatile because primary, secondary, and tertiary amines are easily prepared from the corresponding classes of amide. Amides are prepared by acylation of amines using activated acyl derivatives such as acid chlorides or acid anhydrides (Section 21.7). 

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