Acyl transfer reactions, biological

Aside from being fundamentally interesting and industrially important, phosphoryl and acyl transfer reactions are key biological processes. Numerous enzymes con-... 

The preparation of stereochemically-enriched compounds by asymmetric acyl transfer using chiral nucleophihc catalysts has received significant attention in recent years [1-8]. One of the most synthetically useful and probably the most studied acyl transfer reaction to date is the kinetic resolution (KR) of ec-alcohols, a class of molecules which are important building blocks for the synthesis of a plethora of natural products, chiral ligands, auxiliaries, catalysts and biologically active compounds. This research area has been in the forefront of the contemporary organocatalysis renaissance [9, 10], and has resulted in a number of attractive and practical KR protocols. 

Nucleophilic acyl substitution is a common reaction in biological systems. These acylation reactions are called acyl transfer reactions because they result in the transfer of an acyl group from one atom to another (from Z to Nu in this case). 

Comprehensive Biological Catalysis—a Mechanistic Reference Volume has recently been published. The fiiU contents list (approximate number of references in parentheses) is as follows S-adenosylmethionine-dependent methyltransferases (110) prenyl transfer and the enzymes of terpenoid and steroid biosynthesis (330) glycosyl transfer (800) mechanism of folate-requiring enzymes in one-carbon metabohsm (260) hydride and alkyl group shifts in the reactions of aldehydes and ketones (150) phosphoenolpyruvate as an electrophile carboxyvinyl transfer reactions (140) physical organic chemistry of acyl transfer reactions (220) catalytic mechanisms of the aspartic proteinases (90) the serine proteinases (135) cysteine proteinases (350) zinc proteinases (200) esterases and lipases (160) reactions of carbon at the carbon dioxide level of oxidation (390) transfer of the POj group (230) phosphate diesterases and triesterases (160) ribozymes (70) catalysis of tRNA aminoacylation by class I and class II aminoacyl-tRNA synthetases (220) thio-disulfide exchange of divalent sulfirr (150) and sulfotransferases (50). 

As mentioned in the Introduction, imidazole is found in biologic systems and, as mentioned, is quite robust chemically. For example, the imidazole ring system is not readily oxidized Y-oxidation does not readily occur. Very powerful oxidizing agents are required to oxidize the imidazole ring. Chemically, this was recently reported by the use of trimethylsilyl fluorosulfonyldifluoroacetate (TFDA). Mechanistically, this proceeds similar to the acyl transfer reaction described earlier. 

Involved in biological acyl transfer reactions. A related... 

Thioesters and oxoesters are similar in their rates of nucleophilic acyl substitution, except with amine nucleophiles for which thioesters are much more reactive. Many biological reactions involve nucleophilic acyl substitutions referred to as acyl transfer reactions. The thioester acetyl coenzyme A is an acetyl group donor to alcohols, amines, and assorted other biological nucleophiles. 

Bennet AJ, Brown RS. Physical organic chemistry of acyl transfer reaction. In Sinnott M, ed. Comprehensive Biological Catalysis A Mechanistic Reference, vol. 1. New York, NY Academic Press 1997 293—326. 

Mechanisms may be readily envisaged where this reaction may lead to phos-phoryl transfer through nucleophilic attack with ring opening on phosphorus followed by hydrolysis of the acyclic acyl phosphate. In biological systems this may function as an alternative to the metaphosphate reaction. 

In biological systems, related reactions of acyl transfer occur by way of O... 

CpX)Re(CO)3 where X is an acyl group (-COR) in which R carries the biomolecules of interest to target the Re(CO)3 fragment to the required biological site. The so-called double-ligand-transfer reactions also provide a mild synthesis of (CpX)Re(CO)3 derivatized with biomolecules. ... 

Thus the biological importance of the phosphopantetheine group as a catalytic centre is widespread. Numerous examples of the role of coenzyme A are known and the list of phosphopantetheine enzyme centres is growing. The principal reactive element is the thiol, although other attributes of the unique peptide will undoubtedly prove important. The thiol serves as the site of thioester formation and its particular chemical attributes facihtate acyl transfer, carbon chain modification and condensation reactions. The phosphopantetheine thiol represents the most... 

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 remarkable efficiency of Shiina lactonization, which was mediated by acyl-transfer catalysts with MNBA, has been already demonstrated in a variety of successful total syntheses of natural products and biologically active compounds by other researchers (totaling over 370 citations to date). Furthermore, over 900 successful reactions using MNBA have been reported for the preparation of a variety of substrates including ester, amide, and lactone moieties. 

The reaction of benzylmagnesium chlorides wnth thiophenealde-hydes and thienyl ketones has been used for the preparation of styrylthiophenes and 1,2,2-triarylethylenes, which are of biological interest. In stilbene and 1,2,2-triphenylethylene the reactivity toward electrophilic reagents is transferred with deactivation to the double bond. However, styrylthiophene is formylated and acylated... 

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