Biological Acylation Reactions

The discussion of acylation reactions in this chapter is focused on fluonnated carboxylic acid derivatives and their use to build up new fluorine-containing molecules of a general preparative interest Fifteen years ago, fluonnated carboxylic acids and their derivatives were used mainly for technical applications [/] Since then, an ever growing interest for selectively fluonnated molecules for biological applications [2, 3, 4, 5] has challenged many chemists to use bulk chemicals such as tnfluoroacetic acid and chlorodifluoroacetic acid as starting materials for the solution of the inherent synthetic problems [d, 7,, 9]... 

The asymmetric acylation reaction has proven utility in the synthesis of biologically relevant targets. This is demonstrated by the plethora of applications of lipases and esterases in total syntheses [ 1 ]. While these enzymes often display superb selectivities, their application to a broad class of substrates may be difficult and unpredictable [2]. To increase access to these materials in optically pure form, over the past decade several groups have developed small molecule catalysts for the asymmetric acylation reaction [3,4], In addition, these catalysts... 

Foreign carboxylic acids and amines undergo biological acylation to form amide conjugates. Acylation reactions are of two types. The first involves an activated conjugating intermediate, acetyl CoA, and the xenobiotic. The reaction is referred to as acetylation. 

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). 

Many of the more recent applications of intramolecular Friedel-Crafts acylation reactions have involved the synthesis of biologically active tetracycline derivatives. In the synthesis of aclacinomycin- the acid shown in equation (42) was cyclized efficiently to the anthrone using trifluoroacetic anhydride in dichloromethane and then converted immediately into the anthraquinone shown. 

The versatility of this approach is illustrated by the synthesis of polyunsaturated fatty acids of special interest. Ostopanic acid, a cytotoxic fatty acid, is directly obtained by acylation reactions with the appropriate acyl chlorides, whereas /3-parinaric acid methyl ester, an interesting fiuorescent probe for biological membranes, is prepared by a selective double acylation, followed by reduction and dehydration reactions (eq 2). ... 

Keto-4-arylbutanoic acid derivatives resulting from Friedel-Crafts acylation reaction are prepared in high yields and purity using AICI3. Such compounds are useful structural moieties in the synthesis of several biologically active compounds such as Fenbufen, a nonsteroidal anti-inflammatory drug (eq 48). 4... 

At molecular level, the manifestations of the biological activity appear in specific biochemical reactions, conformational behavior, and dynamical properties of biomolecules. Experimental studies of various partially hydrated enzymatic proteins show that their activity accelerates rapidly at some critical hydration levels. Onset of the enzymatic activity of urease occurs at 0.15 g/g [469]. In the presence of chymotrypsin, the acylation reaction is undetectable at hydrations /i< 0.12 g/g, but its rate grows sharply above this critical hydration level [470]. The rate of enzymatic activity of glucose-6-phosphate dehydrogenase, hexoki-nase, and fumarase becomes detectable and start to increase sharply at hK 0.20 g/g, whereas this critical hydration is about 0.15 g/g for phosphoglucose isomerase [471]. Enzymatic activity of lysozyme can be detected only when hydration level achieves h 0.20 g/g [472, 473] (see Fig. 92). 

Once formed cholesterol undergoes a number of biochemical transformations A very common one is acylation of its C 3 hydroxyl group by reaction with coenzyme A derivatives of fatty acids Other processes convert cholesterol to the biologically impor tant steroids described m the following sections... 

A -l,3,4-Oxadiazoline-5-thione, 2-phenyl-alkylation, 6, 440 Oxadiazolinethiones acylation, 6, 432 Mannich reaction, 6, 431 pK 6, 435 ring cleavage, 6, 433 Oxadiazoline-5-thiones acidity, 6, 435 stability, 6, 431 A -Oxadiazoline-5-thiones biological activity, 6, 445 synthesis, 6, 441 A -1,3,4-Oxadiazoline-5-thiones... 

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