Enzymatic transformation, fluorinated

In fluorine-18 chemistry some enzymatic transformations of compounds already labelled with fluorine-18 have been reported the synthesis of 6-[ F] fluoro-L-DOPA from 4-[ F]catechol by jS-tyrosinase [241], the separation of racemic mixtures of p F]fluoroaromatic amino acids by L-amino acylase [242] and the preparation of the coenzyme uridine diphospho-2-deoxy-2-p F]fluoro-a-o-glucose from [ F]FDG-1-phosphate by UDP-glucose pyrophosphorylase [243]. In living nature compounds exhibiting a carbon-fluorine bond are very rare. 

Pseudosubstrates in which the fluorinated group is introduced to destabilize a reaction intermediate or a transition state of the enzymatic transformation. This can provoke inhibition or irreversible inactivation of the enzyme. 

A number of oxidation reactions of mono- and difluorosteroid compounds has been reported. In some reactions, the specific influence of a fluoro substituent on the reactivity has been observed the presence of a 9a-fluorine in a 11 /i-hydroxy-A4-3-oxo steroid causes completely stcreospecific alkaline epoxidation with hydrogen peroxide in a much slower reaction (4d vs 4 h) in comparison with the nonfluorinated analog.322 Most oxidations are accomplished by the highest selective biochemical (that is, by bacterial enzymatic) transformations. As the biochemical oxidation systems are not discussed in this section, only a list of selected transformations of steroids is presented in Table 21. For additional information see ref 323. 

P-Fluorine substituted amino acids are generally regarded as potential irreversible inhibitors of pyridoxal phosphate-dependent enzymes(89a,b-95). Fluorinated analogs are accepted by enzymes as substrates, as fluorine is comparable in steric demand to hydrogen, but often are not substrates for normal enzymatic transformation. 

Keywords Chiral fluorinated materials, microbial transformation, enzymatic optical resolution, microorganisms, stereochemistry. 

Asymmetric transformation of fluorine-containing ketones or esters into the corresponding optically active alcohols or acids by enzymes along with the discussion on the effect of fluorinated alkyl groups during the enzymatic optical resolution or diastereoselective reactions is described. 

Table IV contains selected examples of the enzymatic resolution of esters with various structures. As was discussed above, enhancement of the optical purity was possible by changing the acyl group or the enzyme (Run 1,2 or 6,7). Noteworthy is the fact that acetate 5 with a trifluoromethyl group was converted by lipase MY into the alcohol with (R) absolute configuration without exception in every case, when the stereochemistry has been determined. However, substrates with the other fluorine-containing substituents furnished alcohols whose asymmetric configuration depended on their structures. Particularly interesting is the relationship between Runs 4 and 5 (18), when resolution was accompanied with simultaneous separation of diastereomers. To the best of our knowledge, this is the first example of the type of resolution of both diastereomers and enantiomers by enzymatic hydrolysis in a single transformation.

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