Biocatalytic hydroxylations

The important metaboUsm of the neurotransmitters norepinephrine, epinephrine, dopa, and serotonin involves pterin-dependent monooxygenases. The direct biocatalytic hydroxylation of the aromatic amino acids phenylalanine, tyrosine, and tryptophane requires tetrahydrobiopterin and Fe as the cofactors [60]. The cleavage of unsaturated glyceryl ethers by glyceryl ether monooxygenase also requires tetrahydrobioterin as the cofactor [61]. 

The vast majority of enzyme-catalyzed stereoselective hydroxylations are carried out by the cytochrome P450-dependent monoxygenases [4]. The membrane-bound nature of the majority of these enzymes, together with their functional dependence on the presence of cofactors and their related electron transport proteins, has ensured that preparative biocatalytic hydroxylations are most usefully performed with whole-cell catalysts. The exceptions to this generality, the lipoxygenases and haloperoxidases, will be considered in Sec. n.B. 

Various biocatalytic options have been presented for the desymmetrization of meso-diols to chiral hydroxyl-ketones. A particularly facile system is represented by... 

Fessner, W.-D. and Helaine, V. (2001) Biocatalytic synthesis of hydroxylated natural products using aldolases and related enzymes. Current Opinion in Biotechnology, 12, 574-586. 

Regioselective esterification of the 8-hydroxyl group of accumulated monacolin J, produced using a truncated lovastatin biosynthetic pathway, could provide a viable biocatalytic route to simvastatin. With this aim, Xie and Tang cloned and expressed the acyl transferase LovD from the lovastatin biosynthetic pathway into E. colv, they found... 

Enzymatic hydroxylation activation has perhaps the highest potential of all enzyme-catalyzed transformations for synthetic applications. Currently, whole-cell processes are used and the outcomes are often unpredictable. The discovery of new oxygenases and efficient hosts for protein expression remain keys to further expanding the synthetic applications of biocatalytic C—H activation [89, 90]. 

W Adam, W Boland, J Hartmann-Schreier, H-U Humpf, M Lazarus, A Saffert, CR Saha-Moller, P Schreier. a Hydroxylation of carboxylic acids with molecular oxygen catalyzed by the a oxidase of peas (Pisum sativum) a novel biocatalytic synthesis of enantiomerically pure (R)-2-hydroxy acids. J Am Chem Soc 120 11044— 11048, 1998. 

Lipases are of remarkable practical interest since they have been used in numerous biocatalytic applications, such as kinetic resolution of alcohols and carboxyl esters (both in water and in non-aqueous media) [1], regioselective acylations of poly-hydroxylated compounds, and the preparation of enantiopure amino acids and amides [2, 3]. Moreover, lipases are stable in organic solvents, do not require cofactors, possess broad substrate specificity, and exhibit, in general, a high enantioselectivity. All these features have contributed to make hpases the class of enzyme with the highest number of biocatalytic applications carried out in neat organic solvents. 

In recent years biotransformations have also shown their potential when applied to nucleoside chemistry [7]. This chapter will give several examples that cover the different possibiUties using biocatalysts, especially lipases, in order to synthesize new nucleoside analogs. The chapter will demonstrate some applications of enzymatic acylations and alkoxycarbonylations for the synthesis of new analogs. The utQity of these biocatalytic reactions for selective transformations in nucleosides is noteworthy. In addition, some of these biocatalytic processes can be used not only for protection or activation of hydroxyl groups, but also for enzymatic resolution of racemic mixtures of nucleosides. Moreover, some possibilities with other biocatalysts that can modify bases, such as deaminases [8] or enzymes that catalyze the synthesis of new nucleoside analogs via transglycosylation [9] are also discussed. 

GlyC can be synthesized following a two-step biocatalytic process (Scheme 9.8). In the first step, one of two primary hydroxyl groups of... 

An exceptional case for an enantioconvergent biocatalytic hydrolysis of a ( )-c -2,3-epoxyalkane is shown in Scheme 2.97 [617]. Based on O-labeling experiments, the stereochemical pathway of this reaction was elucidated to proceed via attack of the (formal) hydroxyl ion at the (S)-configured oxirane carbon atom with concomitant inversion of configuration at both enantiomers with opposite regioselectivity. As a result, the (/ ,/ )-diol was formed as the sole product in up to 97% e.e. in almost quantitative yield. 

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