Stereoselective Hydrolytic Reactions

In many cases, the stereoselectivity of the enzyme used in water and in an organic solvent is the same [16, 17] thus, complementary stereoisomers can be produced. If an enzyme prefers the R enantiomer of a chiral ester over the S ester, the R alcohol and the S ester can be obtained after a hydrolytic reaction. As the enzyme s stereochemical preference remains the same, transesterification in organic solvents will produce the S alcohol and R ester. 

Chemical transformations carried out by biological reagents such as purified enzyme preparations and by intact organisms such as fungi and bacteria have done much to ease the lot of the synthetic chemist in recent years. Regio- and stereoselective reactions such as C-hydroxylation (1, 2), S-oxidation (3, 4), carbonyl reduction (5, 6) and oxidation (7, 5), N- and O-dealkylation (9), N-oxidation (10), and hydrolytic reactions carried out by biological systems have been widely used in many areas of organic chemistry (11, 12). 

Lipases have been extensively used for the kinetic resolution of racemic alcohols or carboxylic acids in organic solvents. Chiral alcohols are usually reacted with achiral activated esters (such as vinyl, isopropenyh and trichloroethyl esters) for shifting the equilibrium to the desired products and avoiding problems of reversibility. For the same reasons, chiral acids are often resolved by using acidolysis of esters. In both cases, the overall stereoselectivity is affected by the thermodynamic activity of water of water favors hydrolytic reactions leading to a decrease in the optical purity of the desired ester. Direct esterifications are therefore difficult to apply since water formed during the reaction may increase the o of the system, favors reversibiUty, and diminishes the overall stereoselectivity. 

The enhancement of reaction rate as well as the stereoselectivity of hydrolytic reactions were studied by several authors [47]. Typical substrates were hydro-phobized activated esters of amino acids and typical catalysts were surface active peptides with histidine as active component. The kinetic resolution of racemic esters was determined. Brown [48] and Moss [49] gave explanations for the stereoselectivity. Ueoka et al. [50] reported one example where non-function-al amphiphiles as cosuxfactants can enormously improve the stereoselectivity the saponification of D,L-p-nitrophenyl J -dodecanoylphenylalaninate with the tripeptide Z-PheHisLeu-OH as catalyst in assemblies of ditetradecyldimethylam-monium bromide yielded practically pure L-M-dodecanoylphenylalanine upon the addition of between 7 to 20 mol % of the anionic surfactant sodium dodecyl sulfate (SDS). 

Stereoselective cis-dihydroxylation of the more hindered side of cycloalkenes is achieved with silver(I) or copper(II) acetates and iodine in wet acetic acid (Woodward gly-colization J.B. Siddall, 1966 L. Mangoni, 1973 R. Criegee, 1979) or with thallium(III) acetate via organothallium intermediates (E. Glotter, 1976). In these reactions the intermediate dioxolenium cation is supposed to be opened hydrolytically, not by Sn2 reaction. 

Access to the corresponding enantiopure hydroxy esters 133 and 134 of smaller fragments 2 with R =Me employed a highly stereoselective (ds>95%) Evans aldol reaction of allenic aldehydes 113 and rac-114 with boron enolate 124 followed by silylation to arrive at the y-trimethylsilyloxy allene substrates 125 and 126, respectively, for the crucial oxymercuration/methoxycarbonylation process (Scheme 19). Again, this operation provided the desired tetrahydrofurans 127 and 128 with excellent diastereoselectivity (dr=95 5). Chemoselective hydrolytic cleavage of the chiral auxiliary, chemoselective carboxylic acid reduction, and subsequent diastereoselective chelation-controlled enoate reduction (133 dr of crude product=80 20, 134 dr of crude product=84 16) eventually provided the pure stereoisomers 133 and 134 after preparative HPLC. 

As mentioned in part 2.1.3 hydrolytic enzymes are the most frequently used enzymes in organic chemistry. There are several reasons for this. Firstly, they are easy to ttse because they do not need cofactors like the oxidoreductases. Secondly, there are a large amormt of hydrolytic enzymes available because of their industrial interest. For instance detergent enzymes comprise proteases, celltrlases, amylases and lipases. Even if hydrolytic enzymes catalyse a chemically simple reaction, many important featirres of catalysis are still contained such as chemo-, regio- and stereoselectivity and specificity. 

Several triflates and metal salt hydrates were tested as Lewis acid catalysts (each 10 mol%) and the best results were obtained using Yb(OTf or Ni(C104)2-6H20. The stereoselective formation of bicyclic y-lactones (7) could be obtained from bicyclic nitronate (9) via the hydrolytic process by the action of a strong acid generated from Lewis acid with a small amount of water in both nitroalkene (5) and the Lewis acid. This new methodology of one-pot reaction also involves a new type of intramolecular HAD reaction of nitroalkenes as heterodienes, which provides stereochemically defined bicyclic nitronates. 

---