Regioselective hydrolysis diesters

Regioselective hydrolysis of diesters is a challenging problem ia synthetic chemistry because the side reactions always reduce the yield of desired product. Some Upases are well suited to perform this task. Lipase OF-360 (Meito Sangyo) hydrolyzes diester (55) ia 74% theoretical yield and 93% ee (70). Lipase from Pseudomonas cepacia suspended ia diisopropyl ether saturated with water hydrolyzes triester (56) with a remarkable efficiency and regio- and stereoselectivity (71). 

Regioselective hydrolysis of the diester 27 gave the 1,3-thiazetidine 28 where the thiazetidine ring is fused to a quinolone nucleus <99CPB1765>. Derivatives of the tricyclic system, e.g. 29, showed activity against gram-positive bacteria including quinolone-resistant MRS A <99H(51)2915>. 

A full paper containing all these data (previously published as short communications), as well as some mechanistic proposals concerning the regioselective hydrolysis of the diesters and the unexpected formation under certain conditions of the products not related to the cycloadditions, was published later [88]. 

The chemistry of complex lipids is dominated by regioselective hydrolysis reactions of (1) the glyceryl fatty acid esters and (2) phosphate diesters. Both types of reactions are routinely performed with the corresponding esterases. A large variety of lipid active transferase enzymes is also commercially available. Phospholipases Aj, A, C, and D, for example, split any of the four ester bonds of a phospholipid regioselectively. The product without a fatty acid side chain at C2 of glycerol is called a lysophospholipid. Lecithin-cholesterol-acyltransferase transfers the fatty acid at C2, often linoleic acid, to the OH group at C3 of cho-... 

Scheme 2.24 Regioselective hydrolysis of /Z-diastereotopic diesters by porcine liver esterase...

Figure 18 The regioselective hydrolysis of the diesters of ( )-2-substituted-2-butene-l,4-diols.

Ortho-substituted phenolic diesters, such as bis-p-(l,4-butyroyl)-2-octylhydro-quinone (Figure 12.9), can be hydrolyzed in the more hindered 1-position or in the less-hindered 4-position. The regioselectivity of hydrolysis to the monoester, as expressed by the ratio of kcM/Ku values, depends approximately linearly on log P over the range from acetonitrile (log P -0.33) to cyclohexane (log P 3.2), and is thus controlled by the hydrophobicity of the solvent (Rubio, 1991). 

The cadmium 4,5-dioxo-4,5-seco-pheophorbidate 14 was reduced with sodium borohydride and demetallated with dilute aqueous acid to provide methyl-4,5-dioxo-4,5-secopheophorbidate 16 in about 72% yield. The UV/Vis-spectrum of the weakly fluorescing red diester 16 has prominent absorbance maxima near 500 and 316nm (1). The diester 16 was spectroscopically identified (76) with the methylation product (compound 32a, see Scheme 16) of the diacid 9 from the green alga C. protothecoides (78). Regioselective, partial hydrolysis of the diester 16 with pig liver esterase occurred practically exclusively at the propionic acid side chain and produced the red chlorophyll catabolite 11 (RCC,... 

Proteases such as a-chymotrypsin, papain, and subtilisin are also useful for regioselective hydrolytic transformations (Scheme 2.40). For example, while regio-selective hydrolysis of a dehydroglutamate diester at the 1-position can be achieved using a-chymotrypsin, the 5-ester is attacked by the protease papain [260]. It is noteworthy that papain is one of the few enzymes used for organic synthetic transformations which originate from plant sources (papaya). Other related protease preparations are derived from fig (ficin) and pineapple stem (bromelain) [261]. 

Regioselectivity" is another useful property displayed by many enzymes. This refers to the transformation of one functional group while leaving other identical (or nearly identical) moieties at different locations within the molecule untouched. For example, among three esters in a triacylglyeride many lipases hydrolyze only one position, and do not catalyze further hydrolysis of the diester produrt. 

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