Vicinal diol resolution

Enantiopure epoxides and vicinal diols are important versatile chiral building blocks for pharmaceuticals (Hanson, 1991). Their preparation has much in common and they may also be converted into one another. These chirons may be obtained both by asymmetric synthesis and resolution of racemic mixtures. When planning a synthetic strategy both enzymic and non-enzymic methods have to be taken into account. In recent years there has been considerable advance in non-enzymic methods as mentioned in part 2.1.1. Formation of epoxides and vicinal diols from aromatics is important for the break down of benzene compounds in nature (See part 2.6.5). 

The bioeatalytie resolution of epoxides has mainly been performed in single aqueous buffer systems. In our laboratory, B/nEH has been proved to be very useful for ehiral synthesis of (i )-GPE on a preparative scale. More importantly, this enzyme exhibited a eomplementary enantiospecificity as compared with those deseribed so far, affording the unreacted epoxide in (S)-configuration which is the solely useful enantiomer for synthesis of bioactive p-blockers. In a single aqueous phase, however, most epoxides including GPE may be spontaneously hydrolyzed into vicinal diols without any enantiospecificity. In addition, only at a very low concentration can epoxides be dissolved in aqueous media. The instability and low solubility of epoxides in the aqueous phase may result in a remarkable decrease in the yield of kinetic resolutions, thus limiting the application of these resolution processes on a practical scale. 

In order to circumvent the disadvantages of kinetic resolution, several protocols were developed towards the enantioconvergent hydrolysis of epoxides, which lead to a single enantiomeric vicinal diol as the sole product from the racemate. 

In addition, antipodes of racemic 2-hydroxyaldehydes 50 tvith a (2R)-hydroxyl group are discriminated tvith complete enantioselectivity this enables efficient kinetic resolution (Figure 5.53) [260, 261]. Vicinal diols of (3S,4R) configuration are thereby generated tvith high stereocontrol. This... 

Epoxide hydrolases (EH) are promising biocatalysts for the preparation of chiral epoxides and vicinal diols and can be effectively used in the resolution of racemic epoxides. There are number of reviews published on the synthetic application of epoxide hydrolase and preparation of chiral epoxides [52-57] and additional information can be found elsewhere in this book. 

Disubstituted aliphatic oxiranes have been reported to be hydrolyzed by EHs from fungi [131], yeast, and bacteria. The most interesting results were observed with yeast and bacterial EHs. As far as kinetic resolution is concerned, it was shown by Weijers [116] that R. glutinis catalyzed the enantioselective hydrolysis of cis-2,3- and trans-2,3-epoxypentane, resulting in residual (2R)-epoxides with yields that approached the theoretical maximum of 50%. More interestingly, biocatalytic transformations of racemic 2,3-disubstituted oxiranes to vicinal diols with high ees at... 

Diastereoisomeric acetal formation catalyzed by KIO has been applied to the resolution of racemic ketones, with diethyl (+)-(/ ,/f)-tartrate as an optically active vicinal diol. ... 

TLC offers a number of advantages over column chromatography. It is more rapid and sensitive, gives better resolution and is usually much quicker. Moreover, the apparatus required is minimal and, especially if plates are made in the laboratory, the technique is inexpensive. By incorporating various chemicals into the thin layer, special lipid separations can be made. For example, silver nitrate allows fatty acids (or more complex lipids) to be separated on the basis of their unsaturation. Silicone oil-silica gel TLC works on the basis of reverse-phase separation and can be used to fractionate fatty acid mixtures based on their hydrophobicity, with shorter chain or unsaturated components migrating faster. Boric acid impregnation allows separation of threo- or erythro- isomers of vicinal diols or fractionation of molecular species of ceramides. 

The remaining unreacted (RJ-20 can be trapped with an aldehyde such as pivalaldehyde giving the chiral homopro-pargylic alcohol in 87.5% ee.74 This kinetic resolution has been used to prepare anti/inti-vicinal amino diols in > 95% ee and dr > 40 l.75 In general, diorganozincs are more easily prepared in optically pure form. On another hand, secondary zinc reagents prepared by the direct zinc insertion to secondary alkyl iodides are obtained without stereoselectivity (Scheme 4).76... 

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