Diastereoisomer separation

After the preparation of diastereoisomers by introduction of an optically active resolving agent, the next problem in an optical resolution is to separate the diastereoisomers. It should be recalled that the components of a pair of diastereoisomers necessarily have very similar properties. They contain exactly the same ligands and differ only in their arrangement around the metal atom. Several separation techniques have been used, based either on the fact that diastereoisomers differ in solubility, or in retention time during chromatography. 

As described later, diastereoisomers sometimes interconvert at room temperature, or even below. Then, by milking the equilibrium by slow crystallization, it is often possible to convert all of the material into a single isomer which is usually configurationally stable in the solid state (51, 63). 

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The reaction of dihydropyran with water in the presence of a trace of mineral acid gives an equilibrium mixture of 2-hydroxytetrahydropyran and 5-hydroxypentanal. However, the products from the addition of alcohols to dihydropyrans are stable under basic conditions and can be isolated after destruction of the acid catalyst (47JA2246). A wide range of substituted tetrahydropyrans has been made in this way and the diastereoisomers separated by gas chromatography (68JOC3754). 

All of the optically active compounds prepared by diastereoisomer separation and/or conversion to enantiomers have proved to be configurationally stable at the metal center as long as they are in the solid state. Concerning their behavior in solution, however, the optically active or-gano-transition-metal compounds are divided into two groups (a) compounds configurationally stable at the metal center, which do not racem-ize or epimerize with respect to the metal atom prior to decomposition and (b) compounds configurationally labile at the metal center which racemize or epimerize with respect to the metal atom prior to decomposition. 

The product, mixed with charcoal, is filtered off and washed with 40% ethanol (60 ml.), the washings being discarded. The diastereoisomer is then extracted from the charcoal with successive portions of hot water (60°). The final wash portion should be colorless, and usually 300 ml. will suffice. The extract is evaporated to a volume of 50 ml., and on cooling in ice the pure diastereoisomer separates as orange-yellow crystals, [a]D = +103° the yield is 40 to 41 g. or 78 to 82% on the assumption of complete conversion to one isomer. Conversion to the iodide [a]D = +91° is effected as in the previous synthesis. The yield is 43 to 44 g. or 60 to 65%. 

If we now hydrolyse each diastereoisomer separately, we have done something rather remarkable we have managed to separate to two enantiomers of the starting alcohol. 

If the chiral auxiliary used for the formation of diastereoisomers is covalently attached to the ferrocene derivative, other techniques such as chromatography may be applied for diastereoisomer separation. 1-Phenylethylamine is a comparatively... 

The enriched fractions are passed once more through the same colunms using the same solvent mixture, affording another 0.85 g of each isomer in pure form. The yield from 5 g of crude 1.2.1c is thus about 1.6 g of each diastereoisomer (separation of 64% of the total). 

HBCD. However, until now the different isomers have not been separated by this technique. Moreover, and because isomers of HBCD are thermally labile (it is known that HBCD decomposition takes place between 240 and 270 C), elution from a GC column usually results in a broad and diffuse peak. In addition, a number of chromatographic peaks corresponding to different breakdown products were detected. These peaks could interfere with some BFR congeners, such as BDE-99 [65]. To solve these analytical difficulties, recent investigations were made using LC approaches. Actually, LC-MS and LC-tandem MS (MS-MS) are the best methods for measuring HBCD diastereoisomers separately in environmental samples [66,67]. Chromatographic columns such as C18 were used in the majority of HBCD-isomers studies. 

TLC is commonly used for the separation of different classes of wax components or for analysis of monomers from cutin and suberin depolymerization. A typical separation is shown in Fig. 6.12. By such methods, it is possible to separate hydrocarbons, wax esters, primary alcohols, secondary alcohols and /8-diketones from plant waxes (von Wettstein-Knowles, 1979). Products of hydrogenolysis from cutin can be separated by TLC into alkan-l-ols, alkane-a,ft>-diols, Cis triols, Ci6 triols and Cis tetrols (Kolattukudy, 1980). Unsaturated components can be resolved by argentation-TLC (Tulloch, 1976) and threo or erythro diastereoisomers separated by boric acid/silica gel TLC (Eglinton and Hunneman, 1968). Straight-chain compounds can be preferentially removed from branched compounds as their urea complexes (Kolattukudy, 1980). 

Hereinafter, the possibilities of enantiomer and diastereoisomer separations based on crystallization are shown by known examples. 

Chiral column Isomers/enantiomer pairs/diastereoisomer Separation pairs conditions Results ... 

The comprehensive chiral HPLC method development approach designed for brivanib alaninate enantiomers and diastereoisomers separation included [150] the following ... 

The chemical method of resolving racemates consists of a sequence of reactions which is general in organic chemistry the formation of dias-tereo-isomers by the reaction of the racemate with some optically active compound, subsequent separation of these by crystallization or chromatography and, finally, the removal from each of the diastereoisomers separated of the optically active residue initially introduced, with the formation of the individual enantiomers. In the resolution of racemic steroids... 

This last compound is a mixture of diastereoisomers separable by HPLC (Edmonds, 2000). With 40 ppm of arsenic (per fresh weight), the species Sargassum lacerifo-lium is the alga that accumulates this element the most (Francesconi et al, 1991). Some 30 arsenate derivatives isolated either from brown algae, or from the invertebrates that consume them, are currently known and their biosyntheses derived from biomethylation of sedimentary arsenates via S-adenosyl-methionine (Figure 14.18). 

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