Diastereoisomers chromatographic separation

The major sulfinamide diastereoisoraer (56) was obtained diastereoisomerically pure in 74% yield after crystallization (initial diastereoisomer ratio 90 10). Subsequent desulfurization, benzoylation, and stereoselective enolate hydroxylation (Scheme 4.30) gave an 86 14, syn anti mixture of the target diastereoisomers. Chromatographic separation of the product diastereoisomers afforded (2i ,3S)-(-)-(57), the methyl ester of the taxol C,j side chain, in 49% yield and > 93% ee. 

P-chiral dibenzophosphole oxide (52a) (Scheme 14) shows liquid crystalline behaviour [52], a property that is of interest in the area of electro-optical displays [53]. Chiral resolution of (52a) was achieved by column chromatographic separation of the diastereoisomers obtained following coordination of the o -benzophosphole (52b) to chiral cyclometallated palladium(II) complexes [52]. Notably, the presence of a stereogenic P-centre is sufficient to generate a chiral cholesteric phase. 

The use of sulfoximines in the syntheses of optically active compounds has been reported [429]. A remarkable ketone methylcnation with optical resolution was realized. A highly selective diastereofacial addition of an enantiopure sulfoximine to a racemic ketone, chromatographic separation of the two diastereoisomers and reductive cleavage yielded both enantiomers of p-panasinsene [430], isolated from the root of ginseng, a herb used in Chinese folk medicine. 

Figure 7.14 Chromatographic separation of diastereoisomers quinine and quinidine stationary phase (S) naphthylurea 250 x 4.6 mm ID. Chromatographic conditions C02 methanol, 0.1 Vo, TEA (80 20), 3 ml/ min, 50°C, 12.5 MPa, and X = 230 nm. (Reprinted from Ref. 17 with kind permission of Wiley-Liss, Inc. New York.)...

The optical resolution of racemates 22a, 25a, and 27a was carried out by chromatographic separation of their (4/ ,5S)-MPOT-amide derivatives 22b, 25b, and 27b. The absolute stereochemistry of each pure diastereoisomer was confirmed by comparing the physical data of its derivative with those of the authentic compound in each case. Thus, (4i ,5S)-MPOT (5) proved to be a satisfactory chiral reagent useful for analytical separation and optical resolution of racemic carboxylic acids and amino acids (85JCS(P1)2361). 

Thus, iV-ethylpiperidine was added to a suspension of tin(II) trifluoromethanesulfonate in anhydrous CH2CI2 at — 50°C under Ar, After addition of a solution of 3-acetyl-(4/ ,5S)-MPOT (30) in CH2CI2, the mixture was stirred at — 50 to — 40°C for 3 hr. A solution of isobutyraldehyde in CH2CI2 was then added at - 78°C and the mixture was stirred at the same temperature for 20 min. Usual workup of the reaction mixture gave a mixture of diastereoisomers 32 and 33, the ratio of which was readily checked by HPLC equipped with a UV detector. Chromatographic separation of each diastereoisomer gave optically pure 32 and 33 (Scheme 5). 

Isonupharamine (XLI) was converted to deoxynupharidine which was a mixture of diastereoisomers—(XLII) and (XLIII)—differing in configuration at C-7. After chromatographic separation on alumina the form XLII was shown to be identical with natural deoxynupharidine, i.e., le,7a-dimethyl-4e-[3-furyl]-quinolizidine. 

Figure 34-20 Chromatographic separation of amphetamine and methamphetamine stereoisomers after their reaction with R(-)-a-methoxy-a-trifluoromethyl-phenylacetyl chloride to form corresponding diastereoisomers. (—)-Amp and (+)-Amp, R(-)-, and S(-t)-amphetamine, respectively. (-)-Mamp and (+)-Mamp, R(-)-, and S(-t)-methamphetamlne, respectively.This urine specimen is from an individual believed to have ingested racemic methamphetamine.

Numerous racemates have been separated into their enantiomers since the first success in 1848 by Pasteur. The traditional method is to derivatize a racemate into a mixture of two diastereoisomers by means of so-called resolving agents, and then to separate the diastereoisomers by recrystallization or chromatography. Recent development of chiral stationary phases for chromatographic separation of the enantiomers made it possible to separate them even without derivatization. Another method of choice is to use enzymes for enantiomer separation. Examples in this chapter will illustrate the use of these methods. After enantiomer separation, the absolute configuration and the enantiomeric purity of the resulting enantiomers must be determined. 

Following this exploratory work, the Schmidt group (13) reported the first homochiral synthesis of methyl (-)- and (+)-nonactate using (S)-propylene oxide as the only enantiomerically pure starting material (Scheme 4). This gave the mixture of diastereoisomeric methyl nonactates 38, 39,40 and 41, all with the ( -configuration at C-8, and chromatographic separation provided 25% of the natural (-) ester 38. The mixture of the other three diastereoisomers (39+40+41) was converted by Walden inversion into a mixture of the same three compounds with C-8 inverted, from which (+)-methyl (25,35,6R,8/J)-nonactate 44 could be isolated in approximately the same amount as its enantiomer 38. 

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