Racemic compounds absolute configuration determination

The presence of asymmetric C atoms in a molecule may, of course, be indicated by diastereotopic shifts and absolute configurations may, as already shown, be determined empirically by comparison of diastereotopic shifts However, enantiomers are not differentiated in the NMR spectrum. The spectrum gives no indication as to whether a chiral compound exists in a racemic form or as a pure enantiomer. 

Selenurane oxides are also one of the hypervalent selenium compounds. Recently, the enantiomers of chiral selenurane oxide 38 were isolated for the first time by enantioselective liquid chromatography of the racemate or by spontaneous resolution occurring during slow evaporation of its acetonitrile solution or slow crystallization from the same solvent.57 The absolute configurations of the enantiomers were determined by X-ray crystallographic analysis (Scheme 17). 

Shihunine (57), previously isolated from Dendrobium lohohense Tang and Wang (99, 100) andD. pierardii Roxb. (Orchidaceae) (101), has been found as a racemate in Banisteriopsis caapi Morton (102). This plant species also contained the optically active dihydroshihunine 58, a compound only known before as a racemic synthetic material. Both 57 and 58 were identified by direct comparison with authentic samples. The absolute configuration of (+)-(58) was determined as 25 by comparison of the CD spectra of 58 and of the a-phenylethylamines (102). 

Since all of the thiol addition products were unknown compounds, except for racemic 3-phenylthiocyclohexanone, it became necessary to devise a method far determining the absolute configuration without resorting to Bijvoet s method (53) for each new compound (see Table 4). This was accomplished by preparing the thioacetal of the adamantanedione, a model 3-thiosubstituted cyclohexanone of known absolute configuration (54) (eq. [10]). 

Organosulfur chemistry is presently a particularly dynamic subject area. The stereochemical aspects of this field are surveyed by M. Mikojajczyk and J. Drabowicz. in the fifth chapter, entitled Qural Organosulfur Compounds. The synthesis, resolution, and application of a wide range of chiral sulfur compounds are described as are the determination of absolute configuration and of enantiomeric purity of these substances. A discussion of the dynamic stereochemistry of chiral sulfur compounds including racemization processes follows. Finally, nucleophilic substitution on and reaction of such compounds with electrophiles, their use in asymmetric synthesis, and asymmetric induction in the transfer of chirality from sulfur to other centers is discussed in a chapter that should be of interest to chemists in several disciplines, in particular synthetic and natural product chemistry. 

Ondansetron (17) is a racemic compound not easy to resolve by chemical means because the carbonyl function is poorly reactive so it is difficult to form chiral derivatives. However, a resolution was achieved by the classical method of forming diastereomeric salts with an optically active acid and then separating the salts by recrystallisation. A number of acids were tried, but only the salts prepared from (-f)- and (—)-di-p-toluoyltartaric acid could be separated in this way. Each isomer was obtained in greater than 95 %ee. The absolute stereochemistry of the isomer from the (-E)-acid was determined by X-ray crystallography (Williams, D., personal communication) and shown to possess the 5-configuration (18). 

As described in the section dealing with liquid chromatographic methods, the reaction of 0,0-di-substituted tartaric anhydrides with racemic amino alcohols in acidic solution leads exclusively to the corresponding diastereomeric monoesters, which are easily separated by reversed-phase HPLC. However, H- and sometimes 13C-NMR spectra of these compounds are in many cases also highly useful for determining the diastereomeric ratio and in many cases the absolute configuration. 

In cases where racemic mixtures of compounds with more than one of chiral unit and with known relative configuration are resolved, it is sufficient, in principle, to determine the absolute configuration at one of the chiral units for one of the pure enantiomers in order to establish full configurational assignment. 

Related to this is the use of amino acid derived reagents for resolution of racemic carbonyl compounds and determination of absolute configurations by X-ray analysis at the imine stage. This is exemplified by the L-valinol derived imine of tricarboxyl (l-formyl-2-methoxyphenyl) chromium (see p 417)88. 

Neonepetalactone, 61 (Fig. 1.2.3), a bioactive compound found to be quite attractive to cats [41], was isolated in 1965 from the leaves and galls of Actinidia polygama by T. Sakan et al. and its absolute configuration was determined in 1980 [41b]. As some syntheses of the racemic mixture or ex-chiral-pool syntheses had already been reported, we realized that our SAMP/RAMP hydrazone methodology would make it possible to develop a very short asymmetric synthesis of this bioactive 8-lactone. 

Compounds that contain an asymmetric substitutions on a carbon atoms exist in enantiomorphic forms. These differ only in the direction of rotation of polarized light. When the absolute configuration has been identified in the original report, these compounds are identified by (R)- and (S)- prefixes. Sometimes prefixes such as d-, /-, (+)-, and (-)-, which are given in the original report have been used. Very often no identification of the optical isomer is given even when the compound contains an asymmetric carbon atom Then it is assumed that the samples are racemic mixtures. However, none of these distinctions affect the densities of liquids, therefore all the isomers of this type are combined to determined the recommended values. If a compound contains more than one asymmetric carbon atom diasteieomers can exist. In principle, these might have different densities, but no examples have been found. 

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