Centre of asymmetry

An E-Z discrimination between isomeric oxaziridines (27) was made by NMR data (69JCS(C)2650). The methyl groups of the isopropyl side chains in the compounds (27) are nonequivalent due to the neighboring carbon and nitrogen centres of asymmetry and possibly due to restricted rotation around the exocyclic C—N bond in the case of the Z isomer. The chemical shift of a methyl group in (Z)-(27) appears at extraordinarily high field, an effect probably due to the anisotropic effect of the p-nitrophenyl group in the isomer believed to be Z. 

Also due to the high barrier of inversion, optically active oxaziridines are stable and were prepared repeatedly. To avoid additional centres of asymmetry in the molecule, symmetrical ketones were used as starting materials and converted to oxaziridines by optically active peroxyacids via their ketimines (69CC1086, 69JCS(C)2648). In optically active oxaziridines, made from benzophenone, cyclohexanone and adamantanone, the order of magnitude of the inversion barriers was determined by racemization experiments and was found to be identical with former results of NMR study. Inversion barriers of 128-132 kJ moF were found in the A-isopropyl compounds of the ketones mentioned inversion barriers of the A-t-butyl compounds lie markedly lower (104-110 kJ moF ). Thus, the A-t-butyloxaziridine derived from adamantanone loses half of its chirality within 2.3 days at 20 C (73JCS(P2)1575). 

It is considered that in these new forms racemisation or reversible inversion has occurred at the centre of asymmetry in the phthalide group, and that the centre of asymmetry in the isoquinoline nucleus is unaffected. The melting-point, 176°, of each new isomeride is depressed by addition of the corresponding a-narcotine and the specific rotation of l-j3-narcotine, W548 is 101° (CHCI3) or — 59-2° (N. HCl), that of i-a-narcotine, under the same conditions being — 246° and -f 50-4° respectively. 

Phaeanthine, C3JH42O0N2. (Item 8 list, p. 350.) This alkaloid was isolated by Santos.It has m.p. 210°, [a]u°° — 278° (CHCI3), yields a hydriodide, m.p. 268°, picrate, m.p. 263°, aurichloride, m.p. 170-1°, and a platinichloride, m.p. 280° (dec.), and contains four methoxyl and two methylimino groups. By the Hofmann degradation process it yields an optically inactive methine base A, m.p. 173°, which is oxidised by potassium permanganate in acetone to 2-methoxy-5 4 -dicarboxydiphenyl ether (p. 348). A comparison of the properties of phseanthine and tetrandrine by Kondo and Keimatsu indicates that these two alkaloids are optical antipodes, so that phseanthine will be represented by either (XXXIX) or (XL) as given on p. 348, 1 and of these two formula (R = Me) one must represent oxyacanthine methyl ether and the other berbamine methyl ether (centres of asymmetry d- and 1-) tetrandrine (centres of asymmetry both d-) and phseanthine (centres of asymmetry both 1-). 

The relationship of psychotrinc and 0-methylpsychotrine to the two pairs of stereoisomerides a) cephaeline -j- tsocephaeline, and (b) emetine + isoemetine respectively, implies that in each of these reductions one ethylenic linkage is saturated and produces one new centre of asymmetry. This ethylenic linkage is assumed to he at to C , so that on this basis the components of each of the stereoisomeric pairs a) and (b) just referred to must he epimeric pairs about C. ... 

Using the (— )-Aowocincholoipon produced as described, Rabe and Schultze, by the same sequence of reactions, have produced (—)-dihydro-quininone (m.p. 98-9[a]f, ° — 70-0° (final value EtOH)), which on hydrogenation in presence of palladium gave a mixture of bases, of which (—)-dihydroquinidine and (-j-)-dihydroquinine were isolated. The characters of these mirror-image isomerides of dihydroquinidine and dihydroquinine respectively have been given already with the directions of rotation at the centres of asymmetry C , C , C , C (see table, p. 446). 

The occurrence of two optically active forms of each of the acids, lysergic and wolysergic, implies the existence in each of one centre of asymmetry (C ). 

The carboxjJ group, and therefore the centre of asymmetry, was first placed at C , but of the four possible positions that at C is now considered... 

Chondrodendron polyanthum, 371 Chondrodendron tomentosum, 363, 371, 373, 377, 391 alkaloids, 376 Chondrodine, 363, 364 Chondrofoline, 364, 365 Chrycentrine, 172, 313 Chiysanthemine, 773 Chrysanthemum cineraricefoHum, 773 Chuchuara, 781 Chuehuhuasha, 781 Cicuta virosa, 13 Cinchamidine, 419, 429 Cinchene, 439 Cinchenine, 438, 439, 440 apoCinchenine, 440, 441 Cincholoipon, 438 Cincholoiponic acid, 438, 443 Cinchomeronic acid, 183 Cinchona alkaloid structure, synthesis, 457 Cinchona alkaloids, bactericidal action of some derivatives, 478 centres of asymmetry, 445 constitution, 435 formulae and characters of transformation products, 449, 451 general formula, 443 hydroxydihydro-bases, 448, 452-4 melting-points and specific rotations, 446... 

Even metals like Cu, Pt, or Pd which form tetrahedral coordination compounds also from asymmetric compounds. In all these cases, therefore, the centre of asymmetry has a tetrahedral configuration just like an asymmetric carbon atom. 

Isomerism due to Asymmetric Cobalt Atoms.—Werner established his formulas for the cobalt-ammines by proving the fact suggested by his theory that certain of the cobalt atoms in the ammines were centres of asymmetry, and therefore optical activity should be possible. Having established this for some of the simple cobalt-ammines, he then showed that in many of the polynuclear compounds optical activity exists. Thus he prepared optically active isomers of tetraethylenedianaino-... 

It is clear that the stereochemistry of the phosphorane is subordinated to the 70 70a equilibrium resulting in an interconversion between x and x, and therefore in the automatic racemization of the structure. The same reasoning applies to homologues of 70 obtained by substitution on the C atoms of either ring, even if this substitution produces new centres of asymmetry besides that on the central P atom. 

If a pure compound containing a centre of asymmetry is chromatographed on a chiral stationary phase, two peaks corresponding to the R and S enantiomers will be observed and the area will be proportional to the abundance of each of the forms. The optical purity, defined in terms of enantiomeric excess (e.e.), can be obtained using the equation below where AR and As represent the areas of the peaks for each enantiomer ... 

The tocotrienols possess one centre of asymmetry, at C-2, in addition to the sites of geometrical isomerism at C-3 and C-7. The equivalent natural tocotrienols to the tocopherols mentioned above have a (IKyi -trans-T-trans configuration [44-47]. Indeed, all natural tocopherols and tocotrienols have the R configuration at C-2 in the ring. 

Because there are so many different compounds of carbon, there are many other variations on the theme of isomerism. Most of these are not as relevant to medicine as the ones described here. Some more complicated molecules have many centres of asymmetry in their structures, e.g. some proteins, carbohydrates etc. The body uses many specific molecules. Some cells only accept one type of isomer because the spatial arrangements inside the cell are very tight and only require certain shapes to fit a particular site. 

If enantiomers are derivatized with a chiral, optically pure reagent a pair of diastereomers is formed. Diastereomers are molecules with more than one centre of asymmetry, which therefore differ in their physical properties. From the scheme in Figure 22.5 it is clear that they are not mirror images. Diasetereomers can be separated with a nonchiral chromatographic system, but in any case the derivatization reagent must be chosen very carefully. 

It is favourable for the functional group to be derivatized to be situated close to the chiral centre of the molecule. Too large a distance from the centre of asymmetry can lead to the impossibility to resolve the diastereomers. If possible one should try to form amides, carbamates or ureas. All these classes of compounds have a relatively rigid structure (in comparison with, for example, esters) which seems to facilitate the separation. If a choice is possible, one of the reagent s isomers should be taken that allows the minor compound of the pair of enantiomers to be eluted first then the small peak will not be lost in the tailing of the leading large one. 

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