Asymmetric compounds

Pfeiffer effect The change in rotation of a solution of an optically active substance on the addition of a racemic mixture of an asymmetric compound. 

Care should be exercised when attempting to interpret in vivo pharmacological data in terms of specific chemical—biological interactions for a series of asymmetric compounds, particularly when this interaction is the only parameter considered in the analysis (10). It is important to recognize that the observed difference in activity between optical antipodes is not simply a result of the association of the compound with an enzyme or receptor target. Enantiomers differ in absorption rates across membranes, especially where active transport mechanisms are involved (11). They bind with different affinities to plasma proteins (12) and undergo alternative metaboHc and detoxification processes (13). This ultimately leads to one enantiomer being more available to produce a therapeutic effect. 

Normal Fluids. Asymmetrical compounds having Httle molecular interaction, eg, carbon monoxide, / -butane, and / -hexane, deviate slightly from the theory of corresponding states and are considered to be normal fluids. 

Because of the somewhat ambiguous definitions of D and L, another system of nomendature was devised for asymmetric compounds, and it has largely replaced the old D, L-system since the 1960s. However, the D, L-nomendature is still used for amino adds and sugars. 

The rearrangement has also been extended to P-chiral S-phenyl phos-phinothiolate 79 and 0-phenyl phosphinothioate 80 (Scheme 21). With these asymmetric compounds, the C-P bond formation was found to occur stereose-lectively and with retention of configuration at phosphorus [51]. 

Compounds containing a carbon atom united with four different atoms or groups are called asymmetric compounds and this carbon atom is called an asymmetric carbon atom. Originally the presence of an asymmetric carbon atom was regarded to impart optical activity. But later compounds were discovered which showed optical activity but were devoid of asymmetric carbon atoms, e.g., methyl cyclo-hexylidence acetic acid. 

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. 

On the other hand, according to E. Fischer, the asymmetric compounds produced with the mediation of living organisms are almost invariably active. We now proceed to find the reasons for this. 

The synthesis of an asymmetric compound carried under the influence of an optically active molecule or group is termed asymmetric synthesis. 

The asymmetric synthesis explains why most asymmetric compounds obtained from natural sources are optically active. In nature, the syntheses are carried out under the influence of optically active enzymes. The enzymes unite with the substance and when the synthesis is complete, they separate from the product and are again free to combine with fresh molecules of the original substance. 

In principle, dimeric molecules may also be made out of different halves leading to asymmetric compounds. Different substituted arylamines have been coupled by Thompson et al. [66]. Tme bipolar compounds with a different electronic character in each half will be discussed in Section VI in the context of their redox properties. Despite their polar character, the tendency toward crystallization can be low, and amorphous films are obtained. 

By the same method, the asymmetrical compounds 196a and 196b (from alkenes 195a and 195b), the related dilithiated compounds of tetrakis(dimethylsilyl)ethylene (197) and the tetrasilabicyclopentylidene 198 were accessible (Scheme 66) . The results of the X-ray structural analyses are shown (Figures 23 and 24). 

Ester groups at the C3 and C5 positions optimize activity when the C3 and C5 esters are nonidentical, the C4 carbon becomes chiral such asymmetrical compounds exhibit enhanced selectivity for specific blood vessels... 

Ammino-derivatives of Platinum Salts—Derivatives of Platinous Salts— Derivatives of Platinio Saits—Derivatives containing Hydroxylamine and Hydrazine in place of Ammonia—Symmetrical and Asymmetrical Compounds—Diplato-animino-salts—Diplati-ammino-salts. 

According to J. Meisenheimer and L. Lichtenstadt, when phosphine oxide, 0 PH3, has its hydrogen atoms replaced by three different radicles, the asymmetric compounds are optically active—e.g. 0 P(C6H5)(C2H5)(CH3). P. Pascal also said that the magnetic properties are in agreement with the formula 0 PH3. 

Cyano-substituted 1,4-distyrylbenzenes (Table 7.1) are carbocyclic brighteners with a very high whiteness and good efficiency for plastics and synthetic fibers, especially polyesters [28], Asymmetrical compounds, mixtures of two or three dif-... 

The first important member of this group was 4,4 -bis(6-sulfonaphtho 1,2-disulfonic acid. As the tetrasodium salt [7426-67-7] [57], however, it produced a greenish white brightening effect on cotton. Removal of one of the naphthotriazole groups resulted in asymmetric compounds giving a neutral white, but at the cost of efficiency, e.g., the sodium salt of 4-(2H-naphtho[l,2-rf ]triazol-2-yl)stilbene-2-sulfonic acid [58],... 

Another scenario for the origin of homochirality was suggested by Pearson [8,9] such that chance breaks the chiral symmetry. Though the mean number of right- and left-handed enantiomers are the same, there is a nonzero probability of deviation from the equal populations of both enantiomers. The probability of establishing homochirality in a macroscopic system is, of course, very small [10], but chance produces a slight majority of one type of enantiomer and asymmetric compounds when they have once arisen act as breeders, with a power of selecting their own kind of asymmetry form [8,9]. In this scenario, produced enantiomer acts as a chiral catalyst for the production of its own kind and hence this process should be autocatalytic. 

A particular class of modified electrodes consists of those containing a layer of asymmetric compounds, and such electrodes are termed chiral. If one uses these electrodes in organic synthesis, the compound produced may also be asymmetric and optically active. One of the better-known examples of such phenomena is called the Sharpless process (Finn and Sharpless, 1986 Katsuki, 1996). In such processes, the electrode is modified by asymmetric compounds that lead to epoxidation and dihy-droxylation of olefenic compounds, but in an asymmetric form. An example is shown in Fig. 11.5, in which the hydroxylation occurs either on the top or the bottom of the enantiomorphic surface. 

It is important to note that uroporphyrinogen III is an asymmetric compound with respect to its side chains. In the absence of uroporphyrinogen III cosynthase, hydroxymethyl bilane is converted nonenzymatically to the symmet-... 

The need for optically pure asymmetric compounds for biochemical and pharmacological evaluation arises for the following reasons. Where the difference in the potency of enantiomers is large (and many examples are known in which one enantiomer is more than a hundred times as potent as the other), the presence of 1% or less of the active isomer as a contaminant of the less active (or inactive) isomer can account for all or almost all of the activity of the less active (or inactive) isomer,32 thereby vitiating the value of any results obtained from the more sophisticated type of pharmacological experiment.33 The difficulties associated with methods for obtaining enantiomers having unequivocal optical purity constitute a major impediment to such studies. As the classical methods of resolution do not necessarily... 

In the meso-trick the same principle is applied [25]. A symmetric compound, in this case a meso compound, is submitted to selective hydrolysis. The asymmetric compound that is generated in this manner is obtained in 100% yield and ideally high optical purity (Scheme 6.8). Meso compounds with diamino, diol or diacid functions can be converted to chiral mono-esters or mono-amides, too, if the reaction is performed in organic solvents [22, 24, 27]. 

The stereogenic center at C20 is introduced by enantioselective enzymatic hydrolysis of MOM-protected malonic acid dimethyl ester derivative 60 (Scheme 10) with pig liver esterase (PLE). The asymmetric compound 61 is obtained in 90 % yield and 98 % ee. Amide formation with Mu-... 

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