Racemic mixture, isomerism

Butyl alcohols encompass the four stmcturaHy isomeric 4-carbon alcohols of empirical formula C H qO. One of these, 2-butanol, can exist in either the optically active R — ) or configuration or as a racemic ( ) mixture [15892-23-6]. 

Discrimination between the enantiomers of a racemic mixture is a complex task in analytical sciences. Because enantiomers differ only in their structural orientation, and not in their physico-chemical properties, separation can only be achieved within an environment which is unichiral. Unichiral means that a counterpart of the race-mate to be separated consists of a pure enantiomeric form, or shows at least enrichment in one isomeric form. Discrimination or separation can be performed by a wide variety of adsorption techniques, e.g. chromatography in different modes and electrophoresis. As explained above, the enantioseparation of a racemate requires a non-racemic counterpart, and this can be presented in three different ways ... 

The steroid ring structure is complex and contains many chiral carbons (for example at positions 5, 8, 9,10,13,14 and 17) thus many optical isomers are possible. (The actual number of optical isomers is given by 2" where n = the number of chiral carbons). From your knowledge of biochemistry you should have realised that only one of these optical isomers is likely to be biologically active. Synthesis of such a complex chemical structure to produce a single isomeric form is extremely difficult, especially when it is realised that many chemical reactions lead to the formation of racemic mixtures. Thus, for complete chemical synthesis, we must anticipate that... 

When the natural product source contains racemic mixtures (of isomeric forms), then clearly the assignment of signal value to either or both variants of a compound needs to be determined. Alterations in receptor detection of chirality can change sensitivity to the geometrically alternate compound over the range 101 to 106. Of the lactones passed into urine and deposited on tarsal hairs of Black-tailed deer (Odocoileus... 

The answer is F. (Katzung, p 167, Hardman, pp 237-2382 Labetalol has potent a and p antagonist actions, due to the specific components of its racemic mixture of four isomeric compounds. Cardiac output and heart rate change minimally, while blood pressure decreases due to a overall reduction in peripheral resistance. The combined a and p antagonism has been found to be of advantage in treating pheochromocytomas. 

All amino acids except glycine exist in these two different isomeric forms but only the L isomers of the a-amino acids are found in proteins, although many D amino acids do occur naturally, for example in certain bacterial cell walls and polypeptide antibiotics. It is difficult to differentiate between the D and the L isomers by chemical methods and when it is necessary to resolve a racemic mixture, an isomer-specific enzyme provides a convenient way to degrade the unwanted isomer, leaving the other isomer intact. Similarly in a particular sample, one isomer may be determined in the presence of the other using an enzyme with a specificity for the isomer under investigation. The other isomer present will not act as a substrate for the enzyme and no enzymic activity will be demonstrated. The enzyme L-amino acid oxidase (EC 1.4.3.2), for example, is an enzyme that shows activity only with L amino acids and will not react with the D amino acids. 

Fenfluramine and its active isomere dexfenflu-ramine act by stimulating the release of serotonin and inhibiting its re-uptake. Dexfenluramine lacks the amphetamine-like properties of the racemic mixture which are due to L-fenfluramine. Both isomers have antiobesity activity but they were taken from the market, at least in several Western countries, because of rare but very serious cardiotoxicity. 

The efficient resolution of /ra r-4,5-dihydroxy-l,2-dithiane into the two enantiomers in large quantities has been reported by the reaction of the racemic mixture with the amino acid iV-/-butoxycarbonyl-(5)-phenylalanine <1997TL7657>. By fractional crystallization, the (43, 53 )- and (4/J,5iJ)-esters were separated followed by hydrolysis, which provided the desired enantiomeric diols in excellent yield and >99% ee. These reactive diols provide isomerically pure analogs with interesting selectivity and therapeutic potential for example, 4,5-dihydroxy-l,2-dithiane derivatives have been reported to inhibit the replication of HIV-1 and HIV-2 (human immunodeficiency viruses). 

Amphetamine and methamphetamine occur as structural isomers and stereoisomers. Structural isomers are compounds with the same empirical formula but a different atomic arrangement, e.g., methamphetamine and phentermine. Stereoisomers differ in the three-dimensional arrangement of the atoms attached to at least one asymmetric carbon and are nonsuperimposable mirror images. Therefore, amphetamine and methamphetamine occur as both d- and L-isomeric forms. The two isomers together form a racemic mixture. The D-amphetamine form has significant stimulant activity, and possesses approximately three to four times the central activity of the L-form. It is also important to note that the d- and L-enantiomers may have not only different pharmacological activity but also varying pharmacokinetic characteristics. 

Before 1940 optically active compounds could only be obtained in stereo-isomerically pure form by isolation from natural sources, by resolution of racemic mixtures, or by a few laboratory controlled enzymic reactions. Many of the chemical reactions described in this book lead to products which contain chiral centres, axes, or planes, but in which the isolated material is the optically inactive (racemic) form. This is a direct consequence of the fact that the reactants, reagents, or solvents are achiral or are themselves racemic. The following selection of reactions drawn from the text illustrate this statement they may be cross-referenced to the relevant discussion sections, namely (a) Section 5.4.1, p. 519, (b) Section 5.4.3, p.542, (c) Section 5.11.7, p.687, (d) Section 8.1.3, p. 1133, e) Section 5.2.4, p. 504 and (/) Section 5.4.2, p. 531. 

Additives that specifically interact with an analyte component are also very useful in altering the electrophoretic mobility of that component. For example, the addition of copper(II)-L-histidine (12) or copper(II)-aspartame (54) complexes to the buffer system allows racemic mixtures of derivatized amino acids to resolve into its component enantiomers. Similarly, cyclodextrins have proven to be useful additives for improving selectivity. Cyclodextrins are non-ionic cyclic polysaccharides of glucose with a shape like a hollow truncated torus. The cavity is relatively hydrophobic while the external faces are hydrophilic, with one edge of the torus containing chiral secondary hydroxyl groups (55). These substances form inclusion complexes with guest compounds that fit well into their cavity. The use of cyclodextrins has been successfully applied to the separation of isomeric compounds (56), and to the optical resolution of racemic amino acid derivatives (57). 

The reaction produces a racemic mixture of the product shown, (lR S)-2-bromo-1-phenyl-1-propanol and its enantiomer, the (I S,2R)-stereoisomer, in 92% yield. It is regiospecific, because none of the isomeric I-bromo-1-phenyl-2-propanol is formed. It is stereospecific, because none of the (I S,2S)-diastereomei or its enantiomer, the (I R,2R)-stereoisomer, is produced. 

The aminohydroxylation of racemic Baylis-Hillman alkenes provided regio-isomerically pure, racemic mixtures of the a - hydroxy- (3 - am i no esters, with the syn (diol) product as the major diastereomer (Table 11) [97]. The diastereoselectivity increased with increasing size of either the allylic substituent or the ester group. As observed in other studies of related substrates [53,103-105], neither the rate, the selectivity, nor the yield were noticeably affected when a chiral ligand (e.g., (DHQ)2PHAL) was added and enantioselective aminohydroxylation could not be obtained. 

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