Enantiomer isolation

RS- P-Aminoisobutyric acid (a-methyl-P-alanine) [10569-72-9] M 103.1, m 176-178 , 178-180 , 181-182 , R -(-)- isomer [144-90-1] m 183 , [a] -21 (c 0.43, HjO), pKes,(,) 3.7, pKEst(2) 10.2. Colorless prisms from hot H O, were powdered and dried in vacuo. The purity is checked by paper chromatography (Whatman 1) using ninhydrin spray to visualise the amino acid Rp values in 95% MeOH and n-PrOH/5N HCOOH (8 2) are 0.36 and 0.50 respectively. [Kupiecki and Coon Biochem Prep 7 20 7960 Pollack J Am Chem Soc 65 1335 7943.] The R-enantiomer, isolated from iris bulbs or human urine was crystd from H2O and sublimed in vacuo [Asen et al. J Biol Chem 234 343 7959]. The RS-hydrochloride was recrystd from EtOH/Et20 m 128-129 , 130° [Bbhme et al. Chem Ber92 1258, 1260, 1261 7959]. 

If the test article is an enantiomer isolated from a mixture that is already well characterized (e.g., already on the market), then appropriate bridging guides need to be performed which compare the toxicity of the isomer to that of the racemic mixture. The most common approach would be to conduct a subchronic (three months) and a Sement II-type teratology study with an appropriate positive control group which received the racemate. In most instances no additional studies would be required if the enantiomer and the racemate did not differ in toxicity profile. If, on the other hand, differences are identified, that the reasons for this difference need to be investigated and the potential implications for human subjects need to be considered. 

In a review, Dufosse et al. (1994) mentioned the flavor thresholds of some lactones, particularly the olfactory perception after dispersion in water and the perception in mouth after dispersion in aqueous or deodorized oily solution. They also insist on the different sensory properties of y-lactone enantiomers isolated by Mosandl and Gunther (1989). Guichard et al. (1990) studied the lactones in apricot cultivars and found that the (7 )-enantiomer is always predominant for the y-Q, to y-C)2 lactones (Q, C9 and Go lactones have been identified in green coffee). Certainly because of the small amount present, no study has been conducted in coffee, to our knowledge, on the enantiomeric distribution of the lactones. 

Scheme 7. Examples for Enantiomer Separations by Crystallization with TADDOLs. Besides the original TADDOL (from tartrate acetonide and PhMgX), Toda et al. [44] have often used the cyclopentanone- and cyclohexanone-derived analogs. The dynamic resolution (resolution with in-situ recychng) of 2-(2-methoxyethyl)cyclohexanone was reported by Tsunoda et al. The resolved compounds shown here are only a small selection from a large number of successful resolutions, which include alcohols, ethers, oxiranes, ketones, esters, lactones, anhydrides, imides, amines, aziridines, cyanohydrins, and sulfoxides. The yields given refer to the amount of guest compound isolated in the procedure given. Since we are not dealing with reactions (for which we use % es to indicate enantioselectivity with which the major enantiomer is formed), we use % ep (enantiomeric purity of the enantiomer isolated from the inclusion...

Biochemical Preparations 7 20 1960, Pollack Jri/w Chem Soc 65 1335 1943.] The R-enantiomer, isolated from... 

Based on the optical rotation of the pure enantiomer. Isolated yield. 

As result of such a polymerization an optically active polymer with single stereoisomer units is produced and the unreacted monomer is enriched in antipode of opposite configuration. In ideal case the reaction should stop at 50 %yield and a pure enantiomer isolated. In most of the cases the reaction is not as perfect and only a preferential polymerization of one of the enantiomers from a mixture is observed. As seen, such a process could be a potentially interesting method for resolution of racemic monomers (38). 

An example of a chiral compound is lactic acid. Two different forms of lactic acid that are mirror images of each other can be defined (Figure 2-69). These two different molecules are called enantiomers. They can be separated, isolated, and characterized experimentally. They are different chemical entities, and some of their properties arc different (c.g., their optical rotation),... 

Cholesterol when isolated from natural sources is obtained as a single enantiomer The observed rotation a of a 0 3 g sample of cholesterol in 15 ml of chloroform solution contained in a 10 cm polarimeter tube is -0 78° Cal culate the specific rotation of cholesterol... 

Steroids are another class of natural products with multiple chirality centers One such compound is cholic acid which can be obtained from bile Its structural formula IS given m Figure 7 12 Cholic acid has 11 chirality centers and so a total (including cholic acid) of 2" or 2048 stereoisomers have this constitution Of these 2048 stereoiso mers how many are diastereomers of cholic acid s Remember Diastereomers are stereoisomers that are not enantiomers and any object can have only one mirror image Therefore of the 2048 stereoisomers one is cholic acid one is its enantiomer and the other 2046 are diastereomers of cholic acid Only a small fraction of these compounds are known and (+) cholic acid is the only one ever isolated from natural sources... 

Integration of the peaks for the two diastereomers accurately quantifies the relative amounts of each enantiomer within the mixture. Such diastereometic derivatives may also be analy2ed by more accurate methods such as gc or hplc. One drawback to diastereometic detivatization is that it requites at least 15 mg of material, which is likely to be material painstakingly synthesized, isolated, and purified. The use of analytical chiral chromatographic methods allows for the direct quantification of enantiomeric purity, is highly accurate to above 99.8% ee, and requites less than one milligram of material. 

Lactisole [13794-15-5] the sodium salt of racemic 2(4-methoxyphenoxy)propionic acid, is a sweet-taste inhibitor marketed by Domino Sugar. It was affirmed as a GRAS flavor (FEMA no. 3773). At a concentration of 100 to 150 ppm, lactisole strongly reduces or eliminates the sweet taste of a 10% sugar solution. This inhibition appears to be receptor-related because lactisole also inhibits the sweet taste of aspartame. The 5 -( —)-enantiomer [4276-74-8] (38), isolated from roasted coffee beans, is the active isomer the i -(+)-enantiomer is inert (127). 

The variety of enzyme-catalyzed kinetic resolutions of enantiomers reported ia recent years is enormous. Similar to asymmetric synthesis, enantioselective resolutions are carried out ia either hydrolytic or esterification—transesterification modes. Both modes have advantages and disadvantages. Hydrolytic resolutions that are carried out ia a predominantiy aqueous medium are usually faster and, as a consequence, require smaller quantities of enzymes. On the other hand, esterifications ia organic solvents are experimentally simpler procedures, aHowiag easy product isolation and reuse of the enzyme without immobilization. 

Synthetic chiral adsorbents are usually prepared by tethering a chiral molecule to a silica surface. The attachment to the silica is through alkylsiloxy bonds. A study which demonstrates the technique reports the resolution of a number of aromatic compoimds on a 1- to 8-g scale. The adsorbent is a silica that has been derivatized with a chiral reagent. Specifically, hydroxyl groups on the silica surface are covalently boimd to a derivative of f -phenylglycine. A medium-pressure chromatography apparatus is used. The racemic mixture is passed through the column, and, when resolution is successful, the separated enantiomers are isolated as completely resolved fiactions. Scheme 2.5 shows some other examples of chiral stationary phases. 

Certain substituted aziridines can be isolated as enantiomers as the result of still higher barriers. Most of these compounds are A -chloro- or iV-alkoxyaziridines. ... 

The minor images of bromochlorofluoromethane have the sane constitution. That is, the atoms are connected in the sane order. But they differ in the anangement of then-atoms in space they are stereoisomers. Stereoisomers that are related as an object and its nonsuperimposable minor image are classified as enantiomers. The word enantiomer describes a paiticulai- relationship between two objects. One cannot look at a single molecule in isolation and ask if it is an enantiomer any more than one can look at an individual human being and ask, Is that person a cousin Fuithennore, just as an object has one, and only one, minor image, a chiral molecule can have one, and only one, enantiomer. 

For the cycloaddition reaction in Scheme 4.6 it was found that 3-bromocam-phor, for example, can bind selectively to one enantiomer of the complex [12] and that if the reaction was performed in the presence of the racemic catalyst 8 and 3-bromocamphor, cis-3 was isolated with up to 80% ee compared to 95% ee for the reaction catalyzed by (J )-8b. 

The recognition of differences in the pharmacological activity of enantiomeric molecules has created the need to administer them - and therefore to obtain them -as isolated enantiomers. However, nowadays this problem affects not only the pharmaceutical industry, but also the agrochemical industry and food additive producers, both of which are increasingly concerned by this subject. 

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