Enantiomer converter

Racemization is the process by which one enantiomer converts to the other. In normal circumstances, organic compounds which may exhibit optical activity (such as simple sugars) exist in solution as equal numbers of d- and l- forms. 

Crans, D.C., F. Jiang, I. Boukhobza, I. Bodi, and T. Kiss. 1999. Solution characterization of vanadium(V) and -(IV) V-(phosphonomethyl)iminodiacetate complexes Direct observation of one enantiomer converting to the other in an equilibrium mixture. Inorg. Chem. 38 3275-3282. 

Granvil et al. [238] found that in their female patients, the AUC ratio of dechloroethyl metabolites of ifosfamide to AUC of parent drug was higher for the S enantiomer than R-ifosfamide. Consistent with the in vitro results outlined above, this may suggest a higher extent of S enantiomer converted to these metabolites and/or a lower CL of these dechloroethylated metabolites formed from S-ifosfamide, compared with that of metabolites formed from the R enantiomer. 

S-enantiomer converted to R-enantiomer using Mitsunobu reaction and 3,5-dinitro-benzoic acid in 91% yieid. Totai yieid of R-enantiomer is 61% with 95% recovery of cyciodexthn. 

Optically active catalysts can kinetically resolve racemic monomers (Scheme 2) via enantioselective polymerization producing optically active polymers as well as enantiomerically enriched monomers. The nonpreferred enantiomer remains unreacted in the reaction mixture after the prefened enantiomer of monomer has been enchained as a polymer. The quantitative measure of stereocontrol in such a system is given by the selectivity factor (s-factor, s), which is the ratio of the rate constants for the polymerization of the fast enantiomer converted to polymer with respect to the slow enantiomer enchained [s = fefast/fesiow = /(l- )] ( is the probability that the preferred enantiomer will be selected by the catalyst). A racemic enantioselective catalyst can polymerize both enantiomers of racemic monomer via isoselective polymerization to give racemic isotactic polymer. 

HC CH(0H) CH20H. optically active. D-glyceraldehyde is a colourless syrup. May be prepared by mild oxidation of glycerol or by hydrolysis of glyceraldehyde acetal (prepared by oxidation of acrolein acetol). DL-glyceraldehyde forms colourless dimers, m.p. IBS-S C. Converted to methylglyoxal by warm dilute sulphuric acid. The enantiomers... 

A phase change takes place when one enantiomer is converted to its optical isomer. As illustrated in Figure 9, when the chiral center is a tetra-substituted carbon atom, the conversion of one enantiomer to the other is equivalent to the exchange of two electron pairs. This transformation is therefore phase inverting. 

A similar situation holds foi a molecule containing a tetrahedral carbon is shown in (Figure 16). The reaction converting one enantiomer to another, is formally equivalent to the exchange of two sigma-bond electr on pair s, and... 

In this example addition to the double bond of an alkene converted an achiral mol ecule to a chiral one The general term for a structural feature the alteration of which introduces a chirality center m a molecule is prochiral A chirality center is introduced when the double bond of propene reacts with a peroxy acid The double bond is a prochi ral structural unit and we speak of the top and bottom faces of the double bond as prochiral faces Because attack at one prochiral face gives the enantiomer of the com pound formed by attack at the other face we classify the relationship between the two faces as enantiotopic... 

When a reactant is chiral but optically inactive because it is racemic any products derived from its reactions with optically inactive reagents will be optically inactive For example 2 butanol is chiral and may be converted with hydrogen bromide to 2 bromo butane which is also chiral If racemic 2 butanol is used each enantiomer will react at the same rate with the achiral reagent Whatever happens to (/ ) (—) 2 butanol is mir rored m a corresponding reaction of (5) (+) 2 butanol and a racemic optically inactive product results... 

To convert a molecule with two chirality centers to its enantiomer the configura tion at both centers must be changed Reversing the configuration at only one chirality center converts it to a diastereomeric structure... 

Among all the isomers as 1 2 dichlorocycio hexane is unique in that the ring flipping process typ ical of cyclohexane derivatives (Section 3 9) converts it to its enantiomer... 

Structures A and A are nonsuperimposable mirror images of each other Thus although as 1 2 dichloro cyclohexane is chiral it is optically inactive when chair-chair interconversion occurs Such interconver Sion IS rapid at room temperature and converts opti cally active A to a racemic mixture of A and A Because A and A are enantiomers interconvertible by a conformational change they are sometimes re ferred to as conformational enantiomers... 

The same kind of spontaneous racemization oc curs for any as 1 2 disubstituted cyclohexane in which both substituents are the same Because such compounds are chiral it is incorrect to speak of them as meso compounds which are achiral by definition Rapid chair-chair interconversion however converts them to a 1 1 mixture of enantiomers and this mix ture IS optically inactive... 

Section 7 14 Resolution is the separation of a racemic mixture into its enantiomers It IS normally carried out by converting the mixture of enantiomers to a mixture of diastereomers separating the diastereomers then regenerating the enantiomers... 

Enzyme catalyzed reductions of carbonyl groups are more often than not com pletely stereoselective Pyruvic acid for example is converted exclusively to (5) (+) lactic acid by the lactate dehydrogenase NADH system (Section 15 11) The enantiomer... 

The reaction is used for the chain extension of aldoses in the synthesis of new or unusual sugars In this case the starting material l arabinose is an abundant natural product and possesses the correct configurations at its three chirality centers for elaboration to the relatively rare l enantiomers of glucose and mannose After cyanohydrin formation the cyano groups are converted to aldehyde functions by hydrogenation m aqueous solution Under these conditions —C=N is reduced to —CH=NH and hydrolyzes rapidly to —CH=0 Use of a poisoned palladium on barium sulfate catalyst prevents further reduction to the alditols... 

Enantiomers (Section 7 1) Stereoisomers that are related as an object and its nonsupenmposable mirror image Enantioselective synthesis (Section 27 4) Reaction that converts an achiral or racemic starting material to a chiral product in which one enantiomer is present in excess of the other... 

Enzymatic hydrolysis is also used for the preparation of L-amino acids. Racemic D- and L-amino acids and their acyl-derivatives obtained chemically can be resolved enzymatically to yield their natural L-forms. Aminoacylases such as that from Pispergillus OTj e specifically hydrolyze L-enantiomers of acyl-DL-amino acids. The resulting L-amino acid can be separated readily from the unchanged acyl-D form which is racemized and subjected to further hydrolysis. Several L-amino acids, eg, methionine [63-68-3], phenylalanine [63-91-2], tryptophan [73-22-3], and valine [72-18-4] have been manufactured by this process in Japan and production costs have been reduced by 40% through the appHcation of immobilized cell technology (75). Cyclohexane chloride, which is a by-product in nylon manufacture, is chemically converted to DL-amino-S-caprolactam [105-60-2] (23) which is resolved and/or racemized to (24)... 

Because the starting materials were optically active, the products were all pure enantiomers. Later, the synthetic scheme shown in Figure 5 was developed (22,45). Resolution of the racemic mixture was accompHshed at the penultimate stage and the optically active D-threo-amine (7) was converted to florfenicol (2). This synthetic process also resulted in the synthesis of thiamphenicol shown in Figure 6 using 1,1,2,3,3,3-hexafluoropropyl diethylamine (FPA) (46). More recently an improved method of synthesis of florfenicol has been developed (17). 

The situation is different if the substrate is a prochiral or meso compound. Since these molecules have a center or plane of symmetry the binding of pro-S or pro-R forms is equivalent. The chirahty appears only as a result of the transformation. Hence, at least theoretically, the compound can be converted to one enantiomer quantitatively. 

Optically Active Acids and Esters. Enantioselective hydrolysis of esters of simple alcohols is a common method for the production of pure enantiomers of esters or the corresponding acids. Several representative examples are summarized ia Table 4. Lipases, esterases, and proteases accept a wide variety of esters and convert them to the corresponding acids, often ia a highly enantioselective manner. For example, the hydrolysis of (R)-methyl hydratropate [34083-55-1] (40) catalyzed by Hpase P from Amano results ia the corresponding acid ia 50% yield and 95% ee (56). Various substituents on the a-carbon (41—44) are readily tolerated by both Upases and proteases without reduction ia selectivity (57—60). The enantioselectivity of many Upases is not significantly affected by changes ia the alcohol component. As a result, activated esters may be used as a means of enhancing the reaction rate. 

The property of chirality is determined by overall molecular topology, and there are many molecules that are chiral even though they do not possess an asymmetrically substituted atom. The examples in Scheme 2.2 include allenes (entries 1 and 2) and spiranes (entries 7 and 8). Entries 3 and 4 are examples of separable chiral atropisomers in which the barrier to rotation results from steric restriction of rotation of the bond between the aiyl rings. The chirality of -cyclooctene and Z, -cyclooctadiene is also dependent on restricted rotation. Manipulation of a molecular model will illustrate that each of these molecules can be converted into its enantiomer by a rotational process by which the ring is turned inside-out. ... 

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