Enantiomer indirect

It becomes obvious from the clustered data points that the binding constant for the 7 -enantiomer is too small to be accurately determined by this method. Hence, indirect affinity CE (resolution method) was utilized to determine the binding constant for the 7 -enantiomer. Indirect affinity CE makes use of the knowledge of the constant for one enantiomer (here, A s) and in addition of experimental separation data as obtained with the racemate of DNB-Leu in presence of the tBuCQN selector as BGE additive. By use of Equation 1.10, an enantioselectivity factor may be defined as the ratio of the binding constants of S- and 7 -enantiomers yielding the following equation ... 

Monoisopinocampheylborane [64234-27-17, IpcBH2 (6) is an important asymmetric hydroborating agent. It is prepared from a-pinene (7) either directiy or better by indirect methods. The product obtained by hydroboration of a-pinene [80-56-8] is an equiUbrium mixture. Optically pure monoisopinocampheylborane is best prepared from a-pinene via diisopinocampheylborane [1091-56-1] IPC2BH (8) (64,65). Both enantiomers are readily available. 

One of the most useful applications of chiral derivatization chromatography is the quantification of free amino acid enantiomers. Using this indirect method, it is possible to quantify very small amounts of enantiomeric amino acids in parallel and in highly complex natural matrices. While direct determination of free amino acids is in itself not trivial, direct methods often fail completely when the enantiomeric ratio of amino acid from protein hydrolysis must be monitored in complex matrices. 

Two recent reports described addition of nitrogen-centered nucleophiles in usefully protected fonn. Jacobsen reported that N-Boc-protected sulfonamides undergo poorly selective (salen) Co-catalyzed addition to racemic epoxides. However, by performing a one-pot, indirect kinetic resolution with water first (HKR, vide infra, Table 7.1) and then sulfonamide, it was possible to obtain highly enantiomer-ically enriched addition products (Scheme 7.39) [71]. These products were transformed into enantioenriched terminal aziridines in straightforward manner. 

To date, direct asymmetric synthesis of optically active chiral-at-metal complexes, which by definition leads to a mixture of enantiomers in unequal amounts thanks to an external chiral auxiUary, has never been achieved. The most studied strategy is currently indirect asymmetric synthesis, which involves (i) the stereoselective formation of the chiral-at-metal complex thanks to a chiral inductor located either on the ligand or on the counterion and then (ii) removal of this internal chiral auxiliary (Fig. 4). Indeed, when the isomerization of the stereogenic metal center is possible in solution, in-... 

Since all the physical properties of two given enantiomers are the same in the absence of a chiral, or optically active, medium, their chromatographic resolution needs a different approach from the relatively simple separation of geometrical isomers, stereoisomers or positional isomers. Two methods are used. The older technique of indirect resolution, requires conversion of the enantiomers to diastereoisomers using a suitable chiral reagent, followed by separation of the diastereoisomers on a non-chiral GC or LC stationary phase. This technique has now been largely superseded by direct resolution, using either a chiral mobile phase (in LC) or a chiral stationary phase. A variety of types of chiral stationary phase have been developed for use in GC, LC and SFC(21 23). 

Peter, A. et al., A comparison of the direct and indirect LC methods for separating enantiomers of unusual glycine and alanine amino acid analogues, Chromatographia, 56, S79, 2002. 

Separation of enantiomers can be performed via two different kinds of approaches, direct and indirect ones. In the indirect approach the enantiomers are derivatized prior to their separation, while in the direct approach they are placed in a chiral environment and are not subjected to a chemical reaction. 

The indirect approach has been widely applied since many functional groups can be derivatized with various chiral reagents and the covalent diastereoisomers can be separated with inexpensive non-chiral systems. Other advantages of the indirect approach are that method development is rather straightforward and that the detection sensitivity of the enantiomers can be improved by the selection of an appropriate CDR having a strong chromophor or fluorophor. 

As discussed in previous sections, adding a chiral selector to CZE (see Section III.A.2) or MEKC (see Section III.C) buffers, either directly or indirectly using PET, is possible for analysis of CE—ESI/MS enantiomers. However, the use of such chiral selectors or additives can produce a significant enhancement of background noise. An alternative is to attach or bond the chiral selector as a chiral stationary phase (CSP) either to a packed-CEC or monolithic-CEC column, or to an OT-CEC column. ... 

As discussed earlier, the concepts of chiral chromatography can be divided into two groups, the indirect and the direct mode. The indirect technique is based on the formation of covalently bonded diastereomers using an optically pure chiral derivatizing agent (CDA) and reacting it with the pair of enantiomers of the chiral analyte. The method of direct enantioseparation relies on the formation of reversible quasi diastereomeric transient molecule associates between the chiral selector, e.g., i /t)-SO, and the enantiomers of the chiral selectands, [R,S)-SAs [(Ry SA + (S)-SA] (Scheme 1). 

In order to generally categorize the reaction schemes mentioned previously and the following ones in the course of indirect enantioseparation techniques, it has to be emphasized again, that the reciprocity principle should always be applicable. This means that if a chiral acid as the CDA can be used successfully to resolve the enantiomers of a chiral amine, then this optically pure amine as the CDA will equally well separate the enantiomers of the acid by the indirect method. The OPA reaction (see Figure 4) is therefore equally well suited for analyzing the optical purity of thiols, amines or amino acids. 

Wynberg studied stereochemistry of the McMurry reductive dimerization of camphor in detail (64). In Scheme 37, A and B are homochiral dimerization products derived by the low-valence Ti-promoted reduction, while C and D are achiral heterochiral dimers. The reaction of racemic camphor prefers homochiral dimerization (total 64.9%) over the diastereomeric heterochiral coupling (total 35.1 %). Similarly, as illustrated in Scheme 38, oxidative dimerization of the chiral phenol A can afford the chiral dimers B and C (and the enantiomers) or the meso dimer D. In fact, a significant difference is seen in diastereoselectivity between the enaritiomerically pure and racemic phenol as starting materials. The enantiomerically pure S substrate produces (S,S)-B exclusively, while the dimerization of the racemic substrate is not stereoselective. In the latter case, some indirect enantiomer effect assists the production of C, which is absent in the former reaction. Thus, it appears that, even though the reagents and reaction conditions are identical, the chirality of the substrate profoundly affects the stability of the transition state. 

I. Review on indirect separation of enantiomers as diastereomeric derivatives using UV, fluorescence and electrochemical detection, Biomed. Chromatogr., 6 163 (1992). 

The single enantiomer of indinavir has five stereogenic centers, four of which are derived either directly or indirectly from epoxide (27). Synthesis of indinavir sulfate developed by Merck is shown in Scheme-3. 

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