Isomer selective search

The theory of the separation of geometric isomers on stationary phases that have a number of sterogenic centers has not been developed to the point where a particular stationary phase together with an appropriate mobile phase can be deduced for the separation of a specific pair of isomers. A number of theories have been put forward to explain the resolution of geometric isomers (some of which have been quite "imaginative" and "colorful") yet a reliable theory to help in phase selection for a hitherto unresolved chiral pair is still lacking. Unfortunately, the analyst is left with only two alternatives. The first is to search the literature for a model separation similar to the problem in hand and start with that phase system or, alternatively, resort to the technique of the early days of LC, namely, find the best phase system by a trial-and-error routine. 

The search for catalysts which are able to reverse the ratio of cyclopropane diastereomers in favor of the thermodynamically less stable isomer has met with only moderate success to date. Rh(II) pivalate and some ring-substituted Rh(II) benzoates induce cw-selectivity in the production of permethric acid esters 77,98 99 contrary to rhodium(II) acetate, which gives a 1 1 mixture 74,77,98), and some copper catalysts 98) (Scheme 10). 

The selective serotonin reuptake inhibitors (SSRIs) represent a chemically diverse class of agents that have as their primary action the inhibition of the serotonin transporter (SERT) (Figure 30-3). Fluoxetine was introduced in the United States in 1988 and quickly became one of the most commonly prescribed medications in medical practice. The development of fluoxetine emerged out of the search for chemicals that had high affinity for monoamine receptors but lacked the affinity for histamine, acetylcholine, and adrenoceptors that is seen with the tricyclic antidepressants (TCAs). There are currently six available SSRIs, and they are the most common antidepressants in clinical use. In addition to their use in major depression, SSRIs have indications in GAD, PTSD, OCD, panic disorder, PMDD, and bulimia. Fluoxetine, sertraline, and citalopram exist as isomers and are formulated in the racemic forms, whereas paroxetine and fluvoxamine are not optically active. Escitalopram is the S enantiomer of citalopram. As with all antidepressants,... 

Numerous substituents were explored at the para position of this phenyl ring, in search of potent, selective delta opioid receptor agonists. It is important to note at this point that in the 1980s, when much of this work took place, it was often more efficient to test mixtures of stereoisomers to quickly look for potent delta opioid receptor agonists than to separate out the individual isomers (stereoselective routes were eventually developed to reduce the need for difficult separations). For this reason, selectivity data (especially... 

In search for control of absolute stereochemistry, the reaction of thio-chalcones was investigated with unsaturated amides bearing an Evans chiral oxazolidinone [223] and dimenthyl fumarate [224, 225]. For the first time with thiocarbonyl compounds, the efficiency of Lewis acid addition was demonstrated, and reactions could be conducted at room temperature. With EtAlCl2 (Table 4, entry 2) or A1C13 (entry 3), levels of induction up to 92% were attained for the endo isomer. Yb(OTf)3 in DMSO also caused the acceleration of the reaction with chiral acrylamides with p-facial selectivity [226]. This group has also reported [227] an intramolecular hetero Diels-Alder reaction with divinyl thioketones and the double bond of an allyloxy group (Table 4, entry 4). 

Resolution problems in the GC analysis of FA esters prompted many investigators in the past to develop capillary techniques to search for more selective stationary phases, and ultimately, to combine both approaches whenever required. In fact, FA esters were among the first substances (beyond hydrocarbons) that were successfully chromatographed on stainless steel capillary columns [355]. The most difficult separations involve different geometrical isomers, and the presence and positions of unsaturated carbon-carbon bonds. Such separations are non-trivial and justify the effort of numerous laboratories to solve these problems. 

The dynamic method for selection of active conformers appears to be useful in this venture. Its first step is a procedure for generation of 3D isomers, representing the conformational space of molecules. Although the 3DGEN algorithm is used in the OASIS system, most of the other algorithms for conformational space search (after minor modifications) could be used for that purpose. Next, a method for conformer screening is nsed, based on a hierarchical set ofmles, in an attempt to find the active conformers. 

It is instructive to show that although contiguous addition appears to be the rule supported by both experimental and DFT studies, the other possibilities should not be completely abandoned. In the experimental studies of low Ceo fluorides, Cs-symmetric isomer of CeoFs was isolated (Boltalina et al. 2002). Cs symmetry is not compatible with the S-type string, and the authors proposed a contiguous addition pattern with T-motif and two additional fluorine atoms attached at the both ends of the string. However, later calculations have shown that such a structure would by unstable. Sandall and Fowler performed a broad search of aU possible structures of Cs symmetry compatible with NMR data (Sandall and Fowler 2003). After calculations of more than 500 isomers using MNDO, AMI, and PM3 methods and - for selected structures - Harree-Fock method with STO-3G and 6-31G basis sets, the authors have found that the most suitable... 

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