Chirality temperature

Balss et al. [26] reported enantiomeric resolution of glutamic acid, dansyl-DL-glutamic acid, and baclofen with chiral temperature gradient focusing in... 

Balss, K.M., et al., Simultaneous concentration and separation of enantiomers with chiral temperature gradient focusing. Anal. Chem., 2004, 76 7243-7249. 

Chiral 2-oxazolidones are useful recyclable auxiliaries for carboxylic acids in highly enantioselective aldol type reactions via the boron enolates derived from N-propionyl-2-oxazolidones (D.A. Evans, 1981). Two reagents exhibiting opposite enantioselectivity ate prepared from (S)-valinol and from (lS,2R)-norephedrine by cyclization with COClj or diethyl carbonate and subsequent lithiation and acylation with propionyl chloride at — 78°C. En-olization with dibutylboryl triflate forms the (Z)-enolates (>99% Z) which react with aldehydes at low temperature. The pure (2S,3R) and (2R,3S) acids or methyl esters are isolated in a 70% yield after mild solvolysis. 

The 1,6-difunctional hydroxyketone given below contains an octyl chain at the keto group and two chiral centers at C-2 and C-3 (G. Magnusson, 1977). In the first step of the antithesis of this molecule it is best to disconnect the octyl chain and to transform the chiral residue into a cyclic synthon simultaneously. Since we know that ketones can be produced from add derivatives by alkylation (see p. 45ff,), an obvious precursor would be a seven-membered lactone ring, which is opened in synthesis by octyl anion at low temperature. The lactone in turn can be transformed into cis-2,3-dimethyicyclohexanone, which is available by FGI from (2,3-cis)-2,3-dimethylcyclohexanol. The latter can be separated from the commercial ds-trans mixture, e.g. by distillation or chromatography. 

The alkyl azide 118 is reduced to a primary amine by the Pd on carbon-catalyzed reaction of ammonium formate in MeOH at room temperature. No racemization takes place with chiral azides[l 11,112]. 

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... 

Trigonal pyramidal molecules are chiral if the central atom bears three different groups If one is to resolve substances of this type however the pyramidal inversion that mterconverts enantiomers must be slow at room temperature Pyramidal inversion at nitrogen is so fast that attempts to resolve chiral amines fail because of their rapid racemization... 

Section 7 16 Atoms other than carbon can be chirality centers Examples include those based on tetracoordmate silicon and Incoordinate sulfur as the chirality center In principle Incoordinate nitrogen can be a chirality center m compounds of the type N(x y z) where x y and z are different but inversion of the nitrogen pyramid is so fast that racemization occurs vrr tually instantly at room temperature... 

A similar effect occurs in highly chiral nematic Hquid crystals. In a narrow temperature range (seldom wider than 1°C) between the chiral nematic phase and the isotropic Hquid phase, up to three phases are stable in which a cubic lattice of defects (where the director is not defined) exist in a compHcated, orientationaHy ordered twisted stmcture (11). Again, the introduction of these defects allows the bulk of the Hquid crystal to adopt a chiral stmcture which is energetically more favorable than both the chiral nematic and isotropic phases. The distance between defects is hundreds of nanometers, so these phases reflect light just as crystals reflect x-rays. They are called the blue phases because the first phases of this type observed reflected light in the blue part of the spectmm. The arrangement of defects possesses body-centered cubic symmetry for one blue phase, simple cubic symmetry for another blue phase, and seems to be amorphous for a third blue phase. 

The positional order of the molecules within the smectic layers disappears when the smectic B phase is heated to the smectic A phase. Likewise, the one-dimensional positional order of the smectic M phase is lost in the transition to the nematic phase. AH of the transitions given in this example are reversible upon heating and cooling they are therefore enantiotropic. When a given Hquid crystal phase can only be obtained by changing the temperature in one direction (ie, the mesophase occurs below the soHd to isotropic Hquid transition due to supercooling), then it is monotropic. An example of this is the smectic A phase of cholesteryl nonanoate [1182-66-7] (4), which occurs only if the chiral nematic phase is cooled (21). The transitions are aH reversible as long as crystals of the soHd phase do not form. 

The polyamides are soluble in high strength sulfuric acid or in mixtures of hexamethylphosphoramide, /V, /V- dim ethyl acetam i de and LiCl. In the latter, compHcated relationships exist between solvent composition and the temperature at which the Hquid crystal phase forms. The polyamide solutions show an abmpt decrease in viscosity which is characteristic of mesophase formation when a critical volume fraction of polymer ( ) is exceeded. The viscosity may decrease, however, in the Hquid crystal phase if the molecular ordering allows the rod-shaped entities to gHde past one another more easily despite the higher concentration. The Hquid crystal phase is optically anisotropic and the texture is nematic. The nematic texture can be transformed to a chiral nematic texture by adding chiral species as a dopant or incorporating a chiral unit in the main chain as a copolymer (30). 

An hplc assay was developed suitable for the analysis of enantiomers of ketoprofen (KT), a 2-arylpropionic acid nonsteroidal antiinflammatory dmg (NSAID), in plasma and urine (59). Following the addition of racemic fenprofen as internal standard (IS), plasma containing the KT enantiomers and IS was extracted by Hquid-Hquid extraction at an acidic pH. After evaporation of the organic layer, the dmg and IS were reconstituted in the mobile phase and injected onto the hplc column. The enantiomers were separated at ambient temperature on a commercially available 250 x 4.6 mm amylose carbamate-packed chiral column (chiral AD) with hexane—isopropyl alcohol—trifluoroacetic acid (80 19.9 0.1) as the mobile phase pumped at 1.0 mL/min. The enantiomers of KT were quantified by uv detection with the wavelength set at 254 nm. The assay allows direct quantitation of KT enantiomers in clinical studies in human plasma and urine after adrninistration of therapeutic doses. 

The separation of Hquid crystals as the concentration of ceUulose increases above a critical value (30%) is mosdy because of the higher combinatorial entropy of mixing of the conformationaHy extended ceUulosic chains in the ordered phase. The critical concentration depends on solvent and temperature, and has been estimated from the polymer chain conformation using lattice and virial theories of nematic ordering (102—107). The side-chain substituents govern solubiHty, and if sufficiently bulky and flexible can yield a thermotropic mesophase in an accessible temperature range. AcetoxypropylceUulose [96420-45-8], prepared by acetylating HPC, was the first reported thermotropic ceUulosic (108), and numerous other heavily substituted esters and ethers of hydroxyalkyl ceUuloses also form equUibrium chiral nematic phases, even at ambient temperatures. 

Alcohol dehydrogenase-catalyzed reduction of ketones is a convenient method for the production of chiral alcohols. HLAD, the most thoroughly studied enzyme, has a broad substrate specificity and accommodates a variety of substrates (Table 11). It efficiendy reduces all simple four- to nine-membered cycHc ketones and also symmetrical and racemic cis- and trans-decalindiones (167). Asymmetric reduction of aUphatic acycHc ketones (C-4—C-10) (103,104) can be efficiendy achieved by alcohol dehydrogenase isolated from Thermoanaerohium hrockii (TBADH) (168). The enzyme is remarkably stable at temperatures up to 85°C and exhibits high tolerance toward organic solvents. Alcohol dehydrogenases from horse Hver and T. hrockii... 

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