Chiral forms, determination

Capillary zone electrophoresis 201-212 Chiral forms, determination of 69-71, 126, 218-222... 

Considerable ingenuity was required in both the synthesis of these chiral compounds695 697 and the stereochemical analysis of the products formed from them by enzymes.698 700 In one experiment the phospho group was transferred from chiral phenyl phosphate to a diol acceptor using E. coli alkaline phosphatase as a catalyst (Eq. 12-36). In this reaction transfer of the phospho group occurred without inversion. The chirality of the product was determined as follows. It was cyclized by a nonenzymatic in-line displacement to give equimolar ratios of three isomeric cyclic diesters. These were methylated with diazomethane to a mixture of three pairs of diastereoisomers triesters. These dia-stereoisomers were separated and the chirality was determined by a sophisticated mass spectrometric analysis.692 A simpler analysis employs 31P NMR spectroscopy and is illustrated in Fig. 12-22. Since alkaline phosphatase is relatively nonspecific, most phosphate esters produced by the action of phosphotransferases can have their phospho groups transferred without inversion to 1,2-propanediol and the chirality can be determined by this method. 

Exercise 31-1 If the ferrocene rings in 3 were not free to rotate, how many different dichloroferrocene isomers would be expected (including chiral forms) How could the substitution method (Section 1-1F) be used to determine which of the isomers was which ... 

A number of fine studies have shown that high ee s can be achieved. It has generally proven feasible to determine the resultant chiral form from the chiral conformation of the reactant molecules in the crystal. Generally the optical product closest in geometry to the chiral reactant is the true final stereoisomer. Examples of this, 13 and 14, illustrate schematically the chiral conformation of the reactants and the chiral form of the products. Some recent studies include those in reference 36. 

Perhaps one of the most important applications of chiral induction is in the area of liquid crystals. Upon addition of a wide range of appropriate chiral compounds, the achiral nematic, smectic C, and discotic phases are converted into the chiral cholesteric (or twisted nematic), the ferroelectric smectic C and the chiral discotic phases. As a first example, we take the induction of chirality in the columns of aromatic chromophores present in some liquid-crystalline polymers. " The polymers, achiral polyesters incorporating triphenylene moieties, display discotic mesophases, which upon doping with chiral electron acceptors based on tetranitro-9-fluorene, form chiral discotic phases in which the chirality is determined by the dopant. These conclusions were reached on the basis of CD spectra in which strong Cotton effects were observed. Interestingly, the chiral dopants were unable to dramatically influence the chiral winding of triphenylene polymers that already incorporated ste-reogenic centers. 

Multinuclear NMR studies revealed the presence of only a single diastereomer (A or A ) for reactions of EAC with the rhodium complex of the chiral ligand (S,S)-CHIRAPHOS. One might assume that the product chirality is determined by this preferred mode of substrate binding. This would be a form of "lock-and-key" mechanism that has its origins in Fischer s early concepts of enz)unatic stereospecificity. This assumption, however, is incorrect. The predominant enantiomer of the product is actually formed from the minor diastereomer of the catalyst— namely, olefin adduct A. 

The property of chirality is determined by molecular topology, and there are many molecules that are chiral even though they do not possess an asymmetrically substituted atom. Examples include certain allenes, spiranes, alkylidenecyclo-alkanes, and biaryls as well as other specific examples. Some specific molecules that have been isolated in optically active form are given in Scheme 2.2. The configuration of these molecules is established by subrules in the Cahn-Ingold-Prelog convention. We will not describe these here. Discussion of these rules can be found in Ref. 1. 

An important component of several asymmetric chemical reactions is diethyl tartrate, which is shown. Tartrate is obtained from grapes in chiral form. An enantiomer of diethyl tartrate, either (+) or (-), taken from one diastereomer can be used in the reaction, but the other diastereomer cannot be used. Draw both diastereomers of this molecule and determine which can be used in this... 

Where quantitative chiral purity determinations are required, the minimum level of detection for the minor component and accuracy achieved depend on factors which include the resolution between the resonances from the diastereoisomers formed and the signal-to-noise ratio in the spectrum. 

Depending on the absolute configuration of the chiral component in the aldol reaction, the prevailing enantiomer wiU be formed as a syn- or anft -product, depending on the structure of the enolate. The chiral component can be either one of the reactants or catalyst. In the first case we have non-catcdytic asymmetric aldol reaction, in the second a catalytic asymmetric aldol reaction. The configuration at the chiral center in the chiral component determines the direction of enantiose-lectivity. Both cases are discussed in the following sections. 

SWCNT, which is a one-dimensional (ID) system, can be considered as the conceptual rolling of a section of two-dimensional (2D) graphene sheet into a seamless cylinder forming the nanotube. The structure of SWCNT is uniquely described by two integers ( , m), which refer to the number of 5i and U2 unit vectors of the 2D graphene lattice that are contained in the chiral vector, = ndi + ma.2. The chiral vector determines whether the nanotube is a semiconductor, metal, or semimetal. From the (n, m) indices, one can calculate the nanotube diameter dt), the chirality or chiral angle (0), the electronic energy bands, and the density of electronic states. The nanotube diameter dt) determines the munber of carbon atoms in the... 

While one could require these conformations to satisfy a wide variety of geometric conditions by means of constraints on suitable polynomials in the interatomic squared distances and signed volumes, it turns out that the simplest possible such constraints are also the most widely useful. These are lower and upper bounds on the interatomic squared distances themselves, together with the signs (+1, —1, or 0) of the volumes of selected quadruples of atoms. The latter, called chirality constraints, determine the chirality of the quadruple, or force it to be planar if the sign is zero. The totality of constraints of this form is called a distance geometry description. Experience has shown that most conformation spaces of practical interest in chemical problems can be accurately described by means of these simple constraints alone. 

Ethyl (3R,5S)-dihydroxy-6-(benzyloxy)hexanoate 72 (Figure 11.1) is a key chiral intermediate for the s)mthesis of Atorvastatin 12, and Rosuvastatin 13, anticholesterol drugs that act by inhibiting HMG CoA reductase [132-134]. The enantioselective reduction of a diketone, ethyl 3,5-dioxo-6-(benzyloxy) hexanoate 73 to ethyl (3R,5S)-dihydroxy-6-(benzyloxy) hexanoate 72 (Figure 11.21) was demonstrated by cell suspensions of Acinetobacter calcoace-ticus sc 13876 [135,136]. On reduction of 73 by cell suspensions, the syn-4 and anti-8 dihydroxy esters were formed in the ratio of about 87 13, 83 17, 76 24 after 24 h at 2, 5 and 10 g/L of substrate input, respectively. There was no significant peak due to a monohydroxy ester. Chiral HPLC determined that the desired syn-(3R,5S)-72 was the major product wdth 99.4% ee. Almost complete (>95%) conversion of the diketoester 73 to dihydroxy ester 72 in 24 h... 

Alkenes or polyenes with isolated or coupled double bonds that are devoid of chiral atoms are not optically active. Such activity occurs in cyclic alkenes where double bonds occur in the trans form, such as in trans-cyclooctene (Figure 2.18). Another group of alkenes that includes representatives having optical activity is that of cumulenes. The name refers to cumulation of double bonds in such molecules. The best-characterized group of these compounds is that of allenes in which two double bonds occur next to each other [54]. Compounds of this type have a so-called chirality axis determined by cumulated double bonds. Besides allenes, higher optically active cumulenes are also known. An example of optically active cyclic allene is provided by 1,2-cyclononadiene, which was synthesized in 1972 [55]. 

The a-carbon of glutamic acid is chiral. A convenient and effective means to determine the chemical purity of MSG is measurement of its specific rotation. The specific optical rotation of a solution of 10 g MSG in 100 mL of 2 A/HQ is +25.16. Besides L-glutamic acid [56-86-0] D-glutamic acid [6893-26-1] and the racemic mixture, DL-glutamic acid [617-65-2] are known. Unique taste modifying characteristics are possessed only by the L-form. 

Two pathways were found for the chiral hydrogenation, and they give products with different stereochemistries (19). One pathway involves the preferred mode of initial binding of the reactant to the catalyst. The other pathway involves an isomer of the reactant—catalyst complex that is formed in only small amounts, but its conversion is energetically favorable and constitutes the kinetically predominant pathway to products (9) (Fig. 4). Thus the chirahty of the product is determined not by the preferred mode of the initial binding, but instead by the more favorable energetics of the pathway involving the minor isomer of the reactant—catalyst complex. 

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