Enantiomorph specification

Later, Pasteur 15) had arrived at the general stereochemical criterion for a chiral or dissymmetric molecular structure. Thus, the specific rotations of the two sets of sodium ammonium tartrate crystals in solution, isolated from the racemic mixture by hand-picking, were equal in magnitude and opposite in sign, from which Pasteur inferred that enantiomorphism of the dextro- and laevorotatory crystals is reproduced in the microscopic stereochemistry of the (+)- and (—)-tartaric acid molecules. The term dissymmetry or chirality is used when there is no superimposability between the two enantiomers, as seen in Sect. 2.1. 

M. phlei, and several strains of M. tuberculosis (28-30) contain a true asparaginase, as do extracts of Bacillus coagulans and Bacillus stearo-thermophilus (31). Brucella abortus contains two asparaginases, one specific for L-asparagine and the other for the opposite enantiomorph (32). An asparaginase is also present in Pseudomonas fluorescens (33). Also, Tsuji, in 1957, had reported the presence of asparaginase in extracts of acetone powders of E. coli, Staphylococcus, M. avium, and Aspergillus oryzae (34). 

Stereoisomeric specificity Only the l(-) enantiomorph of morphine and certain other opioids can interact with (enter) the receptor site. For example, levorphanol, a synthetic narcotic, is 5 to 10 times more potent than morphine, but its l(+) enantiomorph dextror-phan is devoid of analgesic activity. 

Neat isopropyl methylphosphinate (1) reacts exothermically on dropwise addition to methyl triflate to form a phosphonium salt (2), NMR 6 +73.4 (downfield from external H,P0.) J = 656 Hz, which yields isopropyl methyl methylphosphonite (3), when slowly added to a cold benzene solution containing excess tri-ethylamine (TEA). On warming to room temperature, the product was obtained as a benzene/TEA solution, which separated from a heavier liquid layer that consisted mainly of amine salt byproducts in benzene/TEA. When (R)-(+)-l (25% enantiomorphic excess) was used, a solution of (R)-(+)-3 (5 +176.6) was obtained in 60% yield, 90 mole-% pure with respect to its organophosphorus content. 2(Pie specific rotation of this product was calculated to be [a]D + 67.7 (c 2.6, benzene), if optically pure (+)-l starting material... 

The structure of this substance isolated from the somatic specific polysaccharide of M. tuberculosis28 was determined from the facts that the corresponding amide was the enantiomorph of 3,5-dimethyl-L-arabonamide (see below) and that by complete methylation followed by hydrolysis, oxidation and amide formation, 2,3,5-trimethyl-D-arabonam-ide was obtained. 

If one accepts the logic of seeking to deal with pure "single entity" drugs, should one also accept the proposal that drugs which undergo metabolic conversion should be avoided since, in effect, they behave as mixtures Such a decision would indeed disrupt our present armamentarium of useful drugs. The prohibition of racemates would also be disruptive, since there are still instances where therapy with a cheaper, easy-to-make racemate is fully as effective as with a more expensive specific enantiomorph. 

The two optically active acids have very low specific rotations (roughly, [a]i>d 4 ), but there appears to be ample evidence of their enantiomorphous relationship. Although the acids contain two asymmetric silicon groups, the specific rotations are only [a]i) 5 8 to 5 9 for the sodium salts. 

In a few cases, the space group cannot be determined uniquely from the symmetry of the reciprocal lattice and the systematic absences. In these cases, however, only a choice between two specific possibilities remains. The two choices are usually enantiomorphic space groups, such as P6 and P65. 

The fourteen alkaloids discussed in this section constitute a remarkable series of structurally and stereochemically interrelated substances. Superficially, all the alkaloids contain the same basic ring system, 5,10b-ethanophenanthridine (145), but alkaloids are elaborated from both enantiomorphs of this basic nucleus. Further variations are produced by differences in aromatic substitution and the functional groups attached to rings C.and D. It has been possible to interrelate all the alkaloids of this section through a combination of simple oxidation, reduction, and dehydration reactions coupled with four rather specific degradative techniques. These reactions are (1) aromatic demethoxylation by sodium and amyl alcohol (82), (2) replacement of OH by H via the action of lithium aluminum hydride on an intermediate chloro compound (146), (3) acid hydrolysis of ally lie methyl ethers to alcohols (147, 148), and (4) 0-methylation of hydroxylic alkaloids with... 

Hence, there can be four stereospecific polymerization mechanisms in primary polyinsertion, all of which have been documented with metallocene catalysts (Scheme 13) the two originated by the chiralities of the catalyst active sites, referred to as enantiomorphic site control (isospecific and syndio-specific site control), can be relatively strong, with differences in activation energy (AA. ) for the insertion of the two enantiofaces up to 5 kcal/mol. A value of 4.8 kcal/mol has been found by Zambelli and Bovey for a Ti-based heterogeneous catalyst. 

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