R isomers

Physical Properties. Mahc acid crystallines from aqueous solutions as white, translucent, anhydrous crystal. The S(—) isomer melts at 100-103°C (1) and the R(+) isomer at 98-99°C (2). On heating, D,L-mahc acid decomposes at ca 180°C by forming fumaric acid and maleic anhydride. Under normal conditions, malic acid is stable under conditions of high humidity, it is hygroscopic. 

The initial product is recrystalLized and filtered. The filtrate contains a 65% yield (99% ee) of the R-isomer. The crystals ate racemic (32% yield 8%... 

When ofloxacin was first introduced it was made available as the racemate. Later the optical isomers were prepared and it was found that the (3)-enantiomer, DR 3355 (6b), was substantially more active (8—128-fold) than the (R)-isomer against a broad range of bacteria (47—50). This chiral preference is not unique to ofloxacin and has been demonstrated in other quinolones as well (51,52). This significant finding has already had an impact on the design of new quinolone antibacterials still in development (53). 

Generally, these two methods complement each other. With some rare exceptions an enzyme that produces an S ester in the hydrolysis reaction produces an R isomer in acylation reaction and vice versa. 

Unprotected racemic amines can be resolved by enantioselective acylations with activated esters (110,111). This approach is based on the discovery that enantioselectivity of some enzymes strongly depends on the nature of the reaction medium. For example, the enantioselectivity factor (defined as the ratio of the initial rates for (3)- and (R)-isomers) of subtiHsin in the acylation of CX-methyl-ben zyl amine with tritiuoroethyl butyrate varies from 0.95 in toluene to 7.7 in 3-methyl-3-pentanol (110). The latter solvent has been used for enantioselective resolutions of a number of racemic amines (110). 

RS- P-Aminoisobutyric acid (a-methyl-P-alanine) [10569-72-9] M 103.1, m 176-178 , 178-180 , 181-182 , R -(-)- isomer [144-90-1] m 183 , [a] -21 (c 0.43, HjO), pKes,(,) 3.7, pKEst(2) 10.2. Colorless prisms from hot H O, were powdered and dried in vacuo. The purity is checked by paper chromatography (Whatman 1) using ninhydrin spray to visualise the amino acid Rp values in 95% MeOH and n-PrOH/5N HCOOH (8 2) are 0.36 and 0.50 respectively. [Kupiecki and Coon Biochem Prep 7 20 7960 Pollack J Am Chem Soc 65 1335 7943.] The R-enantiomer, isolated from iris bulbs or human urine was crystd from H2O and sublimed in vacuo [Asen et al. J Biol Chem 234 343 7959]. The RS-hydrochloride was recrystd from EtOH/Et20 m 128-129 , 130° [Bbhme et al. Chem Ber92 1258, 1260, 1261 7959]. 

Finally, it is necessary to select values for the thermodynamic constants that are to be used in equation (9). The data selected were that published by Beesley and Scott [2], for the two enantiomers, (S) and (R) 4-benzyl-2-oxazolidinone. The values for the standard free enthalpy and standard free entropy for the (R) isomer were... 

X R Isomer Time (days) Yield (%) anli/syn Ratio... 

Picenadol opioid analgesic (-r)-isomer (3.S,4R) p-receptor agonist (-)-isomer (3R.4.5) weak p-receptor antagonist... 

Prilocaine local anesthetic. S(-r)-isomer slowly hydrolyzed by amidase... 

R(-)-isomer rapidly hydrolyzed to toluidine (cause of methemoglobinemia)... 

R-isomer is cleared more rapidly in young males than young females or elderly of either sex... 

In the biphasic batch reaction the best reaction conditions were found for the system [EMIM][(CF3S02)2N]/compressed CO2. It was found that increasing the partial pressure of ethylene and decreasing the temperature helped to suppress the concurrent side reactions (isomerization and oligomerization), 58 % conversion of styrene (styrene/Ni = 1000/1) being achieved after 1 h under 40 bar of ethylene at 0 °C with 3-phenyl-1-butene being detected as the only product and with a 71 % ee of the R isomer. 

Alkylamines have a variety of applications in the chemical industry as starting materials for the preparation of insecticides and pharmaceuticals. Labetalol, for instance, a so-called /3-blocker used for the treatment of hi h blood pressure, is prepared by SN2 reaction of an epoxide with a primary amine. The substance marketed for drug use is a mixture of all four possible stereoisomers, but the biological activity derives primarily from the (R,R) isomer. 

As an example the enolatc of (5,)-2,5-dihydro-5-isopiopyl-3,6-diinethoxypyrazine, prepared from (S>valine and glycine, reacts with methyl (2s)-3-phenylpropenoate and the (2/ ,/ S)-iso-mer is obtained as the major diastereomer. The diastereofacial selectivity is reflected by a 2R/2S ratio of 99.6 0.4, whereas the high simple diastereoselectivity is shown by the diastereomeric ratio (syn/ami) of 91 9. Using methyl (Z)-3-phenylpropenoate the (2R, R)-isomer is formed... 

The hydrolysis of seven alkyl arenesulfinylalkanoates by the bacterium Corynebacterium equi IFO 3730 studied by Ohta and coworkers34 are recent examples of kinetic resolutions which give sulfoxides of high enantiomeric purity and in reasonable yield. Compounds 16a, 16b and 16c were recovered in 30 to 43% yield and in 90 to 97% e.e. The S enantiomers underwent hydrolysis more rapidly than the R isomers. Sulfoxide 17 was isolated in 22% yield and 96% e.e., but sulfoxide 18 was completely metabolized. Esters other than methyl gave inferior results. The acids formed upon hydrolysis, although detected, were for the most part further metabolized by the bacterium. 

We expect racemization in this reaction, since if we start with the pure (R) isomer, at first each exchange will produce an (S) isomer, but with increasing concentration of (S) isomer, it will begin to compete for 1 with the (/ ) isomer, until at the end a racemic mixture is left. The point investigated was a comparison of the rate of... 

Endotheiin A (ETa) receptor antagonist, Endotheiin A (ETa) receptor antagonist (R)-isomer, iCso = 5 nM... 

Due to the presence of the a-methyl groups, these agents exist as optical isomers. Both isomers usually produce DOM-like effects, and the R (-)isomers constitute the eutomeric series. In this regard then, the effects of these agents are stereoselective, but not stereospecific. In general, the R (-)isomers are twice as potent as their racemates and about 5 to 8 times more potent than their S (- )enantiomers. Some representative data are provided in table 1. 

Both optical isomers of AMPH are aetive (Seheehter 1978). In general, for the few isomeric pairs that have been examined, the S isomers of AMPH-like agents are slightly more potent than the raeemates and about 3 times more potent than the R isomers (Young and Glennon 1986). Y(-i-)AMPH, for example, is 3 times more potent than R(-)AMPH (table 2) 5 (-)cathinone is 2.5 times more potent than raeemie eathiione, but (unexpectedly) is nearly 15 times more potent than R(+)cathinone. 

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