R enantiomers

The SHG/SFG technique is not restricted to interface spectroscopy of the delocalized electronic states of solids. It is also a powerful tool for spectroscopy of electronic transitions in molecules. Figure Bl.5.13 presents such an example for a monolayer of the R-enantiomer of the molecule 2,2 -dihydroxyl-l,l -binaphthyl, (R)-BN, at the air/water interface [ ]. The spectra reveal two-photon resonance features near wavelengths of 332 and 340 mu that are assigned to the two lowest exciton-split transitions in the naphtli-2-ol... 

Recently Desimoni et used the same bis(oxazoline) ligand in the magnesium(II) catalysed Diels-Alder reaction of the N-acyloxazolidinone depicted in Scheme 3.4. In dichloromethane a modest preference was observed for the formation of the S-enantiomer. Interestingly, upon addition of two equivalents of water, the R-enantiomer was obtained in excess. This remarkable observation was interpreted in terms of a change from tetrahedral to octahedral coordination upon the introduction of the strongly coordinating water molecules. 

When the lowest ranked substituent (the methyl group) is away from us the order of decreasing precedence of the remaining groups must appear in a clockwise sense in the R enantiomer... 

The reaction is reversible and its stereochemical requirements are so pronounced that neither the cis isomer of fumaric acid (maleic acid) nor the R enantiomer of malic acid can serve as a substrate for the fumarase catalyzed hydration-dehydration equilibrium... 

Arnygdabn a substance present in peach plum and almond pits is a denvative of the R enantiomer of benzaldehyde cyanohydrin Give the structure of (/ ) benzaldehyde cyanohydrin... 

In common with the naturally occurring carbapenem thienamycin (2), the introduction of the /n j -6-[l-(R)-hydroxyethyi] group had a profound effect on the biological properties of the penems. This, together with an indication from an early study (93) that, as with other P-lactams, the 5(R)-enantiomer was solely responsible for antibacterial activity, provided impetus for the development of methods for the synthesis of chiral penems. 

Tocainide. Tocainide is a po active primary amine analogue of lidocaine. It consists of the (3)-(—) and the more active (R)-(+) enantiomers. 

Tocainide is rapidly and well absorbed from the GI tract and undergoes very fitde hepatic first-pass metabolism. Unlike lidocaine which is - 30% bioavailable, tocainide s availability approaches 100% of the administered dose. Eood delays absorption and decreases plasma levels but does not affect bio availability. Less than 10% of the dmg is bound to plasma proteins. Therapeutic plasma concentrations are 3—9 jig/mL. Toxic plasma levels are >10 fig/mL. Peak plasma concentrations are achieved in 0.5—2 h. About 30—40% of tocainide is metabolized in the fiver by deamination and glucuronidation to inactive metabolites. The metabolism is stereoselective and the steady-state plasma concentration of the (3)-(—) enantiomer is about four times that of the (R)-(+) enantiomer. About 50% of the tocainide dose is efirninated by the kidneys unchanged, and the rest is efirninated as metabolites. The elimination half-life of tocainide is about 15 h, and is prolonged in patients with renal disease (1,2,23). 

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]. 

Fig. 3-1. Separation of racemic 3,5-dinitrobenzamido leucine Al.A -diallylamide on silica and polymer-based chiral stationary phases. Conditions column size 150 x 4.6 mm i.d. mobile phase 20 % hexane in dichloromethane flowrate 1 mL min injection 7 pg. Peaks shown are l,3,5-tri-rert.-butylbenzene (1), R-enantiomer (2) 5-enantiomer (2 ). (Reprinted with permission from ref. [8]. Copyright 1997 American Chemical Society.)...

Divalent sulfur compounds are achiral, but trivalent sulfur compounds called sulfonium stilts (R3S+) can be chiral. Like phosphines, sulfonium salts undergo relatively slow inversion, so chiral sulfonium salts are configurationally stable and can be isolated. The best known example is the coenzyme 5-adenosylmethionine, the so-called biological methyl donor, which is involved in many metabolic pathways as a source of CH3 groups. (The S" in the name S-adenosylmethionine stands for sulfur and means that the adeno-syl group is attached to the sulfur atom of methionine.) The molecule has S stereochemistry at sulfur ana is configurationally stable for several days at room temperature. Jts R enantiomer is also known but has no biological activity. 

The S enantiomer of ibuprofen soothes the aches and pains of athletic injuries much more effectively than the R enantiomer. 

Draw the R enantiomer of the reactant, and then change the configuration of the chirality center while replacing the Br with a CN. 

One of the most important reasons for using tosylates in S j2 reactions is stereochemical. The S]s]2 reaction of an alcohol via an alkyl halide proceeds with hvo inversions of configuration—one to make the halide from the alcohol and one to substitute the halide—and yields a product with the same stereochemistry as the starting alcohol. The SN2 reaction of an alcohol via a tosylate, however, proceeds with only one inversion and yields a product of opposite stereochemistry to the starting alcohol. Figure 17.5 shows a series of reactions on the R enantiomer of 2-octanol that illustrates these stereochemical relationships. 

The synthesis of an a-amino acid from an achiral precursor by any of the methods described in the previous section yields a racemic mixture, with equal amounts of S and R enantiomers. To use an amino acid in the laboratory synthesis of a naturally occurring protein, however, the pure S enantiomer must be obtained. 

An efficient kinetic resolution of racemic secondary allyl carbamates was accomplished by the jw-butyllithium-(-)-sparteine complex76 131. Whereas the R-enantiomer (80% ee) is recovered unchanged, the 5-enantiomer is deprotonated preferentially. 

R)- and (S)-2-I Iydroxy-1.2,2-triphenylcthyl acetate are commercially available from Merck, Darmstadt, Germany and from Newport Pharmaceuticals, Ireland. The (R)-enantiomer is also available from Fluka and Chiron. 

R)-Enantiomer predominates. When the reaction sequence is performed with the corresponding RAMP-hydrazone, (S)-l-(4-benzyloxy-3-melhoxyphenyl)-5-hydroxy-3-decanoneis obtained in 75% yield and 39% ee17. 

The Diels-Alder reaction of nonyl acrylate with cyclopentadiene was used to investigate the effect of homochiral surfactant 114 (Figure 4.5) on the enantioselectivity of the reaction [77]. Performing the reaction at room temperature in aqueous medium at pH 3 and in the presence of lithium chloride, a 2.2 1 mixture of endo/exo adducts was obtained with 75% yield. Only 15% of ee was observed, which compares well with the results quoted for Diels-Alder reactions in cyclodextrins [65d]. Only the endo addition was enantioselective and the R enantiomer was prevalent. This is the first reported aqueous chiral micellar catalysis of a Diels-Alder reaction. 

Efforts were also made to invert the sense of enantioselectivity in the hydrolytic kinetic resolution of ester (1) using PAL with preferential formation of (R)-2 [40,411-Using epPCR and DNA shuffling, an (R)-selective mutant showing an E value of 30 was evolved by screening about 45 000 clones for the (R) enantiomer. The best mutant is characterized by 11 mutations, which are different from those of the best (S)-selective variant X [41]. 

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