Chiral inversion

Whole microbial cells as well as microbially derived enzymes have played a significant role in the production of novel antibiotics. The potential of microorganisms as chemical catalysts, however, was first fully realized in the synthesis of industrially important steroids. These reactions have assumed increasing importance following the discovery that certain steroids such as hydrocortisone have anti-inflammatory activity, whilst derivatives of the steroidal sex hormones are nsefiil as oral contraceptive agents. More recently, chiral inversion of non-steroidal anti-inflammatory dmgs (NS AIDs) has been demonstrated. 

Hutt A.J., Kooloobandi A. Hanlon GW. (1993) Microbial metabolism of 2-arylpropionic acids Chiral inversion ofibuprofen and 2-phenylpropionic acid. Chirality, 5, 596-601. 

All evidence presented herein points to the generality of the 8 2 path for the surface add-catalyzed coupling of alcohols to ethers. The prc uct composition, the flow from reactants to products, and chirality inversion demonstrate convincingly that mechanistic patterns of the reaction including otygen retention, steric hindrances due... 

Ad(ii) On catalysts with pores and cavities of molecular dimensions, exemplified by mordenite and ZSM-5, shape selectivity provides constraints of the transition state on the S 2 path in either preventing axial attack as that of methyl oxonium by isobutanol in mordenite that has to "turn the comer" when switching the direction of fli t through the main channel to the perpendicular attack of methyl oxonium in the side-pocket, or singling out a selective approach from several possible ones as in the chiral inversion in ethanol/2-pentanol coupling in HZSM-5 (14). Both of these types of spatial constraints result in superior selectivities to similar reactions in solutions. 

Conclusive evidence has been presented that surface-catalyzed coupling of alcohols to ethers proceeds predominantly the S 2 pathway, in which product composition, oxygen retention, and chiral inversion is controlled 1 "competitive double parkir of reactant alcohols or by transition state shape selectivity. These two features afforded by the use of solid add catalysts result in selectivities that are superior to solution reactions. High resolution XPS data demonstrate that Brpnsted add centers activate the alcohols for ether synthesis over sulfonic add resins, and the reaction conditions in zeolites indicate that Brpnsted adds are active centers therein, too. Two different shape-selectivity effects on the alcohol coupling pathway were observed herein transition-state constraint in HZSM-5 and reactant approach constraint in H-mordenite. None of these effects is a molecular sieving of the reactant molecules in the main zeolite channels, as both methanol and isobutanol have dimensions smaller than the main channel diameters in ZSM-S and mordenite. 

Many nonsteroidal anti-inflammatory drugs (NSAIDs) are substituted 2-arylpropionic acids. Most NSAIDs also have a chiral carbon next to the carboxylate and are administered as a racemic mixture of the two enantiomers. In general, the (S)-enantiomcr is responsible for most of the antiinflammatory activity of these agents. It was found that the (/ -enantiomer is converted to the (S)-enantiomer but the reverse does not occur (23). As with amino acid conjugation, the pathway involves reaction with ATP to form an AMP ester, which is, in turn, converted to a Co-A ester, and it is the Co-A ester that undergoes chiral inversion (Fig. 7.14). Substrates include ibuprofen, naproxen, and fenoprofen. 

Wsol V, Skalova L, Szotakova B. Chiral inversion of drugs coincidence or principle Curr Drug Metab 2004 5(6) 517-533. 

A four-compartment model consisting of a two-compartment model for each enantiomer, with elimination from both compartments, connected by rate constants for chiral inversion was fitted to the concentration data, whereas the sedative effects were correlated with the blood concentrations of R- and S-thalidomide by means of logistic regression. PK modeling predicted that varying the infusion time of a fixed dose of S-thalidomide between 10 min and 6 h would have little influence on the maximal blood concentration of formed R-thaKdomide. These effects may chiefly be exerted by S-thalidomide, but the enantiomers are interconverted in vim... 

Xln, Y.-E, Zhou, X.-J., Cheng, X., and Wang, Y.-X. (2005). Renal D-amino acid oxidase mediates chiral inversion of N -nitro-D-arginine./. Pharmacol. Exp. Ther 312, 1090-1096. 

F and B NMR spectroscopy. The rate of propene polymerisation with this system was only three times faster than that of 1-hexene. This slow rate contributes to the high regioselectivity of the polymerisation no 2,1-propene misinsertions were detected. H and NMR spectroscopy also provided information about the chain termination mechanism here this occurred by p-H elimination in a first-order process. Polymer chain-end epimerisation, i.e. chirality inversion at the P-carbon of the polymer chain (Scheme 8.31), proceeded via a zirconium tert-alkyl (rather than tt-allyl) intermediate [96c]. 

Mandelic acid undergoes a chiral inversion, possibly by reversible oxidation to phenylglyoxylic acid. When -mandelic acid was administered, some 80% of the dose was recovered as phenylglyoxylic acid in 48 h with 16% as mandelic acid RJS 80 20). However, when racemic mandelic acid was given, 46% was excreted as phenylglyoxylic acid and 47% as i -mandelic acid. 

Naturally occurring compounds are usually single enantiomers, e.g. L-morphine, L-hyoscine. Atropine is an exception. Although synthesised in the belladonna plant as L-atropine, it is partly converted in the extraction process to the D isomer (chiral inversion), and is administered as a racemic mixture. During this process its OCHF,... 

Etodolac is a racemic acetic acid derivative with an intermediate half-life (Table 36-1). Etodolac does not undergo chiral inversion in the body. The dosage of etodolac is 200-400 mg three to four times daily. 

Amino acid conjugation of profen drugs leads to chiral inversion, as discussed in chapter 5. 

Figure 5.5 The mechanism of chiral inversion of ibuprofen and formation of hydrid triglycerides.

Chiral inversion of the (ft)-isomer to the active (S)-isomer occurs in vivo... 

Scheme 35 Metabolic chiral inversion of (R)-ibuprofen to the (S)-enantiomer.

The pharmacokinetics of the S(+) enantiomer were not influenced by the R(-) enantiomer. Furthermore, no R(—) enantiomer was detected after the administration of pure S(+) vigabatrin, thus demonstrating that no chiral inversion occurs in humans [63]. 

Tommy Eriksson, Sven Bjorkman, Bodil Roth, Asa Fyge, Peter Hoglund Stereospecific Determination, Chiral Inversion in vitro and Pharmacokinetics in Humans of the Enantiomers of Thalidomide, Chirality 7,44-52 (1995)... 

S. P. Jordan and V. H. Crespi, Theory of carbon nanocones mechanical chiral inversion of a micron-scale three-dimensional object, Phys. Rev. Lett. 93, 255504-1-4 (2004). 

This is a typical SN2 reaction (1) kinetics usually display clean second order (b) when the reagent is chiral, inversion of configuration occurs at the asymmetric carbon (71 ACS 18) when the alkylating reagent is tertiary (t-butyl iodide) or even secondary (i-Pr iodide), E2 elimination competes with aliphatic substitution (55JA1715 76AJC1745). 

Changing the conformation of a ring involves a chiral inversion and this can be achieved by reflecting all atoms of the ring through the plane defined by the cobalt atom and the two nitrogen atoms of the ring. 

Zhang L, Liu M (2009) Supramolecular chirality and chiral inversion of tetraphenylsulfonato porphyrin assemblies on optically active polylysine. J Phys Chem B 113 14015-14020... 

Racemic-to-Chiral Transformation and the Chirality Inversion Process in Cobaloxime Complex Crystals Only by Photoirradiation... 

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