Aryloxypropanoic acid

HSA bears structural and functional resemblance to BSA, and HSA-type CSPs [164] also show similar enantioselective binding preferences for acidic and neutral drug molecules, such as 2-aryloxypropanoic acids [165], warfarin [166] and benzodiazepines [167]. The chiral recognition mechanism of HSA has been the subject of a number of investigations [168], which revealed that enantioselective binding occurs primarily at two well-defined hydrophobic sites. Acidic drugs have been shown to bind preferentially to the so-called warfarin-azapropazone (site I) and neutral drugs to the indol-benzodiazepine site (site II). 

Solinas M, Gladiali S, Marchetti M (2005) Hydroformylation of aryloxy ethylenes by Rh/BINAPHOS complex - catalyst deactivation path and application to the asymmetric synthesis of 2-aryloxypropanoic acids. J Mol Catal A 226 141-147... 

Enantioenriched a-substituted carboxylic acids have been prepared using the growing cell system of Nocardia diaphanozonaria JCM3208. Racemic 2-aryl and 2-aryloxypropanoic acid could be deracemized leading to the recovery of the (R)-enantiomer in high yield (>50%) and 69% ee (Scheme 4.44). A new biocatalytic... 

The synthesis of (R)-a-aryloxypropanoic acid herbicides was achieved by involving the same chiral auxiliary with the corresponding trisubstituted phenoxides. The DKR, which gave in this case moderate diastereoselectivities, was followed by mild acid hydrolysis, as shown in Scheme 1.7. ... 

Derivatives of clofibric acid were used in earlier times as hyperlipidemia-controlling drugs. Currently more interest is shown in the synthesis of 2-methyl-2-aryloxypropanoic acids because these classes of compounds are being considered as possible remedies for type II diabetes. The earlier GSK process involves reacting 2-bromo-2-methylpropanoic acid with a phenolic compound at 50°C, where both compounds are suspended in 2-butanone solvent. The acid is expensive, and large volumes of the organic solvent are also required. 

Ammazzalorso A, Bettoni G, De Filippis B, Fantacuzzi M, Giampietro L, Giancristofaro A, Maccallini C, Re N, Amoroso R, Coletti C. Synthesis of 2-aryloxypropanoic acids analogues of clofihric acid and assignment of the absolute configuration by IH NMR spectroscopy and DFT calculations. Tetrahedron Asymm. 2008 19 989-997. 

A model for prediction of enantiopreference in the resolution of chiral acids is only published for C. rugosa lipase [16,17] (Fig. 1). This lipase shows high enantioselectivity toward many carboxylic acids, such as the commercial targets 2-arylpropanoic acids and 2-aryloxypropanoic acids, which fit the model. It appears, however, that when the large substituent is extensively branched the substrate no longer fits the model. 

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