2-aryloxy propionic acid

The enantiomerically pure tertiary bases dextro- and levomethorphan were used for the preparation of 2-aryloxy propionic acid derivatives 10 by increasing the selectivity dramatically based on the enantioselective inhibition of the slow reacting enantiomer. 

Biological target. (/ )-K-13675 is a 2-aryloxy-propionic acid derivative with specific agonist activity at the peroxisome prohferator-activated receptor a (PPARa), a transcription factor regulating lipid metabolism. 

Thus, compounds 5 and 6, two lead molecules within the class of hPPAR 2-aryloxy-3-phenyl propionic acid agonists, exhibit opposite enantiopreference for compound 1, the main object of our consideration in this chapter, which is also an 2-aryloxy-propionic acid derivative. Since, no details of the structure of the complex of 1 and the LBD of hPPARs were reported, it can be assumed that the absence of a phenyl group at position C(3) in 1 somehow results in inverse steric requirements for this agonist at LBD, when compared with its 3-phenyl congeners, 5 and 6. Since, the route to enantiomerically pure (R)-l includes a number of original synthetic solutions, a detailed discussion of these is presented in later sections. 

Recently, the potential of bacterial enzymes for the synthesis of aromatic, optically active amides, and carboxylic acids firom racemic nitriles was evaluated. An enantiomer-selective amidase, active on several 2-aryl and 2-aryloxy propionamides, was identifided and purified from Brevibacterium sp. strain R312 [145]. A nitrilase, found in Acinetobacter sp. strain AK226 and able to hydrolyze efihciently both aromatic and aliphatic nitriles, was reported to hydrolyze racemic nitriles to optically active 2-aryl propionic acids [146]. Enzyme system of Rhodococcus butanica could be successfully adapted for the kinetic resolution of a-arylpropionitriles resulting in the formation of (R)-... 

These compounds belong to the class of a-aryloxy-p-phenyl propionic acids, the first dual PPAR inhibitors with an aryloxy group on the a-carbon in relation to the carboxylic group, represented by the lead compotmd, (S)-5. 

Kobek K., Focke M. and LTchtenthaler H.K., 1988. Fatty acid biosynthesis and acetyl-GoA carboxylase as a target of diclofop, fenoxaprop and other aryloxy-phenoxy-propionic acid herbicides. Z. Naturforsch. 43c, 47-54 Kreuzaler F. and Hahlbrock K., 1975. Enzymic Synthesis of an aromatic ring from acetate units. Eur J. Biochem. 205-213. 

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