Phenylacetic acids, absolute configuration

Additionally, information about the absolute configuration of the analyte can be obtained from the sign of the chemical shift differences of the diastereomers. This will be discussed here. Use of other substituted phenylacetic acids fulfilling a similar purpose to Mosher s reagent will be described partly in this section and in the following one. 

The Mexican sponge Aplysina gerardogreeni contains calafianin (2106) (1880) (structure revised and confirmed by total synthesis, (1881-1883)), the known aerothionin, and the new phenylacetic acid 2107 (1880). These studies confirm that calafianin (2106) and aerothionin have the same absolute configuration (1883). Whereas aerothionin displays antibacterial activity against Mycobacterium tuberculosis, calafianin does not (1884). The Brazilian sponge Aplysina caissara contains the new caissarines A (2108) and B (2109) (1885). 

Another important example of the importance of chirality, related to rheumatology, is that shown by some members of the NSAID family of aryl acids. Certain molecules which inhibit prostaglandin synthetase in vitro show in vivo antiinflammatory actions. Such compounds include several families of acidic NSAIDs, particularly the aryl acids salicylates, indomethacin analogs, phenylacetic acids, fenamic acids and enolic compounds. With respect to the indomethacin analogs, an important characteristic has emerged, namely, the requirement for a sinister absolute configuration (the S form, which happens to be -t-) at the chiral centre. For these drugs the (5)-(-l-) enantiomers show dominant, if not exclusive, activity. ... 

A detailed n.m.r. method is now available for the determination of the absolute configuration of diastereomeric thiol esters. The observed chemical shift data of such esters of hydratropic acid (11) and other phenylacetic acids (12a and b) were found to differ significantly. Since the absolute configuration of hydratropic acid is known the absolute configuration of the thiols can be determined in a relatively simple way from the signs of the differences in signal positions of the constitutionally equivalent protons present. The method is applicable to mixtures of diastereoisomers and hence to the determination of enantiomeric purity. Boat conformations in the t-butylcyclohexanes (13a, b, and c) are caused by 1,3-diaxial interactions of the... 

Subsequent studies examined whether AMDase discriminates between two prochi-ral carboxyl groups. To this end, we prepared both enantiomers of a-methyl-a-phenylmalonate (6) with in one of the two carboxyl groups (Figure 3.7) [14], Starting from C-phenylacetate ( C-2), both enantiomers of chiral C-containing a-methyl-a-phenylmalonate (6) were prepared. The absolute configuration of the chiral substrate was clearly determined by the optical rotation of tire resolved hydroxyl acid (5). 

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