No abstract

tives. -Flavones (III) are obtained from hydroxyacetophenones (I) utilizing the Baker-Venkataraman rearrangement, followed by microwave-assisted condensation. In several cases the diketones intermediates are purified by column chromatography, but in general it is convenient to use the crude compounds in the cyclization reaction. All of the eleven synthesized compounds exhibit antifungal activity against A.niger and F.oxysporium, and two of the flavonoid analogues, (IIIb) and (IIId), inhibit the growth of methicillin-resistant S.aureus. -(GHANI, S. B. A.; WEAVER, L.; ZIDAN, Z. H.; ALI, H. M.; KEEVIL, C. W.; BROWN*, R. C. D.; Bioorg. Med. Chem. Lett. 18 (2008) 2, 518-522; Sch. Chem., Univ. Southampton, Southampton SO17 1BJ, UK; Eng.) -H. Hoennerscheid 25-138

Two series of 0-aryl and N-aryl 0-ethyl phosphoramidates and phosphorodiamidates respectively containing a-amino acid ester moieties have been synthesized and characterized by 'H NMR, IR and mass spectroscopy. Stepwise multiple regression analysis showed that the anticholinesterase activity was strongly correlated with the chemical structures represented by the stereo-electronic and hydrophobic parameters with correlation coefficient of 0.999. These results revealed that the inhibition activity of both series was inversely correlated with the steric bulk of the p-aryl substituents and directly with the bulk of the alkyl groups of the amino acid moieties, whereas m-aryl substituents have no steric effect on the inhibition process. The inhibition was enhanced by strong n-electron acceptor aryl substituents and reduced by electron donating alkyl groups of the amino acids. This supported the proposed inhibition mechanism of nucleophilic attack of a hydroxyl group at the enzyme active site on the partially positive phosphorus atom in organophosphorus compounds. The inhibition was also increased by more hydrophilic substituents. These results showed the importance of both the reactivity of these compounds and their steric interaction with the A C E active site in controlling enzyme inhibition, in addition to the ease of more hydrophobic compounds to reach the enzyme active site.