1999 antibiotics

antibioticsU 1200

43 - 264Synthesis and Antibacterial Properties of β-Diketone AcrylateBioisosteres of Pseudomonic Acid A. — Fourteen bioisosteres like (V)and (IX) are synthesized and evaluated for their antibacterial activities. Thefirst synthesis of the diketone system (V) uses a base-catalyzed deconjugationprocess. The second synthesis of system (IX) is complementary to that ofsystem (V) and the ready availability of aldehydes (VII) makes this synthesisthe preferred sequence. Optimal activity is observed with small para-phenylsubstituents as in (Va) and (IXa). Furthermore, the ring is not necessarilyaromatic, cf. (IXb). However, the antibacterial activity of (Vb) with an alkylchain is poor. — (BENNETT, ISOBEL; BROOM, NIGEL J. P.; CASSELS,ROBERT; ELDER, JOHN S.; MASSON, NICKY D.; O’HANLON, PETERJ.; Bioorg. Med. Chem. Lett. 9 (1999) 13, 1847-1852; SmithKline BeechamPharm., New Front. Sci. Park, Harlow, Essex CM19 5AW, UK; EN)

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