Rh(I)-Catalyzed 1,4-Conjugate Addition of Alkenylboronic Acids to a Cyclopentenone Useful for the Synthesis of Prostaglandins

An efficient and <i>trans</i>-diastereoselective Rh­(I)-catalyzed 1,4-conjugate addition reaction of alkenylboronic acids and a homochiral (<i>R</i>)-4-silyloxycyclopentenone useful for the synthesis of derivatives of prostaglandins E and F is described for the first time. The reaction functions under mild conditions and is particularly rapid (≤6 h) under low power (50 W) microwave irradiation at 30 °C in MeOH in the presence of a catalytic amount of KOH. Under these conditions, 3 mol % of [RhCl­(COD)]₂ is typically required to produce high yields. The method also functions without microwave irradiation at 3 °C in the presence of a stoichiometric amount of KOH. Under these conditions, only 1.5 mol % of [RhCl­(COD)]₂ is needed, but the reaction is considerably slower. The method accepts a range of aryl- and alkyl-substituted alkenylboronic acids, and its utility has been demonstrated by the synthesis of PGF_2α (dinoprost) and tafluprost

Enhanced Anti-influenza Agents Conjugated with Anti-inflammatory Activity

Influenza therapy with a single targeted compound is often limited in efficacy due to the rapidly developed drug resistance. Moreover, the uncontrolled virus-induced cytokines could cause the high mortality of human infected by H5N1 avian influenza virus. In this study, we explored the novel dual-targeted bifunctional anti-influenza drugs formed by conjugation with anti-inflammatory agents. In particular, the caffeic acid (CA)-bearing zanamivir (ZA) conjugates ZA-7-CA (<b>1</b>) and ZA-7-CA-amide (<b>7</b>) showed simultaneous inhibition of influenza virus neuraminidase and suppression of pro-inflammatory cytokines. These ZA conjugates provided remarkable protection of cells and mice against influenza infections. Intranasal administration of low dosage (<1.2 μmol/kg/day) of ZA conjugates exhibited much greater effect than the combination therapy with ZA and the anti-inflammatory agents in protection of the lethally infected mice by H1N1 or H5N1 influenza viruses