Chiral Iminoesters Derived from d‑Glyceraldehyde in [3 + 2] Cycloaddition Reactions. Asymmetric Synthesis of a Key Intermediate in the Synthesis of Neuramidinase Inhibitors

Silver-catalyzed <i>endo</i>-selective and copper-catalyzed <i>exo</i>-selective asymmetric [3 + 2] cycloadditions of acrylates to chiral iminoesters derived from d-glyceraldehyde have been investigated. The reaction diastereoselectively provides highly functionalized pyrrolidines. This approach was used to develop the first asymmetric synthesis of a key intermediate in the synthesis of pyrrolidine influenza neuramidinase inhibitors

Chiral Iminoesters Derived from d‑Glyceraldehyde in [3 + 2] Cycloaddition Reactions. Asymmetric Synthesis of a Key Intermediate in the Synthesis of Neuramidinase Inhibitors

Silver-catalyzed <i>endo</i>-selective and copper-catalyzed <i>exo</i>-selective asymmetric [3 + 2] cycloadditions of acrylates to chiral iminoesters derived from d-glyceraldehyde have been investigated. The reaction diastereoselectively provides highly functionalized pyrrolidines. This approach was used to develop the first asymmetric synthesis of a key intermediate in the synthesis of pyrrolidine influenza neuramidinase inhibitors

Chiral Iminoesters Derived from d‑Glyceraldehyde in [3 + 2] Cycloaddition Reactions. Asymmetric Synthesis of a Key Intermediate in the Synthesis of Neuramidinase Inhibitors

Silver-catalyzed <i>endo</i>-selective and copper-catalyzed <i>exo</i>-selective asymmetric [3 + 2] cycloadditions of acrylates to chiral iminoesters derived from d-glyceraldehyde have been investigated. The reaction diastereoselectively provides highly functionalized pyrrolidines. This approach was used to develop the first asymmetric synthesis of a key intermediate in the synthesis of pyrrolidine influenza neuramidinase inhibitors

Improved Flavodoxin Inhibitors with Potential Therapeutic Effects against <i>Helicobacter pylori</i> Infection

<i>Helicobacter pylori</i> (<i>Hp</i>) infection affects one-half of the human population and produces a variety of diseases from peptic ulcer to cancer. Current eradication therapies achieve modest success rates (around 70%), resistance to the antibiotics of choice is on the rise, and vaccination has not proved to be successful yet. Using an essential <i>Hp</i> protein, flavodoxin, as target, we identified three low-molecular-weight flavodoxin inhibitors with bactericidal anti-<i>Hp</i> properties. To improve their therapeutic indexes, we have now identified and tested 123 related compounds. We have first tested similar compounds available. Then we have designed, synthesized, and tested novel variants for affinity to flavodoxin, MIC for <i>Hp</i>, cytotoxicity, and bactericidal effect. Some are novel bactericidal inhibitors with therapeutic indexes of 9, 38 and 12, significantly higher than those of their corresponding leads. Developing novel <i>Hp</i>-specific antibiotics will help fighting <i>Hp</i> resistance and may have the advantage of not generally perturbing the bacterial flora