Roger Xie

Discovery of oxazolo[4,5-b]pyridines and related heterocyclic analogs as novel SIRT1 activators

SIRT1 is an NAD(+)-dependent protein deacetylase that appears to produce beneficial effects on metabolic parameters such as glucose and insulin homeostasis. Activation of SIRT1 by resveratrol (1) has been shown to modulate insulin resistance, increase mitochondrial content and prolong survival in lower organisms and in mice on a high fat diet. Herein, we describe the identification and SAR of a series of oxazolo[4,5-b]pyridines as novel small molecule activators of SIRT1 which are structurally unrelated to and more potent than resveratrol.

Potent in vitro methicillin-resistant Staphylococcus aureus activity of 2-(1H-indol-3-yl)quinoline derivatives.

A novel structural class of antibacterials, 2-(1H-indol-3-yl)quinolines, effective against methicillin-resistant Staphylococcus aureus (MRSA), was discovered from a combinatorial library. A structure-activity relationship (SAR) study was conducted to determine the pharmacophore and increase the potency of these compounds. Compounds were prepared that had minimum inhibitory concentrations (MICs) < 1.0 microg/mL against MRSA and retained activity against two strains of glycopeptide intermediate-resistant S. aureus (GISA).

The synthesis of highly functionalized seven-membered allyl ethers using palladium-catalyzed alkoxyallylation of activated olefins and ring-closing olefin metathesis

The investigation of palladium-catalyzed alkoxyallylation of activated olefins, followed by ring-closing metathesis to synthesize functionalized seven-membered ring allyl ethers is described. The influence of the olefin substituents on the diastereoselectivity of the alkoxyallylation has also been examined.