Discovery of Highly Potent Liver X Receptor β Agonists.

Introducing a uniquely substituted phenyl sulfone into a series of biphenyl imidazole liver X receptor (LXR) agonists afforded a dramatic potency improvement for induction of ATP binding cassette transporters, ABCA1 and ABCG1, in human whole blood. The agonist series demonstrated robust LXRβ activity (>70%) with low partial LXRα agonist activity (<25%) in cell assays, providing a window between desired blood cell ABCG1 gene induction in cynomolgus monkeys and modest elevation of plasma triglycerides for agonist . The addition of polarity to the phenyl sulfone also reduced binding to the plasma protein, human α-1-acid glycoprotein.

Small-molecule effectors of hepatitis B virus capsid assembly give insight into virus life cycle.

The relationship between the physical chemistry and biology of self-assembly is poorly understood, but it will be critical to quantitatively understand infection and for the design of antivirals that target virus genesis. Here we take advantage of heteroaryldihydropyrimidines (HAPs), which affect hepatitis B virus (HBV) assembly, to gain insight and correlate in vitro assembly with HBV replication in culture. Based on a low-resolution crystal structure of a capsid-HAP complex, a closely related series of HAPs were designed and synthesized.

Palladium-catalyzed cross-coupling of Baylis-Hillman acetate adducts with organosilanes.

[Reaction: see text]. A cross-coupling reaction between acetates of Baylis-Hillman adducts and organosilanes is described. A nonconventional solvent poly(ethylene glycol) (PEG) is used as the reaction medium.

Pd-catalyzed cross-coupling of Baylis-Hillman acetate adducts with bis(pinacolato)diboron: an efficient route to functionalized allyl borates.

The cross-coupling of Baylis-Hillman acetate adducts and bis(pinacolato)diboron proceeds readily in high yields in the presence of palladium catalyst to produce 3-substituted-2-alkoxycarbonyl allylboronates. These allylboronates can be transformed to stable allyl trifluoroborate salts by addition of excess aqueous KHF2. Both the allylboronate and allyltrifluoroborate derivatives react with aldehydes to afford functionalized homoallylic alcohols stereoselectively.

Palladium-catalyzed cross-coupling of acetates of Baylis-Hillman adducts and potassium organotrifluoroborates.

[reaction: see text] The cross-coupling of potassium organotrifluoroborates and acetates of Baylis-Hillman adducts proceeds readily in moderate to excellent yield in the presence of Pd(OAc)(2). The reaction tolerates hindered trifluoroborate salts, and the process is stereoselective.

Jatrophenone, a novel macrocyclic bioactive diterpene from Jatropha gossypifolia.

A novel macrocyclic diterpene, jatrophenone, has been isolated from the whole plant of Jatropha gossypifolia. The structure of the compound was established by detailed studies of its one- and two-dimensional (1D and 2D) NMR spectra. The compound possesses significant antibacterial activity.

Rhodium-catalyzed cross-coupling of allyl alcohols with aryl- and vinylboronic acids in ionic liquids.

[reaction: see text] The direct coupling of aryl- and vinylboronic acids with allylic alcohols has been achieved in ionic liquids using a rhodium catalyst.