the material in its pure state but have confirmed its structure via its chemical reactions (vide infra). Thus the white sublimate, obtained upon treatment of 1,4-dimethoxyhexamethyl-p-disiline3 with acetyl chloride followed by removal of methyl acetate and excess acetyl chloride, was reconverted to 1,4-dimethoxyhexamethylp-disiline in an exothermic reaction with methanol and triethylamine. The dichloride was also prepared by Atwell.14 1,4-Dihydroxyhexamethyl-p-disiIine. Acetyl chloride (2 cm3) was heated to reflux overnight with 450 mg of 1,4-dimethoxyhexamethyhp-disiline. The excess acetyl chloride and methyl acetate were removed under vacuum.The residue was dissolved in 30 cm3 of dry tetrahydrofuran (distilled from LAH and used immediately). To this solution was added, with stirring, 0.5 cm3 of triethylamine (distilled from phenyl isocyanate) and 0.04 cm3 of water in 30 cm3 of dry THF. The mixture was allowed to stir overnight at room temperature. After the triethylamine hydrochloride was removed by filtration, the solvent was removed to afford the dihydroxide in quantitative yield. The white solid sublimes at 230°, is soluble in MeOH and DMSO, slightly soluble in ether, and insoluble in petroleum ether: mass spectrum (m/e) 228 (parent, 20%) 213 (M -15, 70%), 195 (50%), 173 (100%), 159 (80%), 119 (50%), 97,99 (20%), 75 (60%), 61 (20%), 45 (60%); nmr (DMSO-*, , external TMS) 0.05 (s, 6), 1.8 (s, 12), 3.4 (s, 1), 5.45 (s, 1). Therefore the dihydroxide exists as a 50/50 cis-trans mixture of isomers, where the difference in chemical shift between the isomeric hydroxyl hydrogens is ~2 ppm. Glpc (2-ft, 0.25-in. 10% SE-30 on silanized chromosorb W 30-60 mesh) showed two peaks of approximately equal intensity. Dodecamethyldioxa[l.l]di-p-disi!inocyclophane. Into a small, dry sublimer were placed 0.519 g of 1,4-dimethoxyhexamethyl-/> disiline and 1 cm3 of acetyl chloride. The mixture was heated to reflux overnight. The volatile components were then evaporated under a fast stream of dry argon gas and the residue was sublimed at 70°( 1 mm). The sublimer pot was exchanged quickly and the sublimate was washed into the new pot with 15 cm3 of dry THF.The THF solution was treated with 0.25 cm3 of hydrazine and allowed to sit for 48 hr. Upon evaporation of the solvent, the residue was washed several times with ether. The ether washings ( 14) W. H. Atwell, private communication.were stored at -15°o vernight and deposited 20-50 mg of colorless, hexagonal prisms (sublimation point >268°). The compound is slightly soluble in THF, DMSO, and ether and insoluble in petroleum ether. Glpc (2 ft X 0.25 in. column; 10% SE-30 on silanized chromosorb W 30-60 mesh; injection, 300°; column, 200°; detection, 300°) showed a single component. Elemental analysis was done via mass spectroscopy.15 Anal. Caled for C2OH30O2SÍ4: 420.1801. Found: 420.1792; error, 2 ppm. Nmr (CS2, S relative to TMS internal standard) 0.15 (s, 1), 1.7 (s, 2); ir (KBr) 2950, 1250, 1012, 850 cm"1.A dilute THF solution of freshly prepared 1,4-dichlorohexamethyl-p-disi...

Niemann-Pick type C (NPC) disease is predominantly caused by mutations in the NPC1 protein that affect intracellular cholesterol trafficking and cause accumulation of unesterified cholesterol and other lipids in lysosomal storage organelles. We report the use of a series of small molecule histone deacetylase (HDAC) inhibitors in tissue culture models of NPC human fibroblasts. Some HDAC inhibitors lead to a dramatic correction in the NPC phenotype in cells with either one or two copies of the NPC1 I1061T mutation, and for several of the inhibitors, correction is associated with increased expression of NPC1 protein. Increased NPC1 I1061T protein levels may partially account for the correction of the phenotype, because this mutant can promote cholesterol efflux if it is delivered to late endosomes and lysosomes. The HDAC inhibitor treatment is ineffective in an NPC2 mutant human fibroblast line. Analysis of the isoform selectivity of the compounds used implicates HDAC1 and/or HDAC2 as likely targets for the observed correction, although other HDACs may also play a role. LBH589 (panobinostat) is an orally available HDAC inhibitor that crosses the blood–brain barrier and is currently in phase III clinical trials for several types of cancer. It restores cholesterol homeostasis in cultured NPC1 mutant fibroblasts to almost normal levels within 72 h when used at 40 nM. The findings that HDAC inhibitors can correct cholesterol storage defects in human NPC1 mutant cells provide the potential basis for treatment options for NPC disease.

The direct reduction of arenes and heteroarenes by visible‐light irradiation remains challenging, as the energy of a single photon is not sufficient for breaking aromatic stabilization. Shown herein is that the energy accumulation of two visible‐light photons allows the dearomatization of arenes and heteroarenes. Mechanistic investigations confirm that the combination of energy‐transfer and electron‐transfer processes generates an arene radical anion, which is subsequently trapped by hydrogen‐atom transfer and finally protonated to form the dearomatized product. The photoreduction converts planar aromatic feedstock compounds into molecular skeletons that are of use in organic synthesis.

The palladium-catalyzed Suzuki-Miyaura cross-coupling reaction of organic halides with boronic acids is one of the most versatile methods for the synthesis of biaryls. Green chemistry is a rapidly developing new field that provides us a proactive avenue for the sustainable development of future science and technologies. When designed properly, clean chemical technology can be developed in water as a reaction medium. The technologies generated from such green chemistry endeavors may often be cheaper and more profitable. This review covers the literature on palladium-catalysed the Suzuki-Miyaura cross-coupling reaction in water.

Introduction of a biotinylated monophosphine palladium complex within streptavidin affords an enantioselective artificial Suzukiase. Site-directed mutagenesis allowed the optimization of the activity and the enantioselectivity of this artificial metalloenzyme. A variety of atropisomeric biaryls were produced in good yields and up to 90% ee.