Cascade reactions leading to the mechanism of action of vinaxanthone and xanthofulvin,natural products that drive nerve repair

The natural products vinaxanthone and xanthofulvin promote regeneration in animal models of spinal cord injury and corneal transplant. However, inhibition of the initially described biological target of these compounds, semaphorin 3A, does not fully account for the recovery demonstrated in vivo following administration of the natural products. Through chemical synthesis substantial quantities of both natural products have been accessed with early reaction development paving the way for synthesizing both compounds. The success of a model system, first disclosed herein, translated to the syntheses of both natural products. Following from this we also report for the first time the discovery of a new target of the natural products, the succinate receptor 1 (SUCNR1). Both natural products function as positive allosteric modulators of SUCNR1. As the first known allosteric modulators of SUCNR1, the compounds represent powerful new tools to understand the pharmacology of SUCNR1 and its control of growth and cellular defense.     

Chiral Atropisomeric Indenocorannulene Bowls: Critique of the Cahn–Ingold–Prelog Conception of Molecular Chirality

Chiral corannulenes abound, but suffer generally from configurational lability associated with bowl‐to‐bowl inversion, 1 thus obviating questions of stereogenicity and stereoelement construction. 2 In contrast, peri‐annulated corannulenes show greatly increased barriers for bowl‐to‐bowl inversion; specifically indenocorannulenes invert on a time scale too slow to observe by normal NMR methods and raise the possibility of creating chiral atropisomeric bowl‐shaped aromatics. 3 Two methods for preparing indenocorannulene from simple 2‐haloarylcorannulenes—silyl cation C–F activation, 4 and Pd‐mediated C–Cl activation^[5]—enable the synthesis of an array of such chiral atropisomeric indenocorannulenes. 6 Resolution of the enantiomers by high‐performance liquid chromatography over chiral support phases motivates the study of chiroptical properties, the assignment of absolute “Cartesian” configuration, and the assessment of configurational stability. 7 These studies bring into question any systematic assignment of nontrivial stereoelements (i.e. not the molecule in its entirety) and refute any assertion of congruence between “Cahn–Ingold–Prelog elements” and the physical or “Cartesian” basis of chirality.     

Untersuchungen on Thoriumoxid-Katalysatoren. II [8] Über den Einfluß Oberflächenchemischer Eigenschaften von ThO2− Katalysatoren auf die selektive Dehydratisierung von 2-Butanol

Studies on Thoria Catalysts. II. On the Influences of Surfacechemical Properties Tho₂-Catalysts on the Selective Dehydration of 2-Butanol Acid and basic properties as well as the interaction of 2-butanol with the surfaces of some ThO₂catalysts were studied. Sites of low acidity and basic sites of medium strength were found on the catalysts. After CO₂ adsorption we have shown by i.r. spectroscopy the formation of monodentate and bidentate carbonate as well as hydrocarbonate. There were indications of Lewis-type acid sites. Bands of alcoxide and carboxylate structure were observed in the i.r. spectra by interaction with 2-butanol and thoria. A mechanism is proposed for dehydration of 2-butanol.     

Untersuchungen an Nickeloxid-Mischkatalysatoren. I. Strukturelle Eigenschaften von NiO/SiO2-Katalysatoren

Studies on Nickel Oxide Mixed Catalysts. I. Structural Properties of NiO/SiO₂ Catalysts Structural properties of NiO/SiO₂ catalysts prepared by precipitation-deposition and impregnation have been investigated. A nickel-layer-silicate like structure is formed only in the precipitated catalysts showed infrared spectroscopic measurements. After thermal treatment at 723 K by means of magnetic measurements and reflectance spectroscopy besides Ni²⁺ ions in octahedral environment tetrahedral coordinated Ni²⁺ions were found. The part of tetrahedral coordinated Ni²⁺ ions is independent of the NiO-content up to 40 mole % NiO. Nickel oxide is formed above a content of 40 mole %. In the case of the impregnated catalysts nickel oxide cluster are formed on the surface after annealing at 723 K.     

Stereoselective syntheses of dihydroxerulin and xerulinic acid, anti-hypocholesterolemic dyes from the fungus Xerula melanotricha

The title compounds 2 and 3, which are inhibitors of the biosynthesis of cholesterol, were synthesized in a convergent and perfectly stereoselective manner. In the key step, bromobutenolide 6 (obtained from levulinic acid in two steps) was coupled with either of the novel bis(stannanes) trans,cis,trans-35 or trans,trans,trans-35 [each accessible from 3-(tributylstannyl)allyl alcohol (17) in four steps], giving gamma-alkylidenebutenolide trans,trans,trans-32. This compound was coupled with iododiyne 42 or the bromoenediynoate 44 leading to dihydroxerulin (2) and to the (trimethylsilylethyl)ester 45 of xerulinic acid, respectively. Deprotection of the latter provided totally synthetic xerulinic acid (3) for the first time.