The ruthenium-catalyzed reduction and reductive N-alkylation of secondary amides with hydrosilanes: practical synthesis of secondary and tertiary amines by judicious choice of hydrosilanes

A triruthenium cluster, (mu3,eta2,eta3,eta5-acenaphthylene)Ru3(CO)7 (1) catalyzes the reaction of secondary amides with hydrosilanes, yielding a mixture of secondary amines, tertiary amines, and silyl enamines. Production of secondary amines with complete selectivity is achieved by the use of higher concentration of the catalyst (3 mol %) and the use of bifunctional hydrosilanes such as 1,1,3,3-tetramethyldisiloxane. Acidic workup of the reaction mixture affords the corresponding ammonium salts, which can be treated with a base, providing a facile method for isolation of secondary amines with high purity. In contrast, tertiary amines are formed with high selectivity by using lower concentration of the catalyst (1 mol %) and polymeric hydrosiloxanes (PMHS) as reducing agent. Reduction with PMHS encapsulates the ruthenium catalyst and organic byproducts to the insoluble silicone resin. The two reaction manifolds are applicable to various secondary amides and are practical in that the procedures provide the desired secondary or tertiary amine as a single product. The product contaminated with only minimal amounts of ruthenium and silicon residues. On the basis of the products and observed side products as well as NMR studies a mechanistic scenario for the reaction is also described.     

Synthesis and Spectroscopic Properties of Phthalocyanine–[60]Fullerene Conjugates Connected Directly by Means of a Four‐Membered Ring

New covalently C₆₀‐conjugated phthalocyanine (Pc) analogues in which the Pc and C₆₀ components are connected by means of a four‐membered ring have been synthesized by taking advantage of a [2+2] cycloaddition reaction of C₆₀ with benzyne units generated from either a phthalocyanine derivative ( 8 ) or its precursor ( 1 ). The reaction of 1 with PhI(OAc)₂ and trifluoromethanesulfonic acid (TfOH) followed by the [2+2] cycloaddition of C₆₀ in the presence of tetra‐n‐butylammonium fluoride (TBAF) yielded the C₆₀‐substituted Pc precursor ( 3 ). Mixed condensation of 3 and 4,5‐dibutylsulfonylphthalonitrile ( 4 ) in a thermally promoted template reaction using a nickel salt successfully gave the Pc–C₆₀ conjugate ( 5 ). Results of mass spectrometry and ¹H and ¹³C NMR spectroscopy clearly indicate the formation of the anticipated Pc–C₆₀ conjugate. Direct coupling of C₆₀ with the Pc analogue that contained eight peripheral trimethylsilyl (TMS) groups ( 8 ) also proceeded successfully, such that mono and bis C₆₀‐adducts were detected by their mass, although the isolation of each derivative was difficult. The absorption and magnetic circular dichroism (MCD) spectra of 5 and the reference compound ( 7 ) differ from each other in the Q‐band region, thereby suggesting that the presence of the C₆₀ moiety affects the electronic structure of the conjugate. The reduction and oxidation potentials of 5 and 7 obtained by cyclic voltammetry are comparative, except for the C₆₀‐centered reduction couple at ?1.53 V versus Fc⁺/Fc in o‐dichlorobenzene (o‐DCB). A one‐electron reduction of 5 and 7 in tetrahydrofuran (THF) by using the sodium mirror technique results in the loss of band intensity in the Q‐band region, whereas the characteristic marker bands for Pc‐ring‐centered reduction appear at around 430, 600, and 900 nm for both compounds. The final spectral shapes of 5 and 7 upon the reduction resemble each other, thus indicating that no significant molecular orbital (MO) interactions between the C₆₀ and Pc units are present for the reduced species of 5 . In contrast, the oxidized species of 5 and 7 generated by the addition of NOBF₄ in CH₂Cl₂ show significantly different absorption spectra from each other. Whereas the broad bands at approximately 400–550 nm of 7 ⁺ are indicative of the cationic π‐radical species of metallo‐Pcs and can be assigned to a transition from a low‐lying MO to the half‐filled MO, no corresponding bands were observed for 5 ⁺. These spectral characteristics have been tentatively assigned to the delocalized occupied frontier MOs for 5 ⁺. The experimental results are broadly supported by DFT calculations.     

A new geranylated aromatic compound from the mushroom Hericium erinaceum

A new geranylated aromatic compound, 5-[(2'E)-3',7'-dimethyl-2',6'-octadienyl]-4-hydroxy-6-methoxy-1-isoindolinone (1), was isolated from the fruiting bodies of the mushroom Hericium erinaceum (Bull.: Fr.) Pers. (Hericiaceae) together with three known sterols, 5alpha,6alpha-epoxy-(22E)-ergosta-8(14),22-diene-3beta,7alpha-diol (2), (22E)-ergosta-7,9(11),22-triene-3beta,5alpha,6beta-triol (3) and (22E)-ergosta-7,22-diene-3beta,5alpha,6alpha,9alpha-tetrol (4). The structure of the new compound was elucidated on the basis of spectral data.     

Structure–Activity Studies on the Fluorescent Indicator in a Displacement Assay for the Screening of Small Molecules Binding to RNA

A series of xanthone and thioxanthone derivatives with aminoalkoxy substituents were synthesized as fluorescent indicators for a displacement assay in the study of small‐molecule–RNA interactions. The RNA‐binding properties of these molecules were investigated in terms of the improved binding selectivity to the loop region in the RNA secondary structure relative to 2,7‐bis(2‐aminoethoxy)xanthone (X2S) by fluorimetric titration and displacement assay. An 11‐mer double‐stranded RNA and a hairpin RNA mimicking the stem loop IIB of Rev response element (RRE) RNA of HIV‐1 mRNA were used. The X2S derivatives with longer aminoalkyl substituents showed a higher affinity to the double‐stranded RNA than the parent molecule. Introduction of a methyl group on the aminoethoxy moiety of X2S effectively modulated the selectivity to the RNA secondary structure. Methyl group substitution at the C1′ position suppressed the binding to the loop regions. Substitution with two methyl groups on the amino nitrogen atom resulted in reducing the affinity to the double‐stranded region by a factor of 40 %. The effect of methyl substitution on the amino nitrogen atom was also observed for a thioxanthone derivative. Titration experiments, however, suggested that thioxanthone derivatives showed a more prominent tendency of multiple binding to RNA than xanthone derivatives. The selectivity index calculated from the affinity to the double‐stranded and loop regions suggested that the N,N‐dimethyl derivative of X2S would be suitable for the screening of small molecules binding to RRE.     

Polystyrene-supported TBD catalyzed ring-opening of N-tosylaziridines with silylated nucleophiles

Polystyrene-supported TBD (PS-TBD) catalyzes the ring-opening of N-tosylaziridines with silylated nucleophiles to give the corresponding products in high yields. PS-TBD was easily recovered and reused without significant loss of catalytic activity.     

Anti-Obesity Effects of Matoa (Pometia pinnata) Fruit Peel Powder in High-Fat Diet-Fed Rats

Fruit peels, pericarps, or rinds are rich in phenolic/polyphenolic compounds with antioxidant properties and potentially beneficial effects against obesity and obesity-related non-communicable diseases. This study investigated the anti-obesity effects of matoa (Pometia pinnata) and salak (Salacca zalacca) fruit peel. Neither matoa peel powder (MPP) nor salak peel powder (SPP) affected the body weight, visceral fat weight, or serum glucose or lipid levels of Sprague–Dawley rats when included as 1% (w/w) of a high-fat diet (HFD). However, MPP significantly decreased the hepatic lipid level. MPP at a dose of 3% (w/w) of the HFD decreased body weight, visceral fat, and serum triglyceride levels as well as the hepatic lipid content. The inhibitory effect of MPP on hepatic lipid accumulation was not enhanced when its concentration was increased from 1% to 3% of the HFD. The anti-obesity effect of matoa was partly explained by the inhibitory effect of the matoa peel extract on fatty acid-induced secretion of ApoB-48 protein, a marker of intestinal chylomicrons, in differentiated Caco-2 cell monolayers. We identified hederagenin saponins that are abundant in MPP as potential anti-obesity substances. These results will contribute towards the development of functional foods with anti-obesity effects using the matoa fruit peel.     

Moment theory for the analytical determination of rate constants for solute permeation at the interface of spherical molecular aggregates

Moment equations were developed on the basis of the Einstein equation for diffusion and the random walk model to analytically determine the rate constant for the interfacial solute permeation from a bulk solvent into molecular aggregates (k_in) and the inverse rate constant from the molecular aggregates to the bulk solvent (k_out). The moment equations were in good agreement with those derived in a different manner. To demonstrate their effectiveness in one concrete example, the moment equations were used to analytically determine the values of k_in and k_out of three electrically neutral solutes, i.e. resorcinol, phenol, and nitrobenzene, from the first absolute (μ_1A) and second central (μ_2C) moments of their elution peaks, as measured by electrokinetic chromatography (EKC), in which the sodium dodecyl sulfate (SDS) micelles were used as a pseudostationary phase. The values of k_in and k_out should be determined with no chemical modifications and no physical action with the molecular aggregates because they are dynamic systems formed through weak interactions between the components. The moment analysis of the elution peak profiles measured by EKC is effective to unambiguously determine k_in, k_out, and the partition equilibrium constant (k_in/k_out) under appropriate experimental conditions.     

Absolute structure, biosynthesis, and anti-microtubule activity of phomopsidin, isolated from a marine-derived fungus Phomopsis sp.

The absolute configuration of phomopsidin, a marine-derived fungal metabolite from Phomopsis sp. isolated at Pohnpei, was determined by the exciton chirality method as 6S, 7S, 8S, 11S, 12R, and 15R. The biosynthetic study using ¹³C-labeled precursors revealed the origin of all carbon atoms in phomopsidin, which was built by nine acetates and three methyl groups from l-methionine. Inhibitory activities of phomopsidin and its Me ester derivative against microtubule assembly were examined together with the structurally related compounds MK8383, solanapyrones, and tanzawaic acids. Phomopsidin and its (16Z)-isomer (MK8383) showed anti-microtubule activity at IC₅₀ of 5.7 and 8.0 μM, respectively, while the Me ester and other compounds were not active at 100 μM.