Direct asymmetric organocatalytic Michael reactions of alpha,alpha-disubstituted aldehydes with beta-nitrostyrenes for the synthesis of quaternary carbon-containing products

[reaction: see text] Direct asymmetric catalytic Michael reactions have been performed using chiral-amine/acid bifunctional catalysts. Performed with 0.3 equiv of (S)-(+)-1-(2-pyrrolidinylmethyl)pyrrolidine and 0.3 equiv of trifluoroacetic acid as the catalyst, the reaction of alpha,alpha-dialkylaldehydes with (E)-beta-nitrostyrene provided the alpha,alpha-dialkyl Michael products in up to 96% yield with up to 91% ee. With respect to enantioselectivity, l-proline was a poor catalyst of this class of Michael reactions.     

Polarized near-edge x-ray-absorption fine structure spectroscopy of C60-functionalized 11-amino-1-undecane thiol self-assembled monolayer: molecular orientation and evidence for C60 aggregation

Near-edge x-ray-absorption fine structure (NEXAFS) spectroscopy was adopted to probe the unoccupied electronic states of C60 anchored onto an organized assembly of 11-amino-1-undecane thiol on Au(111). The polarization dependence of the intensity of pi* resonance associated with C60 pi network revealed the self-assembled monolayer (SAM) system to be oriented with an average molecular tilt angle of 57 degrees with respect to the surface normal. Invoking the absence of solid-state band dispersion effects and in comparison to solid C60 and /or 1-ML C60/Au(111), the electronic structure of the resulting assembly was found dominated by spectral position shift and linewidth and intensity changes of the lowest unoccupied molecular orbital (LUMO), LUMO+1, and LUMO+2 orbitals. The latter implied hybridization between N Pz of -NH2 group of thiolate SAM and pi levels of C60, resulting in a nucleophilic addition with a change in the symmetry of C60 from Ih to C1 in the SAM. Occurrence of a new feature at 285.3 eV in the NEXAFS spectrum, assigned previously to pi* graphitic LUMO, signified the formation of aggregated clusters, (C60)n of C60 monomer. Low tunneling current scanning tunneling microscopy confirmed them to be spherical and stable aggregates with n approximately 5.     

飞行时间型质量分析器(TOFMS)的研制及应用

自行研制了电子碰撞离子化的飞行时间型质量分析器（ＴＯＦＭＳ），用于物质的化学分析。用研制的ＴＯＦＭＳ测量了Ａｒ离子化的飞行时间谱和离子的部分电离截面积比与碰撞电子能量的依赖关系，将它与Ｓｔｅｐｓｈａｎ等人的实验结果进行了比较。     

Direct synthesis of hetero-biaryl compounds containing an unprotected NH2 group via Suzuki-Miyaura reaction

Hetero-biaryl compounds were prepared via the Suzuki-Miyaura coupling reaction of hetero-aryl moieties containing an unprotected NH₂ group and arylboronic acids. D-t-BPF was found to be an efficient ligand for the cross-coupling of NH₂-unprotected hetero-aryl chlorides with phenylboronic acid.     

Imaging of enzyme activity by scanning electrochemical microscope equipped with a feedback control for substrate-probe distance

The enzymatic activity of diaphorase (Dp) immobilized on a solid substrate was characterized using a scanning electrochemical microscope (SECM) with shear force feedback to control the substrate-probe distance. The shear force between the substrate and the probe was monitored with a tuning fork-type quartz crystal and used as the feedback control to set the microelectrode probe close to the substrate surface. The sensitivity and the contrast of the SECM image were improved in the constant distance mode (distance, 50 nm) with the shear force feedback compared to the image in the constant height mode without the feedback. By using this system, the SECM and topographic images of the immobilized diaphorase were simultaneously measured. The microelectrode tip used in this study was ground aslant like a syringe needle in order to obtain the shaper topographic images. This shape was also effective for avoiding the interference during the diffusion of the enzyme substrates.     

A novel class of inhibitors for human steroid 5alpha-reductase: synthesis and biological evaluation of indole derivatives. II

In a search for novel nonsteroidal inhibitors of human prostatic 5alpha-reductase, we found a new series of indole derivatives that showed potent inhibitory activities for the human enzyme. Among them, 4-[(1-benzyl-1H-indol-5-yl)oxyl-3-chlorobenzoic acid (2d, YM-32906) showed more potent inhibitory activity than finasteride with an IC50 value of 0.44 nM. 3-Chloro-4-[[1-(4-phenoxybenzyl)-1H-indol-5-yl]oxy]benzoic acid (2m) showed inhibitory activities for both human and rat prostatic 5alpha-reductase with IC50 values of 2.1 and 73 nM, respectively. The synthesis and structure-activity relationships of these indole derivatives are presented.     

Practical synthesis of a neuropeptide Y antagonist via stereoselective addition to a ketene

[Reaction: see text]. The synthesis of neuropeptide Y antagonist 1, currently under clinical investigation for the treatment of obesity, is described. The convergent synthesis from trans-spirolactone carboxylic acid intermediate 2a and aminopyrazole 3 is predicated on a stereoselective route to the former. The coupling reaction of ethyl 4-oxocyclohexanecarboxylate (10a) with lithiated isonicotinamide 11 was investigated in detail, but even optimized conditions only provided a 45:55 ratio of trans:cis isomers (12a:12b). While selective crystallization schemes were developed to isolate the thermodynamically less stable trans isomer 2a, improved stereocontrol was subsequentially achieved by the application of ketene chemistry. The ketene formation and quench was investigated under a variety of conditions aimed at maximizing the trans:cis ratio. Reacting a mixture of carboxylic acids 2a and 2b with POCl3 in THF, followed by concomitant addition of tert-butyl alcohol in the presence of TMEDA at 35 degrees C provided a 4:1 ratio of trans:cis tert-butyl esters (18a:18b) via in situ ketene formation. Ester hydrolysis, followed by selective crystallization of undesired 2b as the HCl salt, led to isolation of 2a in 47% overall yield. Aminopyrazole intermediate 3 was synthesized via the condensation reaction of 2-fluorophenylhydrazine hydrochloride (4a) with acrylonitrile derivative 5 in 65-70% yield. Coupling of advanced intermediates 2a and 3b via activation with thionyl chloride gave a 92% yield of 1.     

Oxotitanium(IV) complexes of some bis‐unsymmetric Schiff bases: Synthesis,structural elucidation and biomedical applications

A number of oxotitanium(IV) complexes of the type TiOL with bis‐unsymmetric dibasic tetradentate Schiff base (LH₂) containing ONNO donor atoms have been synthesized. Mono‐Schiff base (OPD‐HNP) was prepared by the condensation of 1:3 molar ratio of 2‐hydroxy‐1‐naphthaldehyde (HNP) with o‐phenylenediamine (OPD). Dibasic unsymmetric tetradentate diamine Schiff bases were prepared by the reaction of OPD‐HNP with 2‐hydroxyacetophenone, 2‐hydroxypropeophenone, benzoylacetone, acetylacetone and ethylacetoacetate. Further, titanylacetylacetonate was reacted with these ligands to obtain their metal complexes. On the basis of analytical and physiochemical data, the formation of complexes as TiOL was suggested having square pyramidal geometry. Quantum mechanical approach also confirmed this geometry. The assessment of the synthesized ligands and their complexes showed that some behave as good inhibitors of mycelial growth against selected phytopathogic fungi but weak inhibitors against some selected bacteria. A few of them also showed antioxidant properties.     

Characterization of flower-inducing compound in Lemna paucicostata exposed to drought stress

A flower-inducing compound, LDS1, was isolated from a free-floating aquatic plant, Lemna paucicostata. The chemical structure and the absolute stereochemistry of LDS1 were determined as (9R,13R,11E,15Z)-9,13-dihydroxy-10-oxooctadeca-11,15-dienoic acid for its most abundant diastereomer. LDS1 was enzymatically produced when the plant was exposed to drought stress, and induced flowering at a concentration of 10 nM.