关键词： (-)-石杉碱甲   不对称合成   乙酰胆碱酯酶抑制剂   手性二茂铁膦配体  

摘要： 目的　 (- ) 1 4 去甲基石杉碱甲的合成及其抑制乙酰胆碱酯酶活性研究。方法　从 β 酮酯 3与 2 亚甲基 1 ,3 丙二醇双醋酸酯 4在手性膦配体钯催化下 ,对映选择性的形成双环化合物 5 ,双键移位后得到关键中间体 6 ,进而复结晶富集后 ,得到光学纯 6。经Wittig反应 ,得双键化合物 7,酯基水解后 ,得到相应酸 8。经改良的Curtius重排 ,产生氨基甲酸酯 9。除去保护后 ,得目标化合物 2。结果　 (- ) 1 4 去甲基石杉碱甲仅是天然 (- ) 石杉碱甲抑制乙酰胆碱酯酶活性 1 8。结论　由电鳐乙酰胆碱酯酶与 (- ) 石杉碱甲复合物X 射线衍射结构分析揭示 ,1 4 甲基与酶形成氢键是 (- )

关键词： Oscillators (electronic)  

摘要： The properties of a system of two mutually synchronized coupled self-excited oscillators with respect to the symmetry criterion for various types of strong resistive coupling are considered. Power-frequency characteristics are analyzed for the stationary operating modes with power combining or subtraction. The results of the experimental investigation of a system with microwave self-excited oscillators are presented.

关键词： Salts   Crystallization   Crystal structure   Hydrophobicity   Hydrogenation  

摘要： An efficient and practical synthesis is presented of the pharmaceutically active MMP-3 inhibitor UK-370,106 (1) via an olefination/catalytic asymmetric hydrogenation sequence. Commercially available 5-bromo-2-iodotoluene was converted in two steps to the biarylpropanal equivalent (11), which was reacted with the phosphonosuccinate (10) to selectively afford the trans-b-substituted itaconate (12). Catalytic asymmetric hydrogenation of the itaconate (12) was achieved in good conversion and with 86-96% enantiomeric excess with a range of phosphine-modified rhodium and ruthenium cationic complexes. The resulting enantiomerically enriched 2-alkyl succinate (2) was elaborated to the desired drug substance (1) in two steps. The synthesis benefits from several crystalline intermediates, allowing control of process impurities, and can be operated safely within parameters readily achievable on scale. Investigations into the polymorphic forms of (1) have shown that the compound crystallizes in planar sheets, based on a backbone of hydrogen-bonding amide and acid functionalities, with large hydrophobic pockets formed by the biarylpropyl groups. An understanding of this crystal-packing arrangement has aided the development of crystallization processes allowing complete control over solid form.

关键词： DERIVATIVES   ALKYLATION   COMPLEXES   ANALOGS   GLYCINE   ALANINE  

摘要： The synthesis of enantiomerically pure non-proteinogenic his and cyclic amino acids 3a,b and achiral amino acid 3c using chiral Ni-II complex 1 and alpha,alpha'-dibromo-omicron-xylene as a bifunctional agent of alkylation is presented.

关键词： alkylation   alkynylation   allylic alkylation   asymmetric catalysis   binaphthyl   borane reduction   conjugate addition   ene-type cyclization   epoxidation   epoxide ring-opening   hetero-Diels-Alder reaction   hydroformylation   hydrogenation   octahydrobinaphthyl   ring-closing metathesis   trimethylsilylcyanation  

摘要： Although chiral binaphthyl-type ligands are already known to be effective over a broad spectrum of reactions, they sometimes fail in providing high enantioselectivities in some catalytic asymmetric reactions. This article summarizes recent attempts to elevate their performance by partly hydrogenating the naphthyl components of the binaphthyl. The synthetic routes to some of these ligands are briefly outlined. Positive results are observed in asymmetric hydrogenation, alkylation, borane reduction, epoxidation and hetero-Diels-Alder reactions. The function of the partially reduced binaphthyl skeleton, however, can sometimes be disadvantageous or ambiguous as illustrated in reactions such as asymmetric ring-closing metathesis, 1,4-conjugate addition, epoxidation, allylic alkylation, trimethylsilylcyanation, epoxide ring-opening and hydroformylation.

关键词： Palladium   Ethers   Anions   Sodium   Solution chemistry  

摘要： The title amine, an important substructure of nucleoside Q, is available from the 3,4-epoxycyclopentene in five steps. The epoxide is directly converted to the acetonide of cis-3, 4-dihydroxycyclopentene by treatment with boron trifluoride, a ring-opening with retention of configuration, a previously unknown process since known conversions of epoxides directly to acetonides normally involve initiating by nucleophilic opening of the epoxide with inversion of configuration. Two strategies were developed for diastereoselective allylic oxidation to cis-3,4-O-isopropylidenedioxy-trans-5-hydroxycyclopentene-direct oxidation with selenium dioxide and a two-step process, epoxidation followed by base. The corresponding carbonate undergoes a palladium-catalyzed deracemization with phthalimide as nucleophile in 98% ee. Recrystallization can increase the ee to > 99%. Removal of the phthalimide group to give the title compound occurs smoothly with ethylenediamine. Thus, a most efficient five-step synthesis (six steps from cyclopentadiene) contrasts with two recent asymmetric syntheses that required 12-16 steps.

摘要： The spontaneous resolution of conglomerates of a dibenzo analogue of Troger's base 1 and aziridine 2, as well as the second-order asymmetric transformation of (+/-)-1 into a single enantiomer were carried out for the first time.

关键词： stereochemistry   Boranes   slow regeneration   dimethyl sulfide   Scalability   Substrates   Asymmetric synthesis   Low temperature  

摘要： This report describes a scalable process for the asymmetric synthesis of (R)-2-aniino-1-(3-pyridinyl)ethanol dihydrochloride. The stereochemistry of the product is set via a reduction of 3-chloroacetyl pyridine with 2 equiv of borane-dimethyl sulfide and a catalytic amount of an in situ generated oxazaborolidine. The enantiomeric excess (ee) of the reductive step depends on the addition rate of the substrate and the temperature. The authors hypothesize that the low ee observed during a fast addition of the substrate or at low temperatures is due to the slow regeneration of the active catalyst from the catalyst-product complex.

关键词： .asymmetric synthesis  

摘要： The increasingly needed synthesis of both enantiomers of a chiral compound usually requires the use of both enantiomers of a chiral catalyst. Several of the usually employed chiral ligands are naturally available in only one enantiomeric form, the antipode often being of labor-intensive preparation. Enantiodivergent asymmetric catalysis has accrued in importance in this regard, in that it allows expeditious access to both enantiomers of a product without any direct modification on the chemical structure of the chiral promoter. Various promising examples will be discussed throughout the review. If available or envisageable, a mechanistic rationale for the observed enantioinversion will be outlined.

关键词： Resolving power   conglomerate   preparation   ligands   Asymmetric synthesis   X RAY STRUCTURE   enantiomers   Catalysis  

摘要： A practical synthesis of the atropisomerically chiral ligand QUINAP is described, followed by its efficient resolution into enantiomers by employing a deficiency of the chloropalladium complex derived from 1'-(R)-1'-(dimethylamino)-1-ethylnaphthalene. The X-ray structure of the ligand, which crystallises as a conglomerate, is reported.