Stereoselective Synthesis and Antiallodynic Activity of 3-Hydroxylated Paroxetines

The design, stereoselective synthesis and in vivo antiallodynic activity of four novel paroxetine analogs, named 3-hydroxy paroxetines (3HPXs), is reported herein. Among the novel synthesized compounds, three showed an antiallodynic effect, while (R,R)-3HPX was found to be 2.5 times more bioactive than (-)-paroxetine itself in neuropathic rats. Consequently, the current investigation not only discloses a novel promising analgesic drug, but also reveals that functionalization at the C3 position of paroxetine could be as effective as the common functionalization at either C4 or within the sesamol group.     

在OsO_4催化作用下烯烃的立体选择性氧化反应

四氧化锇是一种贵而毒性大的试剂。本文介绍催化剂量的四氧化锇在立体选择性高的烯烃氧化反应中的应用，为四氧化锇在有机合成中的应用，开辟了新的途径。     

4-羟基-5(4′-氯苯基)双环[4,4,0]-1-氮杂癸烷的合成

以 4′ 氯哌醋甲酯为原料,研究了作为潜在的治疗可卡因滥用症的药物———4 羟基- 5- (4′- 氯苯基 )双环 [4,4, 0]- 1 氮杂癸烷的合成。4′- 氯哌醋甲酯首先用乙酸酐在室温下进行乙酰基化,然后在 -70℃下经二异丙基胺锂(LDA)作用关环得中间产物(±)- threo -2, 4 -二氧代- 5- (4′- 氯苯基)双环[4, 4, 0] -1 氮杂癸烷,产率 60%。中间体先用硼氢化钠在甲醇中室温下选择性地将酮羰基还原,粗产物经V(石油醚)∶V(乙酸乙酯) =1∶1重结晶后,在四氢呋喃中于回流温度下用乙硼烷 四氢呋喃络合物进一步还原酰胺基,得到(±) threo 4α 羟基- 5 -(4′- 氯苯基 )双环[4, 4, 0]- 1 氮杂癸烷,两步产率为 67%。所得α位羟基产物经过Swern氧化,然后在四氢呋喃中在 -78℃下用三(仲丁基)硼氢化钾选择性还原,立体专一性地得到 (±) threo- 4β 羟基- 5 (4′- 氯苯基 )双环 [4, 4, 0]- 1 氮杂癸烷,氧化 还原反应总产率为 70%。     

五元环硫酸酯的合成及其在立体合成中的应用

五元环硫酸酯具有较高的反应活性，在有机合成中得到广泛的应用。本文将对五元环硫酸酯化合物的合成及其在有机立体合成中的应用作一综述。     

Production of (S)-β-Nitro Alcohols by Enantioselective C−C Bond Cleavage with an R-Selective Hydroxynitrile Lyase

Hydroxynitrile lyase (HNL)-catalysed stereoselective synthesis of β-nitro alcohols from aldehydes and nitroalkanes is considered an efficient biocatalytic approach. However, only one S-selective HNL—Hevea brasiliensis (HbHNL)—exists that is appropriate for the synthesis of (S)-β-nitro alcohols from the corresponding aldehydes. Further, synthesis catalysed by HbHNL is limited by low specific activity and moderate yields. We have prepared a number of (S)-β-nitro alcohols, by kinetic resolution with the aid of an R-selective HNL from Arabidopsis thaliana (AtHNL). Optimization of the reaction conditions for AtHNL-catalysed stereoselective C−C bond cleavage of racemic 2-nitro-1-phenylethanol (NPE) produced (S)-NPE (together with benzaldehyde and nitromethane, largely from the R enantiomer) in up to 99 % ee and with 47 % conversion. This is the fastest HNL-catalysed route known so far for the synthesis of a series of (S)-β-nitro alcohols. This approach widens the application of AtHNL for the synthesis not only of (R)- but also of (S)-β-nitro alcohols from the appropriate substrates. Without the need for the discovery of a new enzyme, but rather by use of a retro-Henry approach, it was used to generate a number of (S)-β-nitro alcohols by taking advantage of the substrate selectivity of AtHNL.     

β21S钛合金工艺塑性图

主要研究了β21S钛合金的工艺塑性图，制定了该合金的锻造工艺参数。通过该合金的工艺塑性图，确定变形温度为750-1050℃，最大变形量为75％－80％，终缎温度为700℃。从合金的工艺塑性角度来看，以上 数据是合理的。     

Stereoselective alternating copolymerization of aliphatic acetylenes with sulphur dioxide

A number of purified terminal aliphatic acetylenic hydrocarbons has been copolymerized with liquid sulphur dioxide in the presence of t-butyl hydroperoxide at low temperature. Benzoyl peroxide, hydrogen peroxide and m-chloroperbenzoic acid were ineffective. Neither sulphur dioxide nor t-butyl hydroperoxide alone was capable of polymerizing pure alkynes. Aged (impure) alkynes were copolymerized with sulphur dioxide in the absence of t-butyl hydroperoxide. All resulting alkyne-SO₂ copolymers were alternating with 100% trans configuration regardless of the nature of the alkyne, the solvent, or temperature. Several studies were performed to characterize the polysulphones, such as infra-red spectroscopy, ¹H and ¹³C nuclear magnetic resonance spectroscopy, melting point, viscosity, elemental analysis, solubility, film formation and flammability. A mechanism is proposed in which sulphur dioxide homolytically decomposes the organic hydroperoxide into free radicals which initiate the polymerization. The alkyne-SO₂ charge transfer complex is formed in solution, and the initiation and propagation steps probably involve this complex in equilbrium with its monomers.     

Optical isomers of 3,13-dimethylheptadecane: Sex pheromone components of the western false hemlock looper,Nepytia freemani (Lepidoptera: Geometridae)

(3S, 13R)-3, 13-Dimethylheptadecane [(3S, 13R)-3, 13-dime-17Hy] is the major pheromone component of the western false hemlock looper (WFHL),Nepytia freemani. In comparative gas chromotographic-electroantennographic detection (GC-EAD) analyses of stereoselectively synthesized isomers, 1 pg of (3S, 13R)-dime-17Hy elicited significantly stronger electrophysiological responses by male WFHL antennae than did 1 pg of separately injected (3R, 13R)-, (3R, 13S)- or (3S, 13S)-3, 13-dime-17Hy. In field experiments with individually tested stereoisomers. (3S, 13R)-3, 13-dime-17Hy was the only stereoisomer to attract males, but the four-stereoisomer blend was 3.6 times more attractive. Quaternary and all binary combinations of (3S, 13R)-3, 13-dime-17Hy with the other stereoisomers were equally attractive, suggesting that synergisytic behavioral activity in WFHL resided with either one of (3R, 13R)-, (3R, 13S)-, or (3S, 13S)-3, 13-dime-17Hy. Because optical isomers of (di)methylhydrocarbons do not separate on currently available columns, it remains unknown whether female WFHL also produce a four-stereoisomer pheromone blend. Substitutionality of pheromone stereoisomers without loss of behavioural activity has not previously been reported, but favorably compares with the concept of pheromone redundancy that was first suggested for the multiple pheromone component blend of the cabbage looper moth,Trichoplusia ni.     

辣椒碱的合成研究进展

辣椒碱广泛应用于医药、农药等领域。本文综述了辣椒碱的合成研究进展,指出了辣椒碱合成研究中存在的主要问题一一如何立体选择性地合成出反式双键,以及烯烃的顺式结构转变为反式结构的异构化反应。最后展望了辣椒碱合成研究的发展方向。     

Correlation of the Extent of Fjord-Region Oxidation with DNA Binding and Mutagenicity of the Enantiomeric 11,12-Dihydrodiols of Dibenzo[a,l]pyrene

In vitro studies on the hepatic biotransformation of the enantiomeric trans-11,12-dihydrodiols of dibenzo[a,l]pyrene (DB[a,l]P) using microsomal fractions of animals pretreated with Aroclor 1254 revealed that the formation of fjord-region dihydrodiol epoxides strongly depends on the absolute configuration of the substrate. Both the (-)-11R,12R- and the (+)-11S,12S-enantiomer are converted diastereoselectively to the (-)- and (+)-anti-dihydrodiol epoxide, respectively, by either rat or mouse liver microsomes. Fjord-region oxidation occurs to greatest extent on incubation of the (-)-11R,12R-dihydrodiol with preparations from rats. This finding is in line with the differences seen for the two enantiomers on the total DNA binding under identical activation conditions as well as on the mutagenic activity in Chinese hamster V79 cells using the postmitochondrial hepatic fraction of Aroclor 1254-treated rats as metabolizing system.