关键词： 紫牡丹内酯   消旋合成   不对称合成   环氧重排  

摘要： 芍药属植物的根皮是传统中药，名为丹皮，具有清热凉血、活血化瘀的功效。从紫牡丹PaeoniadelavayiFranch.的根皮中分离得到的单萜化合物紫牡丹内酯paeonilide是一高度氧化的变异单萜化合物。紫牡丹内酯具有选择性地抑制PAF诱导的血小板聚集(IC50=8μg/ml)的活性，而对ADP或AA诱发的血小板聚集无抑制作用。由于紫牡丹内酯的强生理活性及其有趣的骨架类型，合成紫牡丹内酯从而进行深入的药物化学及生理活性研究具有较重要的意义。　　 本论文研究了紫牡丹内酯的全合成方法，完成了紫牡丹内酯的消旋合成及不对称合成研究工作，通过不对称合成研究确定了紫牡丹内酯的绝对构型，并对研究工作中发现的α，β-不饱和酮的环氧化产物的重排反应进行了研究。　　 第一章主要综述了近年来有关牡丹内酯类化合物以及具有2，8-二氧代双环[3，3，0]辛烷-3-酮亚结构单元天然产物的合成进展。　　 第二章采用间甲基苯酚为原料完成了紫牡丹内酯的消旋合成。其关键步骤为含酚醚衍生物的Birch还原及非共轭水解成酮反应，最终通过氧化切断的方法引入紫牡丹内酯所含有的关键含氧官能团(如Scheme1所示)。　　 第三章采用香芹酮R-(-)-carvone为原料完成了紫牡丹内酯的不对称合成，关键步骤为缩酮羰基的引入。1H-NMR、13C-NMR和IR数据尤其是比旋光证实合成产物与天然产物一致，从而确定了紫牡丹内酯的绝对构型为R构型(如Scheme2所示)。　　 第四章主要围绕α，β-不饱和酮邻位乙酰氧化的方法进行研究，对α，β-不饱和酮的环氧化合物在醋酸-无水醋酸钠条件下的重排反应进行了较系统的研究工作，并将这一重排反应成功应用到非甾体的双环及单环体系。　　 第五章为论文中相关化合物的合成及其谱图数据。

关键词： DOPA   ALKYLATION   SUCCINIMIDES   ISOQUINOLINE   CHEMICAL reactions   CHEMICAL processes  

摘要： Stereocontrolled intramolecular alpha-amidoalkylation reactions of L-DOPA-derived succinimides have been studied. Addition of MeLi to nonracemic succinimides 9a-d yields oxoamides, which are cyclized upon treatment with Lewis or protic acids to afford (5S, 10bS)-trans 11 or (5S,10bR)-cis 12 pyrroloisoquinolines with variable diastereoselectivities, but with high enantiomerical purities (ee 99%).

关键词： amines   asymmetric catalysis   asymmetric synthesis   imine coupling   niobium  

摘要： An efficient homocoupling of imines to give vicinal diamines promoted by low-valent niobium, generated by treatment of NbCl5 with zinc powder, is described. The desired products were obtained in good to excellent yields. Dihydroisoquinoline derivatives also gave the coupling products with good diastereoselectivities (D,L/meso). Optical resolution of the racemic octahydrobiisoquinolines was achieved and their complexes with Cut used in the catalytic asymmetric oxidative coupling of beta-naphthols. (c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.

关键词： ASYMMETRY (Chemistry)   CATALYSIS   ENANTIOMERS   ORGANIC compounds   STEREOISOMERS   ALCOHOL  

摘要： Catalytic asymmetric synthesis of the natural antibiotic fostriecin (CI-920) and its analogue 8-epifostriecin and evaluation of their biological activity are described. We used four catalytic asymmetric reactions to construct all of the chiral centers of fostriecin and 8-epi-fostriecin;cyanosilylation of a ketone, Yamamoto allylation, direct aldol reaction, and Noyori reduction, two of which were developed by our group. Catalytic enantioselective cyanosilylation of ketone 13 produced the chiral tetrasubstituted carbon at C-8. Both enantiomers of the product cyanohydrin were obtained with high enantioselectivity by switching the center metal of the catalyst from titanium to gadolinium. Yamamoto allylation constructed the C-5 chiral carbon in the alpha,beta-unsaturated lactone moiety. A direct catalytic asymmetric aldol reaction of an alkynyl ketone using LLB catalyst constructed the chirality at C-9 with the introduction of a synthetically versatile alkyne moiety, which was later converted to cis-vinyl iodide, the substrate for the subsequent Stille coupling for the triene synthesis. Noyori reduction produced the secondary alcohol at C-11 from the acetylene ketone 6 with excellent selectivity. Importantly, all the stereocenters were constructed under catalyst control in this synthesis. This strategy should be useful for rapid synthesis of stereoisomers of fostriecin.

关键词： 膦配体   手性催化剂   不对称氢化   应用研究   硅氢化  

摘要： 本文详细介绍了手性膦配体催化剂在不对称羰基化、芳基化、烷基化、硅氢化中的催化反应,并提出了研究手性膦配体催化剂的方向和存在的主要问题。

关键词： ENANTIOSELECTIVE catalysis   HETEROGENEOUS catalysis   ENANTIOMERS   HYDROXYLATION   CHEMICAL reactions   DIASTEREOISOMERS   OPTICAL isomers  

摘要： The enantioselective synthesis of anamarine has been achieved in 21 steps. The route relies on enantio- and regioselective Sharpless dihydroxylation of dienoate ester and zinc borohydride reduction to establish the C-8-C-11 stereochemistry. A diastereoselective Leighton allylation established the desired C-5 stereochemistry. The route has also been used to prepare two diastereoisomers of anamarine in 14 steps.

关键词： RNA   NUCLEIC acids   GENETIC regulation   BIOSYNTHESIS   GENE expression  

摘要： Recent discovery of RNA interference as an efficient and naturally occurring mechanism of gene regulation has reinvigorated the interest in chemically modified RNA. For potential in-vivo applications small interfering RNAs require chemical modifications to fine-tune the thermal stability and increase the cellular delivery and potency and in vivo half-life of the RNA duplexes. From this perspective, amides as neutral and hydrophobic internucleoside linkages in RNA are highly interesting modifications for RNA interference. Amides are remarkably good mimics of the phosphodiester backbone of RNA and can be prepared using a relatively straightforward peptide coupling chemistry. However, the progress in the field has been hampered by the shortage of efficient methods to synthesize the monomeric building blocks for such couplings, the nucleoside amino acid equivalents. Herein, we report enantioselective synthesis of 5'-azido X-carboxylic acid derivatives of all four natural ribonucleosides. The key transformations in our synthesis are a double asymmetric ene reaction and a stereoselective iodolactonization that form the basic carbon skeleton of the modified ribose. Standard nucleoside synthesis is followed by a short and highly efficient protecting group manipulation to give the enantiomerically pure (> 98%) title compounds in 9-10 steps and 15-19% overall yields starting from small achiral molecules. The present results are a significant improvement over our first-generation racemic synthesis and compare favorably with the previously reported synthesis from nucteoside and carbohydrate precursors.

关键词： BENZALDEHYDE   ORGANOFLUORINE compounds   FLUORINE compounds   FLUORINE   HALOGENS  

摘要： Asymmetric Syntheses of enantiopure trans-3,4-difluoropyrrolidines have been prepared by the introduction of fluorine at both centers in a single operation;asymmetric epoxidations and additions to benzaldehyde were conducted using catalysts whose chirality depends on organofluorine asymmetry.

关键词： Peptides and proteins   Genetics   Cyclization   Inhibitors   pH  

摘要： An efficient two-pot, asymmetric synthesis of benzothiadiazine-substituted tetramic acids is reported. Starting from commercially available a-amino acids or esters, reductive amination followed by a novel one-pot amide bond formation/Dieckmann cyclization provided the desired products in high yield and optical purity. An analogous solid-phase approach to the same targets is also presented. These compounds were found to be potent inhibitors of hepatitis C virus RNA-dependent RNA polymerase.