关键词： 氟西汀   1,1\\\'\'-联二萘酚   Ti-BINOL   β-羟基-β-苯丙酸乙酯   不对称加成反应   不对称Reformatsky反应  

摘要： 氟西汀是目前临床广泛使用的一种非三环类抗抑郁药,除用于治疗抑郁症以外,氟西汀对临床常见的强迫症、贪食症、惊恐发作、经前期焦虑障碍等也有很好的疗效.由于它药效确切,副反应轻,上市后即受到青睐.年销售额已突破三十亿美元.药物手性化合物异构体在生理活性、药效、代谢行为等方面存在着明显差异,因此其对映体的不对称合成就得到了越来越多的关注.外消旋体拆分、不对称化学催化和酶催化都是制备氟西汀对映体的高效、简便的合成方法.我们尝试以手性1,1\'-联二萘酚为配体,通过不对称Reformatsky反应去合成制备氟西汀的重要中间体手性β-羟基-β-苯基丙酸乙酯,再经过一系列反应最终旨在合成手性药物氟西汀.利用反应物与产物在乙醇中溶解性能的差异,以50%乙醇溶液作溶剂合成了1,1\'-联二萘酚,并对合成工艺进行了优化和改进,得到了最佳的反应温度、时间及物料配比.实验操作简单,反应时间比较短,化学产率及纯度都较理想.将外消旋的1,1\'-联二萘酚与L-脯氨酸在苯中回流,重复三次实验操作,便可得到94%e.e.的拆分结果.实验操作简单,L-脯氨酸回收率较高,拆分成本降低.显然,在整个手性药物的合成中,第一步产物β-羟基-β-苯基丙酸乙酯的不对称合成是至关重要的.我们采用两种方法来完成,一是以化学计量的手性1,1\'一联二萘酚(BINOL)为配体,将对映选择性引入Reformatsky反应,二是采用手性催化剂Ti-BINOL,不对称催化有机锌试剂对羰基化合物的加成反应.产物经柱层析进一步分离提纯后,进行红外光谱、核磁共振氢谱、质谱分析表征,并与文献值相对照,可以确定产物为β-羟基-β-苯基丙酸乙酯.产物的构型及光学纯度在测试之中.

关键词： (-)-(2R,3S)-3-苯基-2,3-环氧丙酸甲酯   中间体   合成  

摘要： 以反式肉桂醇为原料,经Sharpless不对称环氧化,产生所需的两个手性碳(2S,3S)后,产物经氧化、酯化即得标题产 物(-)-(2R,3S)-3-苯基-2,3-环氧丙酸甲酯(1),三步总收率28.4％,所得产物的ee值>95％。

关键词： Friedlnder缩合反应   邻氨基苯甲醛   喹啉衍生物   杂环化学   不对称合成   药物合成  

摘要： 由于Friedl nder缩合反应通常是以邻氨基苯甲醛为原料与各种含α 氢的醛或酮发生缩合 ,其缩合反应应用于杂环化学、天然产物化学、药物化学、配位化学、金属有机化学、不对称有机合成化学等诸多研究领域 .综述了国内外Friedl nder缩合反应的研究进展近况 .

关键词： asymmetric synthesis   hydrazones   alkylation   amino alcohols   natural products  

摘要： The asymmetric synthesis of protected 2-amino-1,3-diols (S,R)-5 starting from 2,2-dimethyl-1, 3-dioxan-5-one is described. The stereogenic centres are generated by a-alkylation using the SAMP/RAMP hydrazone methodology and diastereoselective reduction of the ketones (S)-2 with L-selectride. The resulting alcohols (S,S)-3 are converted into the amines (S,R)-4 by nucleophilic substitution with sodium azide and subsequent reduction with lithium aluminium hydride. The products are obtained in high diastereomeric and enantiomeric excesses (de greater than or equal to 96%, ee = 90-94%). By employing this methodology, the ammonium salt of D-erythro-sphinganine (R,S)-11 was synthesised starting from RAMP-hydrazone (R)-1 in 47% overall yield and with excellent diastereomeric and enantiomeric excess (de, ee greater than or equal to 96%). ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).

关键词： 3-hydroxyproline   3-hydroxyproline betaines   reductive cyanation  

摘要： An improved three-steps method for the conversion of N-benzyl (S)-3-hydroxypyrrolidin-2-one 6 to (2S,3S)-3-hydroxyproline 1 is reported. The key step is the reductive cyanation of 6. The synthesis of 1 constitutes a formal asymmetric synthesis of (2S,3S)-3-hydroxyproline betaines 2.

关键词： asymmetric synthesis   chirality   solid-phase synthesis   substitution   sulfoximine  

摘要： An asymmetric synthesis of cycloalkenyl and alkenyloxiranes from allylic sulfoximines and aldehydes is described. Lithiation and titanation of cyclic and acyclic allylic sulfoximines with chlorotris(diethylamino)titanium and subsequent treatment with aldehydes gave, as described previously, enantio- and diastereomerically pure, syn-configured, sulfoximine-substituted homoallylic alcohols. Treatment of the sulfoximine-substituted homoallylic alcohols with chloroethyl chloroformate resulted in a facile substitution of the sulfoximine group by a Cl atom, with formation of the corresponding alkenyl chlorohydrins. In the case of the cycloalkenyl derivatives the substitution proceeded with high diastereoselectivities with retention of configuration, while in the case of the alkenyl derivatives, medium diastereoselectivities with inversion of configuration were observed. While elimination reactions of the cycloalkenyl chlorohydrins gave the corresponding enantio- and diastereomerically pure cis-configured cycloalkenyloxiranes in good overall yields, the alkenyl chlorohydrins afforded mixtures of enantiomerically pure trans and cis isomers in which the trans isomers dominated. The solution-phase synthesis was extended to the solid phase by the synthesis of an enantiomerically pure, polymer-bound allylic sulfoximine and its conversion into an alkenyloxirane. The initial results proved that the concept of the utilization of the sulfoximine group as a traceless chiral linker is feasible and suggest that the solid-phase asymmetric synthesis of cycloalkenyloxiranes by this route should be possible. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

关键词： asymmetric synthesis   enantioselectivity   chiral tether   chiral perturbation  

摘要： The 2,4-pentanediol (PD)-tethered reaction is a stereocontrolled reaction having versatile applicability. When reactant and reagent elements are connected through a PD tether prior to their reaction, stereochemical purity of the product is very high for nine different types of reactions so far studied. Selectivity of one of the reactions shows temperature independency over a wide range from -78 to 150 degreesC, which indicates that the stereocontrol is driven by the entropy term. The strict stereocontrol of this reaction at high temperatures can be extended to vapor phase reactions performed above 250 degreesC. To understand how the two methyl groups on the PD tether stereocontrol the reaction, a new parameter, a chiral perturbation factor, is introduced. By this analysis, it is disclosed that the methyl groups promote an activation entropy change for both the diastereomeric processes, and the strict stereocontrol is achieved when the changes have opposite signs. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).

关键词： 手性膦(磷)酸酯   手性膦(磷)酰胺   不对称合成   综述  

摘要： 讨论了手性膦 (磷 )酰胺及膦 (磷 )酸酯催化剂在不对称烷基化、不对称缩合、不对称氢化、不对称氰硅化等反应中应用的最新研究进展。参考文献 4 8篇。

关键词： 不对称合成   β—酮酯   微生物催化剂   金属手性催化剂   有机合成   催化氢化  

摘要： 不对称合成是当代有机合成的热点,不对称催化方法是获取单一异构手性化合物最具有前景的方法之一。本文综述了近年来用微生物和金属手性催化剂催化氢化β-酮酯的基础研究进展。

关键词： 四甲基二硅桥联茚基环戊二烯基四羰基二铁   合成   晶体结构   热重排反应   硅硅键   铁铁键   不对称合成  

摘要： ClMe2 SiSiMe2 Cl顺序与茚基锂和环戊二烯基锂作用 ,生成 (1 C9H7)Me2 SiSiMe2 C5H5.后者进一步与五羰基铁反应 ,得到硅硅桥联茚基环戊二烯基化合物 [η5,η5 (1 C9H6)Me2 SiSiMe2 C5H4]Fe2 (CO) 4 (2 ) .化合物 2在加热条件下发生重排反应 ,给出硅硅键和铁铁键复分解产物 Me2 Si(η5 1 C9H6)Fe(CO) 2 SiMe2 (η5 C5H4)Fe(CO) 2 (3 ) .利用X射线衍射法 ,测定了 2和