关键词： 亚胺   查尔酮   不对称加成   迈克尔加成   手性N,P二茂铁配体  

摘要： 本文以有机合成方法学为目标,合成了五个具有面手性和中心手性的含N,P配位原子的二茂铁手性配体36-40;研究了它们在铜催化下的二乙基锌对膦酰亚胺的不对称加成反应和在铜催化下的二乙基锌对查尔酮的不对称共轭加成反应中的应用。探讨了N-二茂铁亚甲基氮杂环丙烷的制备过程中的关环方法,并合成了三个新的手性N-二茂铁亚甲基氮杂环丙烷。 一、含N,P配位原子的手性二茂铁配体在铜催化下的二乙基锌对亚胺的不对称加成反应中的应用研究 从光学纯的二茂铁胺出发,合成了以下五个化合物36-40;研究了它们在铜催化二乙基锌对膦酰亚胺的不对称加成反应中的催化效率和不对称诱导效果,考察了温度、催化剂用量、以及手性配体和铜盐的比例等因素对反应的影响。最佳条件下取得了高达95%的化学产率和高达97%的ee值,高化学产率高光学收率地得到了对映体纯的两种构型的手性胺。研究表明,配体36和37的面手性和中心手性的匹配是获得高催化效果的关键,它们的非对映体40几乎不能催化反应的进行,表明它的面手性和中心手性是“错配对”的。

关键词： desymmetrization   Diels-Alder reaction   enzymes   natural products  

摘要： In their pioneering report on the diene synthesis,or the Diels-Alderreaction,Otto Diels and Kurt Alder recognized the profound impact that this pericyclic reactionwould have in the syntheses of"complex compounds related to or identtical with natural products"andspeculated that this process may also be nvolved in the biosyntheses of natural products.

关键词： alkaloids   asymmetric syntheses   Heck reactions   insecticides   ring-closing metatheses  

摘要： In 1997 researchers at Bayer AG reported on two new Amaryllidaceaealkaloids,[1] cripowellins A (1) and B (2), which had been isolated from the bulbs and roots ofCrinum powellii, a popular ornamental plant in Europe.[2], [3] The two compounds differ only intheir glycosidic parts. The assumption that both of these sugar moieties are derived biogenicallyfrom β-D-glucose accounts for the depicted absolute stereochemistry. Their common aglycon comprisesa [5.3.2]bicyclic core, a structural motif unique among the Amaryllidaceae alkaloids. One of bothbridgehead atoms is a trisubstituted amide N atom and therefore not a stereogenic center.

关键词： OPTICALLY ACTIVE LIGANDS   METAL COMPLEXES   STEREOSPECIFIC INFLUENCES   CONFORMATIONAL ANALYSIS   COBALT ATOMS   CONFIGURATION   ION   INFORMATION   ISOMERS   NMR  

摘要： A publication by Alexander P Smirnoff in Helvetica Chimica Acta in 1920 [6]describes the first synthesis of a coordination species, i.e., of tris(propane-1,2-diamine-kappaN-1,kappa N-2)platinum(4+) ([Pt-IV(pn)(3)](4+)), where it was shown that the configuration of achiral center in the ligand can influence the configuration at the metal. The present investigationof [Pt-IV(pn)(3)](4+) was carried out by NMR spectroscopy, where all nuclei in the metal complexwere used as sources of information, i.e., H-1, C-13, N-15, and Pt-195. C-13-NMR and N-15-NMRspectroscopy (of isotopically enriched complex) were especially informative for the analysis ofisomer distribution. Stereoselectivity in the formation reaction of the complexes is rather modest,whereas Delta-, and Lambda-isomers can be separated efficiently by crystallization. A mixture of[Pt{(S)-pn}(3)](4+) and [Pt{(R)-pn}(3)](4+) shows no scrambling of the enantiomeric ligands, thusproving the inertness of the complexes.

关键词： 扁桃酸   D-(-)-苯甘氨酸丁酯   R-(-)-α-环己基扁桃酸   异丁醛   拆分   不对称合成  

摘要： 在大量的不对称合成医药试剂中,手性化合物扁桃酸及其衍生物α-环己基扁桃酸都是重要的前体合成原料。光学活性的扁桃酸具有很好的生物分解性,是目前最受瞩目的酸性光学拆分剂,它可使多数外消旋体胺类和氨基酸类经非对映体异构盐形成法进行光学拆分;而且它本身又可用于一些药品中间体,如R-(-)-扁桃酸用于头孢菌类系列抗生素-羟苄四唑头孢菌素的侧链修饰剂等。目前国际市场上光学活性的扁桃酸需求约以年均10%以上的速度增长,成为热点的精细化工中间体。手性α-环己基扁桃酸不仅可以用来合成奥昔布宁和脱乙基奥昔布宁等解痉药,还可以用来合成奥芬溴铵和羟苄利明等抗胆碱药;相比较它们的消旋结构,光学活性的药物有更有效的药理作用。因此,单一对映体α-环己基扁桃酸的市场前景非常巨大。在国外,从二十世纪六十年代开始,如何开发出高效、简便的不对称合成路径一直是研究的热点。而国内的研究还未见报道。为协助常州胜杰化工有限公司开发出手性新品,打进国际市场,本论文主要研究了扁桃酸的光学拆分及其衍生物R-(-)-α-环己基扁桃酸的不对称合成。与此同时,也研究了拆分剂D-(-)-苯甘氨酸丁酯及其盐酸盐的制备方法。 扁桃酸的光学拆分主要研究了形成非对映异构体拆分的方法。通过本论文的比较及实验,选用了D-(-)-苯甘氨酸丁酯盐酸盐作为拆分剂,它与消旋扁桃酸的摩尔比为1.0～1.2,两者在10℃下溶于水溶液中,用NaOH滴定,得到好的拆分效率。通过实验知道,形成的非对映异构体盐D-苯甘氨酸丁酯.R-扁桃酸从水溶液中结晶析出,经酸化,用乙醚提取后,得到了R-(-)-扁桃酸,有98.9%的收率和32%的光学纯度。而从酸化后的母液中用乙醚提取了S-(+)-扁桃酸,有90%的收率和67%的光学纯度。另外,作者也回收套用了拆分后的母液,减少了整个拆分成本,提高了收率。 在拆分剂的制备过程中,主要用了D-(-)-苯甘氨酸和正丁醇为起始原料,氯化亚砜为酯化的催化剂。选择在低温下缓慢滴加氯化亚砜,一般在5℃左右进行滴加;滴加完毕后,在室温下反应1小时左右,直至完全生成酰氯盐酸盐。然后进行回流酯化,反应时间最佳为70分钟。为了扩大化生产的需要,可以将母液直接套用,达到节省原料,节约生产成本,提高收率的目的。最终得到了摩尔收率在85%以上,光学纯度为98.1%的产品D-苯甘氨酸丁酯盐酸盐。接着选用10%氢氧化钠溶液作为制备D-苯

关键词： AZA-WITTIG REARRANGEMENT   ALPHA-AMINO-ACIDS   -WITTIG REARRANGEMENT   ENANTIOSELECTIVE SYNTHESES   WITTIG REARRANGEMENT   AZA--WITTIG REARRANGEMENTS   PROPARGYLIC ALCOHOLS   MIGRATING TERMINUS   ENOLATE TERMINUS   DERIVATIVES  

摘要： A survey of 16 different chiral auxiliaries and a variety of strategies found that an (-)-8-phenylmenthol ester of a glycine derived migrating group can control the absolute stereochemistry of aza-[2,3]-Wittig sigmatropic rearrangements with diastereoselectivities of ca. 3 : 1 with respect to the auxiliary. In two specific examples, ca. 50% yields of enantiomerically pure products were obtained after chromatographic purification. These were synthetically manipulated with no erosion of stereochemistry into intermediates that completed formal asymmetric syntheses of (+)- HyMePro and (-)- kainic acid.

关键词： 不对称还原   4-氯乙酰乙酸乙酯   (S)-4-氯-3-羟基丁酸乙酯   木兰假丝酵母   生物催化   E coli M15(pQE30-car)  

摘要： (S)-4-氯-3-羟基丁酸乙酯(（S）-CHBE)是一种重要的手性药物中间体,可用于合成HGM-CoA还原酶抑制剂和β-1,4-二氢吡啶类钙离子通道阻断剂等药物,具有重要的应用价值。 首先,从实验室保藏的七株酵母菌株中筛选出具有较高还原能力和手性选择性的菌株——木兰假丝酵母（Candida magnoliae）。优化其还原反应条件,结果表明,25g/L木兰假丝酵母在30℃,以10g/L的葡萄糖为辅助底物的缓冲溶液（pH6.0）中能将12.1g/L的4-氯乙酰乙酸乙酯（COBE）还原为（S）-CHBE,此时产物得率为87.5%,对映体过量值（e.e.值）为76.4%。当细胞量增至45g/L时产物得率和e.e.值分别提高至99.2%和85.2%。提高底物浓度后,发现单相反应过程存在比较严重的底物及产物抑制。底物分批加入可以部分解除底物抑制,但产物抑制作用仍然存在。 为减轻产物抑制的影响,研究Candida magnoliae两相体系中不对称还原反应,并优化其还原反应条件。结果表明,在水/乙酸丁酯两相体系中,30℃时在添加50g/L葡萄糖的缓冲溶液中,100g/L的木兰假丝酵母可在滴加底物条件下将60.5g/L的COBE还原为（S）-CHBE,产物得率为93.8%,e.e.值为85.7%。 此外,还研究了经热处理的木兰假丝酵母催化COBE立体选择性还原反应。新鲜木兰假丝酵母菌株经热处理（55℃、30min）后具有高度的立体选择性,且不受还原条件的影响,产物为（S）型,e.e.值大于99%。且此过程中不需添加任何商业辅酶NADP+/NADPH及葡萄糖脱氢酶（GDH）。在水/乙酸丁酯两相体系中,经55℃加热30min处理后的Candida magnoliae（100g/L）,可将60.5g/L的COBE还原为（S）-CHBE,产物得率为58.5%,其e.e.值大于99%。 最后,构建了具有较高羰基还原酶酶活的大肠杆菌菌株*** M15（pQE30-car）和较高葡萄糖脱氢酶酶活的大肠杆菌菌株*** M15（pQE30-gdh0310）。优化其培养条件和不对称还原反应条件,30℃时50g/L的*** M15（pQE30-car）和50g/L的*** M15（pQE30-gdh0310）在100mM,pH6.0的磷酸盐缓冲液中能将12.1g/L的COBE还原为（S）-CHBE,其产物得率为78.4%,其e.e.值大于99%。在水/乙酸丁酯两相体系中,100 g/L的*** M15（pQE30-car）和100 g/L的*** M15（pQE30-gdh0310）,在pH6.0的磷酸盐缓冲液中（50g/L的葡萄糖）振荡反应（100 r/min）时,可将60.5g/L的COBE转化为（S）-CHBE,产物得率为42.0%,其e.e.值大于99%。

关键词： asymmetry   biphenyl diester   bis(oxazoline)   coupling   oxazoline  

摘要： Biphenyl lignan (beta-DDB) (2), an effective drug in the treatment of hepatitis, was for the first time asymmetrically synthesized via a chiral oxazoline mediated Ullmann coupling. The two enantiomers of beta-DDB have been obtained in this way by using the optically pure amino alcohols L-valinol and D-valinol, respectively. However, attempts to synthesize enantiopure alpha-DDB (1) by the same method failed because of the racemization of 1 at room temperature in solution.

关键词： dimethyl compounds   enolate   Asymmetric synthesis   Antibiotic  

摘要： An enantiospecific synthesis of the AB fragment of lactonamycin (5) is achieved in eight steps from dimethyl D-tartrate. Ester enolate chemistry features prominently in the sequence.

关键词： bis(cyclohept-1-ene) derivatives   ozonolysis   polyfunctional spiroketals   selective protection  

摘要： Quick access to polyfunctional spiroketal (3R)-4-[(2S,6R,8R, 10S)-4,4-bis(ethylthio)-10-hydroxy-8-(2-hydroxyethyl)- 1,7-dioxaspiro[5.5]undec-2-yl]butane- 1,3-diol [(+)-19] is now available through the stereoselective functionalization of enantiomerically pure protected tetrol (4R,4'R,6R,6'R)- 1, l'-methylenebis[4-[(benzyloxy)methoxy]-6-[(triethylsilyl)-oxy]cyclohept-1-ene [(-)-9], derived from 2,2'-methylenedifuran. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).