关键词： REDUCTION   ENANTIOMERS   EPOXIDES  

摘要： The asymmetric synthesis of (6S,8R)-, (6S,8S)-, (6R,8S)- and (6R,8R)-heptacosane-6,8-diols from (2S)-, (2R)-1-[(R)-p-tolylsulfinyl]-2-heptanols and 1-icosanal is described.

关键词： asymmetric synthesis   Grignard reagents   oxidations  

摘要： A chiral Grignard reagent with the metal-bearing carbon atom as the sole stereogenic center has been generated by asymmetric synthesis in >90 % ee (see scheme). Such reagents allow the elucidation of the stereochemical course of subsequent reactions (such as the shown oxidation), which provides hints to the mechanism (electron transfer reactions or polar additions).

关键词： aldol reactions   antitumor agents   macrolides   natural products   total synthesis  

摘要： The total synthesis of the antitumor marine macrolide phorboxazole B (1) has been realized. The phorboxazoles are representative of a new structural class of macrolides and are among the most cytostatic natural products known: inhibiting the growth of tumor cells at nanomolar concentrations. Key fragment couplings include a highly selective double stereodifferentiating aldol reaction, a metalated-oxazole alkylation, and an oxazole-stabilized Wittig olefination. Following macrocyclization, a highly stereoselective chelation-controlled addition of a side-chain alkenyl metal species provides the full carbon framework of phorboxazole B.

关键词： CYTOCHROME-P-450  

摘要： The asymmetric synthesis of the unlabeled and [D-8]-labeled terminal precursors, 4 ((-)-(S)-dihydroxyverbacine) and 19, respectively, in the biogenesis of the spermine alkaloids aphelandrine (5) and orantine (6), respectively, is described. A partial synthesis of the alkaloid (-)-(S)-[(E)-4-methoxycinnamoyl]buchnerine (10) is also presented.

关键词： aldol reactions   antitumor agents   macrolides   natural products   total synthesis  

摘要： The total synthesis of the antitumor marine macrolide phorboxazole B (1) has been realized. The phorboxazoles are representative of a new structural class of macrolides and are maong the most cytostatic natural products known: inhibiting the growth of tumor cells at nanomolar concentrations. Key fragment couplings inlucde a highly selective double stereodiffentiating aldol reaction, a metalated-oxazole alkylation, and an oxazole-stabilized Wittig olefination. Following macrocyclization, a highly stereoseclective chelation-controlled addition of a side-chain alkenyl metal species provides the full carbon framework of phorboxazole B.

关键词： β-内酰胺  

摘要： 介绍了不对称合成 β-内酰胺的研究进展 ,详细讨论了手性 β-内酰胺的合成方法。

关键词： Chiral auxiliary   azides   based   CYCLOADDUCT   geometry   Asymmetric synthesis   Cycloaddition Reaction   Nitrones   Phenylalanine  

摘要： The diastereomerically single chiral sulfonyl substituated isoxazolidine derivative (+)-(1) under bar (1) was prepared from L-phenylalanine via practical procedures. The acrylamide (-)-(2) under bar underwent dipolar cycloaddition reaction with nitrones and an azide with a high level of diastereoselectivity. The facial selectivity observed was consistent with the geometry optimized steric energies of the cycloadducts disclosed by MM2 calculations.

关键词： Asymmetric Diels-Alder   Pantolactone, fragmentation   Pyranonaphthoquinones  

摘要： The enantioselective synthesis of a cyclopentannulated analogue 8 of the pyranonaphthoquinone antibiotic kalafungin 1 is described. Addition of cyclopentadiene to naphthoquinone 2 which bears a pantalactone chiral auxiliary at C-2, afforded cyclopentannulated naphthofuran 4 after tin(IV) chloride induced fragmentation of the initial Diels-Alder adduct 3. The pantolactone auxiliary was then removed using lithium borohydride and the resultant aldehyde 5 converted to a methyl ketone 6 by treatment with methyl lithium followed by oxidation with manganese dioxide. The enantiomeric excess of methyl ketone 6 obtained in this manner was established to be 96% by chiral HPLC. Oxidative rearrangement of methyl ketone 6 using silver(II) oxide and nitric acid afforded lactol 7 which was reduced to cyclopentannulated pyranonaphthoquinone 8 using triethylsilane and trifluoroacetic acid.

关键词： 硫醚化合物   甲硫醚   不对称氧化   中国医学科学院中国协和医科大学   不对称合成方法   手性亚砜  

摘要： 手性催化剂作用下的硫醚类化合物的不对称催化氧化，是合成手性亚砜类化合物的简便、有效的方法。本论文以对甲基苯甲硫醚和对硝基苯甲硫醚为底物，研究并比较了20种手性配体作用下，上述硫醚类化合物不对称催化氧化反应的对映选择性，采用的手性配体有：（2R，3R）-酒石酸甲酯，（2R，3R）-酒石酸乙酯，（2R，3R）-酒石酸异丙酯，（2R，3R）-酒石酸苄酯，（2R，3R）-N，N’-二苯基酒石酰胺，（2R，3R）-N，N’-二苄基酒石酰胺，（2R，3R）-N，N’-二间甲苯基酒石酰胺，（2R，3R）-N，N’-二对甲苯基酒石酰胺，R-（+）-联萘二酚，S-（-）-联萘二酚，R-（-）-6，6′-二溴-1，1′-联荼-2，2′-二酚，S-（+）-6，6′-二溴-1，1′-联萘-2，2′-二酚，R-（+）-联萘二胺，S-（-）-联萘二胺，R-（+）-2，2′-N，N′-二（甲基氨基）-1，1′-联萘，S-（-）-2，2′-N，N′-二（甲基氨基）-1，1′-联萘，R-（+）-2，2′-二（甲磺酰氨基）-1，1′-联荼，S-（-）-2，2′-二（甲磺酰氨基）-1，1′-联萘，R-（-）-2，2′-N，N′-二（邻羟基苯亚甲基氨基）-1，1′-联萘，S-（+）-2，2′-N，N′-二（邻羟基苯亚甲基氨基）-1，1，1′-联萘。 将上述手性配体与不同的有机金属化合物、氧化剂组合成多种不对称氧化体系对硫醚进行氧化，发现Ti（O-iPr）4-（2R，3R）-酒石酸异丙酯-H2O-TBHP-分子筛（氧化体系Ⅰ），Ti（O-iPr）4-[R-（+）-联萘二酚]-H2O-TBHP（Ⅱ），Ti（O-iPr）4-[S-（-）-联萘二酚]-H2O-TBHP（Ⅲ），Ti（O-iPr）4-[R-（-）-6，6′-二溴-1，1′-联萘-2，2′-二酚]-H2O-TBHP（Ⅳ），和Ti（O-iPr）4-[S-（+）-6，6′-二溴-1，1′-联萘-2，2′-二酚]-H2O-TBHP（Ⅴ）等体系对于对甲基苯甲硫醚的不对称催化氧化均有较好的对映选择性，在这些氧化体系的作用下，产物对甲基苯甲亚砜的e.e.值最高达到77％。其中Ti（O-iPr）4-（2R，3R）-酒石酸异丙酯-H2O-TBHP-分子筛（Ⅰ）体系还可用于对硝基苯甲硫醚的不对称催化氧化，产物对硝基苯甲亚砜的e.e.值可以达到61％。 将上述优选出的催化氧化体系用于手性亚砜类药物莫达非尼和奥美拉唑的不对称催化氧化合成之中，使用Ti（O-iPr）4-[S-（+）-6，6′-二溴-1，1′-联萘-2，2′-二酚]-H2O-TBHP（Ⅴ）体系氧化莫达非尼前体硫醚化合物为莫达非尼时的收率和e.e.值分别为80％和46％，但前述几种氧化体系用于奥美拉唑的不对称催化氧化合成时未得到理想的结果，其收率和e.e.值仅为35％和9.2％。 同时，还建立了一种与现有工业生产方法相比较，更为简单、有效的合成消旋奥美拉唑的新的氧化方法，收率稳定在82％-92％之间，有希望应用于奥美拉唑的工业化生产。 通过化学合成和拆分制备了二十种光活手性配体。其中合成消旋联萘二胺的方法是新建立的，与文献方法比较收率提高，操作简便，更适合于大量制备。

关键词： alkaloids   amino acids   hydrogenation   ruthenium  

摘要： The enantioselective ruthenium promoted hydrogenation of beta-keto ester, derived from (S)- or (R)-proline and (S)-pipecolic acid, provided a new efficient route to hydroxylated pyrrolizidine or indolizidine ring systems in diastereomeric excesses up to 99%. A practical synthesis of (+)-alpha-conhydrine is also reported. (C) 2000 Wiley-Liss,Inc.