基于三氟甲基砌块的催化不对称傅-克反应研究进展

引入三氟甲基基团可以显著提高有机分子的化学和代谢稳定性、亲脂性以及在细胞膜中的渗透性,因此发展高效合成三氟甲基化合物,特别是手性三氟甲基化合物的方法具有非常重要的意义.基于三氟甲基砌块的催化不对称傅-克反应可以高效高选择性获得手性三氟甲基芳香化合物,是最近发展起来的一个研究热点.自从日本Mikami小组采用手性钛络合物研究了首例基于三氟甲基砌块的催化不对称傅-克反应,不同种类的手性有机金属催化剂(如手性钛,铜,锌,锆,钯,镱,钇,镍,钙等金属络合物)和手性有机小分子催化剂(如金鸡纳碱,手性脯氨醇硅醚,手性磷酸等)都在这类不对称催化反应中得到应用.作者主要对反应组分(特别是不同类型的三氟甲基砌块)、反应条件、反应机理和合成应用等方面的研究进行了综述.最后,对这类反应所存在的问题和局限性进行了总结,并对今后发展方向作了展望.     

不对称催化合成中手性膦配体的研究进展(Ⅰ)(待续)

对近十多年来不对称催化合成领域中出现的手性膦配体进行了综述,按其不对称中心以及结构上的特征加以分类,并对其催化性能进行总结。     

不对称催化合成中手性膦配体的研究进展(Ⅱ)(续完)

对近十多年来不对称催化合成领域中出现的手性膦配体进行了综述,按其不对称中心以及结构上的特征加以分类,并对其催化性能进行总结     

5-羟基色胺受体激动剂(1R,2S)-(-)-2-(2-羟基苯基)-N,N-二丙基环丙胺的不对称合成

利用手性双唑啉与三氟甲磺酸亚铜催化2-甲氧基苯乙烯与重氮乙酸二环己基甲酯的不对称环丙烷化反应合成了手性环丙烷羧酸酯,用氢氧化钠对其进行选择性水解得到全反式环丙烷羧酸,其ee值经GC测定为88%.进一步经过Curtius重排、烷基化等反应及重结晶等步骤合成了光学纯的具有生理活性的环丙胺化合物1a和1b.     

1-苯基-3-甲基-5-芳氧基-1H-吡唑-4-甲醛-O-[(2-氯吡啶-5-基)甲基]肟的合成与生物活性

利用1-苯基-3-甲基-5-芳氧基吡唑4-甲醛肟与2-氯-5-氯甲基吡啶发生缩合反应,合成了14个新型含吡啶环的吡唑肟醚衍生物.通过1H NMR,13C NMR和元素分析对所合成的化合物进行了结构表征.初步生物活性测试结果表明,在试验浓度下部分化合物具有一定的杀菌和植物生长调节活性.     

新型2-[4-(3-吗啉基丙氧基)苯氧基]乙基异硫脲的合成

以对苄氧基苯酚为原料,经三步反应合成了2-[4-(3-氯丙氧基)苯氧基]乙醇(3);在3中引入吗啉基团制得2-[4-(3-吗啉丙氧基)苯氧基]乙醇(4);利用甲磺酰氯将4的羟基转化为离去基团,再引入硫脲基团成功地合成了新型含硫脲基的酚醚类衍生物——2-[4-(3-吗啉丙氧基)苯氧基]乙基异硫脲,其结构经1H NMR,13C NMR和MS表征。     

2-[二-(2-氯乙基)-胺基]-5-苄氧基-1,3,2-氧氮磷杂环己烷-2-氧化物的不对称合成

2-[二-(2-氯乙基)-胺基]-5-苄氧基-1,3,2-氧氮磷杂环己烷-2-氧化物是抗癌药物Endoxan的衍生物,其光学异构体的合成已有报道.本文报道了我们从廉价易得的手性原料天然-L-酒石酸开始,通过较为简捷的合成路线,完成了对目标化合物全部4个光学异构体的合成.化合物的有关数据参见表1.     

α-[4-(N,N-二甲基)苯基]-α-三氟甲基-α-炔丙胺的不对称合成

以N,N-二甲基对溴苯胺为起始原料,利用含氟砌块法,经3步反应合成了α-[4-(N,N-二甲基)苯基]-α-三氟甲基-α-炔丙胺,其结构经1H NMR,13C NMR,19F NMR,IR,MS和HR-MS确证。     

铑催化不对称氢化2-苯基-2-丙烯醇合成手性2-苯基丙醇

通过铑催化不对称催化氢化的方法,实现了2-苯基-2-丙烯醇的不对称催化氢化,对一系列单齿及双齿磷配体进行了筛选,在温和的条件下,以较高对映体选择性的合成了手性2-苯基丙醇,最高获得了70%的ee值。     

Synthesis and bioactivity of novel (3-chloro-5-(trifluoromethyl)pyridin-2-yloxy)phenyl containing acrylate and acrylonitrile derivatives

Fifteen novel (3-chloro-5-(trifluoromethyl)pyridin-2-yloxy)phenyl containing Baylis-Hillman adduct derivatives were designed and synthesized. Evaluation of their biological activities showed that methyl 2-((3-(3-chloro-5-(trifluoromethyl)pyridin-2-yloxy)phenoxy)(phenyl)methyl)acrylate (2g) exhibited efficient broad-spectrum fungicidal activity, with 100% control of wheat powdery mildew and cucumber downy mildew and 98% control of cucumber anthracnose at 400 g ai/ha. Some of the other title compounds 2, 3 and two Baylis-Hillman bromide intermediates (11a, 11b) had moderate to good fungicidal activity.     

3-氯-5-(三氟甲基)-2-乙胺基吡啶的合成

以2,3-二氯-5-三氟甲基吡啶为起始原料,经亲核取代、脱羧、加氢还原及酰胺水解等4步反应合成了3-氯-5-(三氟甲基)-2-乙胺基吡啶,纯度97.4%,总收率61.36%,其结构经1H NMR确证。     

1-芳基-3-(3-(4-氧香豆素基)苯基)硫脲衍生物的合成及抑菌活性

为了筛选出具有较高抑菌活性的含香豆素的硫脲类衍生物,本文以4-羟基香豆素为原料,经氯化、醚化、异硫氰酸化和加成反应合成了一系列1-芳基-3-(3-(4-氧香豆素基)苯基)硫脲衍生物,其结构经红外光谱(IR)、核磁共振谱(NMR)和质谱(MS)等技术手段进行了表征。结果表明,目标化合物对水稻白叶枯菌和柑橘溃疡菌均具有较好的抑制活性。其中化合物4k、4l、4m和4n抑制水稻白叶枯菌活性EC_(50)值分别为137.42、131.05、129.23和117.43 mg/L,优于对照药剂噻菌铜的活性(195.24 mg/L);化合物4k、4l、4m和4n抑制柑橘溃疡菌活性EC_(50)值分别为97.02、94.31、102.28和90.52 mg/L,优于噻菌铜的活性(120.25 mg/L)。     

Asymmetric Synthesis of (3R, 5R)-3-((tert-Butyldimethylsily)oxy)-5-((Z)-2-Bromovinyl)-Tetrahydro-Furan-2-one, an Intermediate for the Synthesis of Fostriecin

Fostriecin(CI-920) 11 a potential anticancer agent presently in phase I clinical trials at NCI is a novel phosphate ester produced by Streptomyces pulveraceus. Scheme 1 1 2 3 5 4 Synthesis of C10 epimer of compound 1 had been reported by Just G2. during the determination of its structure. On the basis of Just’s synthesis, a revised retro-asymmetric synthetic route of Fostriecin (scheme 1) was designed here of which compound 3 was synthesized from 5 with C3 in R configuration correspondi…     

Synthesis and Crystal Structure of （Z）-Methyl-3-methoxy-2-{2-[（4-（E-3-p-tolylacryloyl）phenoxy）methyl]phenyl}acrylate

The title compound,(Z)-methyl-3-methoxy-2-{2-[(4-(E-3-p-tolylacryloyl)phenoxy)-methyl]phenyl}acrylate,was synthesized and determined by X-ray single-crystal diffraction. The crystal belongs to the triclinic system,space group P1 with a = 8.0157(8),b = 12.5748(13),c = 13.3768(14) ,α = 64.770(2),β = 75.720 (2),γ = 89.784(2)°,μ = 0.085 mm-1,Mr = 442.49,V = 1174.1(2) 3,Z = 2,Dc = 1.252 g/cm3,F(000) = 468,T = 294(2) K,R = 0.0603 and wR = 0.1498 for 2644 observed reflections with I 2σ(I). X-ray diffraction analysis reveals that the single crystal contains strong non-classical hydrogen bonds. The preliminary bioassay showed that the title compound exhibits inhibitory activity against the Pseudoperoniospora cubensis and Rhizoctonia solani at the test concentration of 200 mg/L.     

Synthesis,Crystal Structure and Biological Activity of 2-Chloro-5-(((5-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-4-phenyl-4H-1,2,4-triazol-3-yl)thio)methyl)thiazole

The title compound 5-chloro-2-(((5-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)-4-phenyl-4H-1,2,4-triazol-3-yl)thio)methyl)thiazole(C17H12Cl F3N6S2) was synthesized, and its structure was confirmed by 1H NMR, 13 C NMR, HRMS and X-ray diffraction. It crystallizes in the triclinic system, space group P1 with a = 8.214(5), b = 10.188(6), c = 12.378(7) ?, α = 81.679(8), β = 87.994(8), γ = 70.351(8)°, D_c = 1.572 g/cm~3, Z = 2, V = 965.2(9) ?~3, the final R = 0.0591 and w R = 0.1113 for 3005 observed reflections with I 2σ(I). The preliminary biological test shows that the title compound possesses good herbicidal activities(80%) against rape at 200 μg/mL.     

Synthesis,Crystal Structure and Anti-breast Cancer Activity of ((3S,5R)-5-((1H-1,2,4-triazol-1-yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methyl 4-Methylbenzenesulfonate

The new heterocycle compound ((3S,5R)-5-((1H-1,2,4-triazol-1-yl)methyl)-5-(2,4-difluorophenyl)tetrahydrofuran-3-yl)methyl 4-methylbenzenesulfonate (1), designed using((3R,5S)-5-(2,4-difluorophenyl)-5-iodotetrahydrofuran-3-yl)methyl isobutyrate(2) as the start material, was successfully obtained via multiple synthesis route and finally characterized by IR, ~1H NMR, and single-crystal X-ray crystallography. In addition, the in vitro anticancer activities of the newly synthesized complex 1 have been emulated against three human breast cancer cell lines BT474, MCF7 and MB.     

3-(2-吡啶基)-1,2,4-三唑衍生物的合成

1,2,4-三唑是五员含氮杂环化合物,其五员环上的三个N原子均可以同金属配位,因此它与金属离子的结合力很强,配位方式也很丰富,所构筑出来的配合物在生物、医药、磁性材料、手性催化剂、电致发光材料等方面都存在着诱人的应用前景,因而成为化学界和生物界的研究热点[1-4].