(1S,2S,6R,14R,15R,16S,20R)-18-(4-bromophenyl)-11,15-dimethoxy-5-methyl-13-oxa-5,18-diazaheptacyclo[13.5.2.12,8.01,6.02,14.016,20.012,23]tricosa-8(23),9,11,21-tetraene-17,19-dione | 766550-46-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: (1S,2S,6R,14R,15R,16S,20R)-18-(4-bromophenyl)-11,15-dimethoxy-5-methyl-13-oxa-5,18-diazaheptacyclo[13.5.2.12,8.01,6.02,14.016,20.012,23]tricosa-8(23),9,11,21-tetraene-17,19-dione
• CAS: 766550-46-3
• 化学式: C₂₉H₂₇BrN₂O₅
• 分子量: 563.448
• InChiKey: VTSMUNAOIOCODQ-WIAZSDGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.48
• 重原子数：
  37.0
• 可旋转键数：
  3.0
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  68.31
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (1S,2S,6R,14R,15R,16S,20R)-18-(4-bromophenyl)-11,15-dimethoxy-5-methyl-13-oxa-5,18-diazaheptacyclo[13.5.2.12,8.01,6.02,14.016,20.012,23]tricosa-8(23),9,11,21-tetraene-17,19-dione 在 bis-triphenylphosphine-palladium(II) chloride 、 N-碘代丁二酰亚胺 、 copper(l) iodide 、 三乙胺 、 三苯基膦 、 三氟乙酸 作用下， 以 苯 为溶剂， 反应 2.0h， 生成 1-(2-trimethylsilylethynyl)-7α,8α-[N-(4-bromophenyl)-2,5-dioxopyrrolidino][3,4-h]-6,14-endo-etheno-6,7,8,14-tetrahydrothebaine
  参考文献：
  名称：

  Synthetic transformations of isoquinoline alkaloids. Synthesis of N′-substituted 1-alkynyl-7α,8α-(2,5-dioxopyrrolidino)-[3,4-h]-6,14-endo-ethenotetrahydrothebaines and their transformations

  摘要：

  The iodination of N'-substituted (2,5-dioxopyrrolidino)[3,4-h]-6,14-endo-ethenotetrahydrothebaines with N-iodosuccinimide in trifluoroacetic acid afforded depending on the excess of the reagent either 1-iodo- or 1,2-diiodoendo-ethenotetrahydrothebaines. The Sonogashira reaction of 1-iodo-6,14-endo-ethenotetrahydrothebaines with trimethylsilylacetylene led to the formation of N'-substituted 1-(trimethylsilylethynyl)-(2,5-dioxopyrrolidino)-[3,4-h]-6,14-endo-ethenotetrahydrothebaines whose desilylation cleanly furnished the corresponding 1-ethynylendo-ethenotetrahydrothebaines. The Mannich reaction of the acetylene derivatives of tetrahydrothebaine with amines and formaldehyde catalyzed by compounds of Cu(I) provided 1-[3-(morpholin-4-yl)propynyl]-, 1-[3-(4-methylpiperazin-1-yl)propynyl]-, and 1-[3-(4-tert-butoxycarbonylpiperazin-1-yl)propynyl]-(2,5-dioxopyrrolidino)[3,4-h]-6,14-endo-ethenotetrahydrothebaines.

  DOI：

  10.1134/s1070428012110103
• 作为产物：
  描述：

  蒂巴因 、 N-(4-溴苯基)马来酰亚胺 以 乙醇 为溶剂， 以91%的产率得到(1S,2S,6R,14R,15R,16S,20R)-18-(4-bromophenyl)-11,15-dimethoxy-5-methyl-13-oxa-5,18-diazaheptacyclo[13.5.2.12,8.01,6.02,14.016,20.012,23]tricosa-8(23),9,11,21-tetraene-17,19-dione
  参考文献：
  名称：

  Thebaine Adducts with Maleimides. Synthesis and Transformations

  摘要：

  霹雳-阿尔德反应中，神仙草碱与马来酰亚胺反应具有结构特异性，生成含有N′-烷基、环烷基、芳基或者芳香烷基取代基的[7,8,3′,4′]-琥珀酰亚胺-内-乙烯四氢神仙草碱。在S-巴醇与(7α,8α)-无水-内-乙烯四氢神仙草碱反应中，形成了N′-[1(S)-羟甲基-2-甲基丙基]-琥珀酰亚胺-6,14-内-乙烯四氢神仙草碱。利用LiAlH4还原加成物得到N′-取代的7,8-吡咯烷基-内-乙烯四氢神仙草碱。用NaBH4还原融合琥珀酰亚胺得到了相应的2′α-羟基内酰胺衍生物。用BBr3对四氢神仙草碱吡咯烷衍生物进行O-去甲基化，得到四氢奥利帕韦系列化合物。四氢神仙草碱有关的琥珀酰亚胺衍生物的O-去甲基化生成对应的6-去甲基-内-乙烯四氢奥利帕韦。对N′-(4-羟基苯乙基)取代的四氢神仙草碱琥珀酰亚胺衍生物进行了烷基化条件的研究。

  DOI：

  10.1007/s11178-005-0306-8

文献信息

• Synthetic transformations of isoquinoline alkaloids. Synthesis of 1-halo derivatives of endo-ethenotetrahydrothebaine and their behavior in the heck reaction
  作者：V. T. Bauman、E. E. Shul’ts、M. M. Shakirov、G. A. Tolstikov

  DOI：10.1134/s1070428007040070

  日期：2007.4

  Bromination of endo-ethenotetrahydrothebaine derivatives having a pyrrolidine ring fused at the C-7-C-8 stop bond, namely 1'-substituted 4,5 alpha-epoxy-6 alpha,14-etheno-3,6-dimethoxy-17-methyl-2',5',7 beta,8 beta-tetrahydro-1'H-14 alpha-pyrrolo[3',4':7,8]morphinan-2',5'-diones, 1'-aryl-4,5 alpha-epoxy-6 alpha,14-etheno-3,6-dimethoxy-17-methyl-2',5',7 beta,8 beta-tetrahydro-1'H-14 alpha-pyrrolo[3',4':7,8]morphinans, and 4,5 alpha-epoxy-6 alpha,14-etheno-2'+/--hydroxy-3,6- dimethoxy-17-methyl-1'-phenyl-2',5',7 beta,8 beta-tetrahydro-1'H-14 alpha-pyrrolo[3',4':7,8]morpphinan-5'-one, with molecular bromine in formic acid smoothly afforded the corresponding 1-bromo derivatives. Iodination of 4,5 alpha-epoxy-6 alpha,14-etheno-3,6-dimethoxy-17-methyl-1'-phenyl-2',5',7 beta,8 beta-tetrahydro-1'H-14 alpha-pyrrolo[3',4':7,8]-4,5 alpha-epoxy-6 alpha,14-etheno-3,6-dimethoxy-17-methyl-1'-phenyl-2',5',7 beta,8 beta-tetrahydro-1'H-14 alpha-pyrrolo[3',4':7,8]-morphinan-2',5'-dione with iodine(I) chloride gave 4,5 alpha-epoxy-6 alpha,14-etheno-1-iodo-3,6-dimethoxy-17-methyl-1'-phenyl-2',5',7 beta,8 beta-tetrahydro-1'H-14 alpha-pyrrolo[3',4':7,8]morphinan-2',5'-dione. The resulting 1-halo derivatives were brought into the Heck reaction with acrylic acid esters to obtain 1-[(E)-2-(alkoxycarbonyl)ethenyl]-substituted compounds. Demethylation of the 6-methoxy group in 1-bromo-endo-ethenotetrahydrothebaines was accomplished using boron(III) bromide in chloroform.