(-)-brunsvigine | 1354-81-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: (-)-brunsvigine
• 英文别名: (6R)-(6at)-5,6a,7,8,9,11-hexahydro-6r,11c-methano-benzo[b][1,3]dioxolo[4',5':4,5]benzo[1,2-e]azepine-8c,9c-diol；3βH-pancracine；3βH-Pancracin；Brunsvigin；(3αO)-pancracine；brunsvigine；(1S,13S,15R,16S)-5,7-dioxa-12-azapentacyclo[10.6.1.02,10.04,8.013,18]nonadeca-2,4(8),9,17-tetraene-15,16-diol
• CAS: 1354-81-0；1071759-60-8
• 化学式: C₁₆H₁₇NO₄
• 分子量: 287.315
• InChiKey: JKZMYBLUKAMPKM-XDQVBPFNSA-N

物化性质

• 熔点：
  240°C

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  62.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (-)-brunsvigine 在 palladium on activated charcoal 氢气 作用下， 生成 6,11-dimethyl-6,11-dihydro-5H-benzo[b][1,3]dioxolo[4',5':4,5]benzo[1,2-e]azepine
  参考文献：
  名称：

  芳科的生物碱：Brunsvigine：NMR，ORD / CD和质谱，降解和相互转化研究

  摘要：

  通过NMR，CD和质谱法明确鉴定了布斯维京的5，11b-甲基吗啡啶结构。Brunsvigine的结构通过甲基化以及通过一系列Hofmann降解与其他5,11b-methanomorphanthridine生物碱相关。

  DOI：

  10.1016/0040-4020(75)87041-4
• 作为产物：
  描述：

  (2S*,3R*,4aR*,11S*,11aR*)-2,3-diacetoxy-11-(acetoxymethyl)-8,9-(methylenedioxy)-5-tosylmorphanthridine 在 4-二甲氨基吡啶 、 四氧化锇 吡啶 、 sodium periodate 、 三甲基氯硅烷 、 苯基氯化硒 、 二甲基硫 、 三氟化硼乙醚 、 sodium methylate 、 二异丁基氢化铝 、 对甲苯磺酸 、 N-甲基吗啉氧化物 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 红铝 、 sodium iodide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 氯仿 、 邻二甲苯 、 甲苯 为溶剂， 反应 34.94h， 生成 (-)-brunsvigine
  参考文献：
  名称：

  Total synthesis of montanine-type Amaryllidaceae alkaloids, which possess a 5,11-methanomorphanthridine ring system, through cyclization with sodium bis(2-methoxyethoxy)aluminum hydride (SMEAH): the first stereoselective total syntheses of (.+-.)-montanine, (.+-.)-coccinine, (.+-.)-O-acetylmontanine, (.+-.)-pancracine, and (.+-.)-brunsvigine

  摘要：

  The stereoselective total syntheses of the title alkaloids 1-5 from allylic chloride 31 are described. The key steps in the reaction sequences are as follows: (1) stereoselective hydroboration-oxidation of 12 by means of an intramolecular charge-transfer complex to afford alcohol 13 as a single isomer; (2) cyclization of tosylamide alcohol 21 with sodium bis(2-methoxyethoxy)aluminum hydride (SMEAH) to afford functionalized 5,11-methanomorphanthridine 22, which possesses the basic skeleton of montanine-type alkaloids; and (3) conversion of 30a to allylic chloride 31 by treatment with PhSeCl in MeOH under ultrasonication followed by NaIO4 oxidation. A formal total synthesis of (+/-)-manthine (6) was also accomplished.

  DOI：

  10.1021/jo00052a051

文献信息

• An Expedient Route to Montanine-Type Amaryllidaceae Alkaloids: Total Syntheses of (−)-Brunsvigine and (−)-Manthine
  作者：An-Wei Hong、Tsung-Hui Cheng、Vellingiri Raghukumar、Chin-Kang Sha

  DOI：10.1021/jo801089y

  日期：2008.10.3

  Grignard addition of 8 to 9 and detosylation afforded amine derivative 19. Pictet-Spengler cyclization of 19 with Eschenmoser's salt and subsequent hydrolysis gave enantiomerically pure (-)-brunsvigine (1). For the total synthesis of (-)-manthine (2), the key intermediate 7 was hydrolyzed to diol 21. Conversion of 21 into 22 followed by regioselective cleavage with DIBAL furnished alcohol 25. Alcohol 25 was

  （-）-brunsvigine（1）和（-）-manthine（2）的第一个总合成分别以10和18个步骤完成。通过五个步骤将（-）-亚硫酸转化为烯酮12。对烯酮12进行碘化，然后进行立体选择性还原，得到α-碘代烯丙基醇16。将醇16转化为Weinreb酰胺11，然后进行阴离子环化，得到双环烯酮10。对烯酮10进行立体选择性还原并随后进行保护，得到新戊酸酯9。格氏加成8至9和脱甲苯磺酰化得到胺衍生物19。用埃森莫瑟盐将Pictet-Spengler 19进行Pictet-Spengler环化，随后水解得到对映体纯的（-）-brunsvigine（1）。为了全合成（-）-甘氨酸（2），将关键中间体7水解为二醇21。
• Synthesis of Aza Bicyclic Enones via Anionic Cyclization:  Application to the Total Synthesis of (−)-Brunsvigine
  作者：Chin-Kang Sha、An-Wei Hong、Chien-Ming Huang

  DOI：10.1021/ol016022n

  日期：2001.7.1

  [reaction: see text] A general approach to the synthesis of aza bicyclic enones was developed via a simple two-step annulation involving a Mitsunobu protocol and anionic cyclization. According to this strategy the total synthesis of (-)-brunsvigine was accomplished with 12% overall yield.

  [反应：见正文]通过涉及Mitsunobu规程和阴离子环化的简单两步成环法开发了一种合成氮杂双环烯酮的通用方法。根据该策略，（-）-小豆子碱的总合成以12％的总产率完成。
• Bioinspired Total Synthesis of Montanine-Type<i>Amaryllidaceae</i>Alkaloids
  作者：Xu Bao、Ye-Xing Cao、Wen-Dao Chu、Hu Qu、Ji-Yuan Du、Xian-He Zhao、Xiao-Yan Ma、Cheng-Tao Wang、Chun-An Fan

  DOI：10.1002/anie.201307324

  日期：2013.12.23

  proposed biogenesis of the montanine‐type alkaloids enabled the concise asymmetric synthesis of these compounds in a divergent fashion on the basis of an unprecedented tandem oxidative dearomatization/intramolecular aza‐Michael addition as the key step. This bioinspired approach revealed a chemical connection between the cherylline‐ and montanine‐type alkaloids (see scheme).

  寻找一条共同的道路：一种受拟议的褐煤型生物碱生物合成启发的合成策略，使得在空前的串联氧化脱芳香化作用/分子内氮杂-迈克尔加成反应为关键步骤的基础上，以多样化的方式进行这些化合物的简明不对称合成。 。这种受生物启发的方法揭示了叶绿素和褐煤型生物碱之间的化学联系（参见方案）。
• Total synthesis of montanine-type Amaryllidaceae alkaloids, which possess a 5,11-methanomorphanthridine ring system, through cyclization with sodium bis(2-methoxyethoxy)aluminum hydride (SMEAH): the first stereoselective total syntheses of (.+-.)-montanine, (.+-.)-coccinine, (.+-.)-O-acetylmontanine, (.+-.)-pancracine, and (.+-.)-brunsvigine
  作者：Miyuki Ishizaki、Osamu Hoshino、Yoichi Iitaka

  DOI：10.1021/jo00052a051

  日期：1992.12

  The stereoselective total syntheses of the title alkaloids 1-5 from allylic chloride 31 are described. The key steps in the reaction sequences are as follows: (1) stereoselective hydroboration-oxidation of 12 by means of an intramolecular charge-transfer complex to afford alcohol 13 as a single isomer; (2) cyclization of tosylamide alcohol 21 with sodium bis(2-methoxyethoxy)aluminum hydride (SMEAH) to afford functionalized 5,11-methanomorphanthridine 22, which possesses the basic skeleton of montanine-type alkaloids; and (3) conversion of 30a to allylic chloride 31 by treatment with PhSeCl in MeOH under ultrasonication followed by NaIO4 oxidation. A formal total synthesis of (+/-)-manthine (6) was also accomplished.
• Alkaloids of the amaryllidaceae: Brunsvigine
  作者：R.C. Clark、F.L. Warren、K.G.R. Pachler

  DOI：10.1016/0040-4020(75)87041-4

  日期：1975.1

  The 5,11b-methanomorphanthridine structure of brunsvigine is unambiguously identified through NMR, CD and mass spectrometry. The structure of brunsvigine is related to the other 5,11b-methanomorphanthridine alkaloids by methylation as well as through a series of Hofmann degradations.

  通过NMR，CD和质谱法明确鉴定了布斯维京的5，11b-甲基吗啡啶结构。Brunsvigine的结构通过甲基化以及通过一系列Hofmann降解与其他5,11b-methanomorphanthridine生物碱相关。