(+)-macroline | 2269-93-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 大灵碱生物碱
• 英文名称: (+)-macroline
• 英文别名: (+)-Macrolin；Macroline；3-[(1S,12S,13R,14R)-13-(hydroxymethyl)-3,16-dimethyl-3,16-diazatetracyclo[10.3.1.02,10.04,9]hexadeca-2(10),4,6,8-tetraen-14-yl]but-3-en-2-one
• CAS: 2269-93-4
• 化学式: C₂₁H₂₆N₂O₂
• 分子量: 338.45
• InChiKey: UFYREEIANXVLMJ-RKOGWWSCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  45.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  pleiocarpamine 、 (+)-macroline 在 盐酸 作用下， 反应 24.0h， 以41%的产率得到villalstonine
  参考文献：
  名称：

  Enantiospecific Synthesis of (-)-Alstonerine and (+)-Macroline as Well as a Partial Synthesis of (+)-Villalstonine

  摘要：

  The enantiospecific synthesis of (-)-alstonerine (5) and (+)-macroline (8), as well as a partial synthesis of the Alstonia bisindole alkaloid villalstonine (2) has been completed. In addition, a more stable macroline equivalent 9 was prepared. The stereochemistry at C(15) and C(16) in 5 and 8 has been successfully installed by a stereoselective Claisen rearrangement followed by stereospecific hydroboration-oxidation of the exocyclic methylene function at C-16. The E ring in alstonerine 5 was constructed by a regioselective cyclization followed by a novel Swern oxidation under modified conditions [(COCl)(2)/DMSO/CH2Cl2, -78 degrees C to -10 degrees C/1.5 h; Et(3)N], whereas the C(20)-C(21) enone system in macroline (8) was generated via a convenient one pot process from the beta-diol 45. Condensation of either synthetic (+)-macroline (8) or the macroline equivalent 9 with natural pleiocarpamine 7 in 0.2 N HCl furnished the antiamoebic, antimalarial bisindole alkaloid villalstonine 2. This constitutes the first partial synthesis of any of the Alstonia bisindoles from a synthetically derived indole moiety.

  DOI：

  10.1021/ja00099a021
• 作为产物：
  描述：

  (6S,10S)-(-)-5,12-dimethyl-9-oxo-6,7,8,9,10,11-hexahydro-6,10-imino-5H-cyclooctindole 在 吡啶 、 sodium hydroxide 、 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 重铬酸吡啶 、 9-borabicyclo[3.3.1]nonane dimer 、 四丁基氟化铵 、 双氧水 、 对甲苯磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， 生成 (+)-macroline
  参考文献：
  名称：

  合成大分子/ sarpagine生物碱的通用方法。（+）-大麦碱的总合成

  摘要：

  由四环酮5合成了（+）-甲基1和更稳定的当量2。合成中的关键步骤涉及立体选择性Claisen重排，然后对所得烯烃14进行硼氢化氧化，以在C-15和C-16处设置正确的立体化学。

  DOI：

  10.1016/0040-4039(93)88069-u

文献信息

• General approach for the synthesis of macroline/sarpagine alkaloids. The total synthesis of (+)-macroline
  作者：Yingzhi Bi、James M. Cook

  DOI：10.1016/0040-4039(93)88069-u

  日期：1993.7

  the tetracyclic ketone 5. The key steps in the synthesis involved a stereoselective Claisen rearrangement followed by hydroboration-oxidation of the resulting olefin 14 to set the correct stereochemistry at C-15 and C-16.

  由四环酮5合成了（+）-甲基1和更稳定的当量2。合成中的关键步骤涉及立体选择性Claisen重排，然后对所得烯烃14进行硼氢化氧化，以在C-15和C-16处设置正确的立体化学。
• Die absolute Konfiguration von Macrolin, einem Abbauprodukt des Alkaloides Villalstonin 179. Mitteilung über organische Naturstoffe
  作者：Gisela Neukomm、Erika Kletzhäundler、Manfred Hesse

  DOI：10.1002/hlca.19810640112

  日期：1981.2.4

  The Absolute Configuration of Macroline, a Degradation Product of the Alkaloid Villalstonine

  生物碱Villalstonine的降解产物Macroline的绝对构型
• Stereoselective Access to the Core Structure of Macroline-Type Indole Alkaloids: Total Synthesis of Macroline and Alstomicine
  作者：Vilas D. Kadam、Sridhara Shanmukha Rao B.、S. K. Mahesh、Mithun Chakraborty、S. Phani Babu Vemulapalli、Satya Narayana Dayaka、Gangarajula Sudhakar

  DOI：10.1021/acs.orglett.8b01921

  日期：2018.8.17

  Rapid synthesis of the pentacyclic core structure of macroline-type indole alkaloids, and its application in the total synthesis of macroline and alstomicine is described. The core structure was accomplished in a highly stereocontrolled manner via two key steps, Ireland–Claisen rearrangement and Pictet–Spengler cyclization, commencing from a readily available starting material l-tryptophan, which obviated

  描述了大环型吲哚生物碱的五环核结构的快速合成及其在大环线和阿司他汀的全合成中的应用。核心结构是通过两个关键步骤以高度立体控制的方式完成的：爱尔兰-克莱森重排和Pictet-Spengler环化，这是从容易获得的起始原料l-色氨酸开始的，从而消除了特定手性来源作为外部催化剂的需要，试剂或内部辅助剂。
• An Improved Total Synthesis of (+)-Macroline and Alstonerine as Well as the Formal Total Synthesis of (−)-Talcarpine and (−)-Anhydromacrosalhine−methine
  作者：Xuebin Liao、Hao Zhou、Jianming Yu、James M. Cook

  DOI：10.1021/jo061652u

  日期：2006.11.1

  enantiospecific total synthesis of gram quantities of both (+)-macroline 3 and the macroline equivalent 4. This sequence is compared to the enolate-driven cross-coupling process. The intermediate 4 was also converted into (−)-alstonerine 1 via modification of an intramolecular Tsuji−Wacker oxidation. This sequence resulted in an improved total synthesis of (−)-talcarpine 5 and (−)-anhydromacrosalhine−methine

  描述了分子内Pd催化的α-乙烯基化过程。这种环化已被用于对映体的克量的（+）-宏氨酸3和大分子等效物4的总合成。将该序列与烯醇盐驱动的交叉偶联过程进行比较。中间体4还通过分子内Tsuji-Wacker氧化的修饰而转化为（-）-alstonerine 1。该序列还导致（-）-塔卡普林5和（-）-脱水大麦芽菜碱-次甲基6的总合成得到改善。
• A partial synthesis of the Alstonia bisindole alkaloid villalstonine
  作者：Yingzhi Bi、James M. Cook、Philip W. LeQuesne

  DOI：10.1016/s0040-4039(00)76690-1

  日期：1994.6

  The partial synthesis of villalstonine 1 has been completed by coupling the macroline equivalent 2a with plant-derived (+)-pleiocarpamine 3 in 0.2N aq. hydrochloric acid in the presence of fluoride ion.

  Villalstonine 1的部分合成已通过在0.2 N aq中将大分子当量2a与植物衍生的（+）-pleiocarpamine 3偶联而完成。盐酸中存在氟离子。