(+)-Strychnine | 163956-38-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 马钱子生物碱
• 英文名称: (+)-Strychnine
• 英文别名: ent-strychnine；(4aS,5aR,8aS,13aR,15aR,15bS)-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinolin-14-one
• CAS: 163956-38-5
• 化学式: C₂₁H₂₂N₂O₂
• 分子量: 334.418
• InChiKey: QMGVPVSNSZLJIA-KGSDWGHESA-N

物化性质

• 沸点：
  559.9±50.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  25
• 可旋转键数：
  0
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-(2-(1-((1S,5R,7R,E)-4-(2-(tert-butoxy)ethylidene)-7-hydroxy-2-(2,2,2-trifluoroacetyl)-2-azabicyclo[3.2.1]octan-7-yl)vinyl)phenyl)-1,3-dimethyl-1,3,5-triazinan-2-one 在 盐酸 、 氢氧化钾 、 硫酸 、 sodium methylate 、 sodium acetate 、 乙酸酐 、 二异丁基氢化铝 、 溶剂黄146 、 sodium sulfate 、 锌 、 lithium diisopropyl amide 作用下， 以 甲醇 、 乙醇 、 水 、 乙腈 为溶剂， 反应 29.42h， 生成 (+)-Strychnine
  参考文献：
  名称：

  Asymmetric Total Syntheses of (-)- and (+)-Strychnine and the Wieland-Gumlich Aldehyde

  摘要：

  The first asymmetric total syntheses of (-)-strychnine, ent-strychnine, and the Wieland-Gumlich aldehyde are described with full experimental details. The total synthesis of (-)-strychnine was realized in 24 steps and 3% overall yield from (1R,4S)-(+)-4-hydroxy-2-cyclopentenyl acetate (28). This synthesis fully controls the six stereogenic centers and forms the C(20) double bond of (-)-strychnine with high diastereoselection (>20:1). In the first stage of the synthesis, the (R)-cyclopentenylstannane 8 is prepared in nine steps and 30% overall yield (40% with one recycle of 38) as summarized in Scheme 4. Palladium-catalyzed carbonylative coupling of 8 with the 2-iodoaniline derivative 7 provides enone 6, which is converted to the 2-azabicyclo[3.2.1]octane 5 in seven additional steps. This latter sequence proceeds in 36% overall yield (Scheme 6). The central step of the total synthesis is aza-Cope-Mannich rearrangement of 5 which proceeds in 98% yield to form the pentacyclic intermediate 4 (Scheme 7). In five additional steps 4 is converted to the Wieland-Gumlich aldehyde 2, which is the ultimate precursor of (-)strychnine. A slight modification of this synthesis strategy allowed ent-strychnine to be prepared and provided the first samples of this unnatural enantiomer for pharmacological studies (Scheme 8). The efficiency and conciseness of this synthesis provide an important benchmark of the power of the aza-Cope rearrangement-Mannich reaction to solve formidable problems in alkaloid construction.

  DOI：

  10.1021/ja00126a017

文献信息

• Enantioselective Total Synthesis of Wieland-Gumlich Aldehyde and (−)-Strychnine
  作者：Daniel Solé、Josep Bonjoch、Silvina García-Rubio、Emma Peidró、Joan Bosch

  DOI：10.1002/(sici)1521-3765(20000218)6:4<655::aid-chem655>3.0.co;2-6

  日期：2000.2.18

  A total synthesis of (-)-strychnine in 15 steps from 1,3-cyclohexanedione in 0.15% overall yield is described. The sequence followed in the assembling of rings is: E-->AE [2-(2-nitrophenyl)-1,3-cyclohexanedione]-->ACE (3a-aryloctahydroindol-4-one)-->ACDE (arylazatricyclic core)-->ABCDE (strychnan skeleton)-->ABCDEF (Wieland-Gumlich aldehyde)-->ABCDEFG (strychnine). The key steps of the synthesis are

  描述了由1,3-环己二酮以0.15％的总收率分15步合成（-）-士的宁。组装环后的顺序是：E-> AE [2-（2-硝基苯基）-1,3-环己二酮]-> ACE（3a-芳基氢化吲哚-4-酮）-> ACDE（芳基三环核心） ）-> ABCDE（Strychnan骨架）-> ABCDEF（Wieland-Gumlich醛）-> ABCDEFG（Strychnine）。合成的关键步骤是3a-（2-硝基苯基）-八氢吲哚-4-酮环系统的对映选择性结构，以及通过还原性Heck环化反应生成关键中间体（-）-14闭合哌啶环。相反，路易斯酸促进的α-烷氧基炔丙基硅烷-烯酮环化没有导致合成上有用的氮杂三环ACDE中间体。
• Asymmetric Total Synthesis of (+)-Strychnine
  作者：Liping He、Xiaobei Wang、Xiaoqing Wu、Zhaoxiang Meng、Xin Peng、Xiao-Yu Liu、Yong Qin

  DOI：10.1021/acs.orglett.8b03686

  日期：2019.1.4

  A synthetic strategy for the catalytic asymmetric total synthesis of (+)-strychnine is disclosed. Key features of this synthesis include an organocatalytic enantioselective Michael addition to establish the chirality of the starting building block, a photoinduced radical cascade reaction to access the Corynanthe alkaloid intermediate, and a bioinspired cascade rearrangement to generate the core of

  公开了用于（+）-金丝氨酸的催化不对称全合成的合成策略。该合成的关键特征包括建立起始手性的手性的有机催化对映选择性迈克尔加成反应，光诱导的自由基级联反应以进入Corynanthe生物碱中间体，以及受生物启发的级联重排以生成Strychnos生物碱的核心。
• Asymmetric Total Syntheses of (-)- and (+)-Strychnine and the Wieland-Gumlich Aldehyde
  作者：Steven D. Knight、Larry E. Overman、Garry Pairaudeau

  DOI：10.1021/ja00126a017

  日期：1995.5

  The first asymmetric total syntheses of (-)-strychnine, ent-strychnine, and the Wieland-Gumlich aldehyde are described with full experimental details. The total synthesis of (-)-strychnine was realized in 24 steps and 3% overall yield from (1R,4S)-(+)-4-hydroxy-2-cyclopentenyl acetate (28). This synthesis fully controls the six stereogenic centers and forms the C(20) double bond of (-)-strychnine with high diastereoselection (>20:1). In the first stage of the synthesis, the (R)-cyclopentenylstannane 8 is prepared in nine steps and 30% overall yield (40% with one recycle of 38) as summarized in Scheme 4. Palladium-catalyzed carbonylative coupling of 8 with the 2-iodoaniline derivative 7 provides enone 6, which is converted to the 2-azabicyclo[3.2.1]octane 5 in seven additional steps. This latter sequence proceeds in 36% overall yield (Scheme 6). The central step of the total synthesis is aza-Cope-Mannich rearrangement of 5 which proceeds in 98% yield to form the pentacyclic intermediate 4 (Scheme 7). In five additional steps 4 is converted to the Wieland-Gumlich aldehyde 2, which is the ultimate precursor of (-)strychnine. A slight modification of this synthesis strategy allowed ent-strychnine to be prepared and provided the first samples of this unnatural enantiomer for pharmacological studies (Scheme 8). The efficiency and conciseness of this synthesis provide an important benchmark of the power of the aza-Cope rearrangement-Mannich reaction to solve formidable problems in alkaloid construction.