2-O-methylpancracine | 642-52-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: 2-O-methylpancracine
• 英文别名: (-)-montanine；montanine；(6R)-9c-methoxy-(6at)-5,6a,7,8,9,11-hexahydro-6r,11c-methano-benzo[b][1,3]dioxolo[4',5':4,5]benzo[1,2-e]azepin-8t-ol；O²-methyl-pancracine；Montanin；Coccinin；(1S,13S,15S,16S)-16-methoxy-5,7-dioxa-12-azapentacyclo[10.6.1.02,10.04,8.013,18]nonadeca-2,4(8),9,17-tetraen-15-ol
• CAS: 642-52-4
• 化学式: C₁₇H₁₉NO₄
• 分子量: 301.342
• InChiKey: MKYLOMHWHWEFCT-AJNGGQMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-O-methylpancracine 在 氢化钾 、 对甲苯磺酸甲酯 、 苯 作用下， 生成 manthine
  参考文献：
  名称：

  Structures of Montanine, Coccinine, and Manthine¹

  摘要：

  DOI：

  10.1021/jo01082a019
• 作为产物：
  描述：

  在 盐酸 、 bis(1,5-cyclooctadiene)diiridium(I) dichloride 、 碘苯二乙酸 、 四丁基氟化铵 、 氢气 、 二异丁基氢化铝 、 三氟乙酸 、 potassium hydroxide 、 肼 作用下， 以 甲醇 、 丙醇 、 正己烷 、 二氯甲烷 、 水 、 乙二醇 、 1,2-二氯乙烷 为溶剂， -20.0~160.0 ℃ 、6.08 MPa 条件下， 反应 52.58h， 生成 2-O-methylpancracine 、 (-)-coccinine
  参考文献：
  名称：

  受生物启发的Montanine型金莲花科生物碱的全合成

  摘要：

  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）。

  DOI：

  10.1002/anie.201307324

文献信息

• [EN] ORGANOCATALYSTS AND METHODS OF USE IN CHEMICAL SYNTHESIS<br/>[FR] ORGANOCATALYSEURS ET PROCEDES D'UTILISATION DE CES DERNIERS DANS LA SYNTHESE CHIMIQUE
  申请人：STC UNM

  公开号：WO2006007586A1

  公开（公告）日：2006-01-19

  The present invention pertains generally to compositions comprising organocatalysts that facilitate stereo-selective reactions and the method of their synthesis and use. Particularly, the invention relates to metal-free organocatalysts for facilitation of stereo-­selective reactions, and the method of their synthesis and use. These compounds have the structure of the Formulas (I) and (II). Where X is independently selected from CH2, N-Ra, O, S or C=O; Y is CH2, N-Ra, O, S or C=O, with the proviso that at least one of X or Y is CH2, and preferably both of X and Y are CH2; Ra is H, an optionally substituted C1-C12 alkyl, preferably an optionally substituted C1-C6 alkyl including a C3-C6 cyclic alkyl group, or an optionally substituted aryl group, preferably an optionally substituted phenyl group; Rb is H, an optionally substituted C1-C12 alkyl, preferably an optionally substituted C1-C6 acyclic or a a C3-C6 cyclic alkyl group, CHO, N(Me)O, CO(S)Ra or the group of Formula (III). Where Rc and Rd are each independently H, F, C1, an optionally substituted C1-C20 alkyl, preferably an optionally substituted C1-C12 alkyl, more preferably a C1-C6 alkyl, and an optionally substituted aryl group, or together Rc and Rd form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; R1 is OH, OR, NR'R', NHC(=O)R, NHSO2R; R2 is H, F, C1, an optionally substituted C1-C20 alkyl, preferably an optionally substituted C1­C6 alkyl, an optionally substituted aryl group or a =O group (which establishes a carbonyl group with the carbon to which =O is attached; R3 is H, OH, F, C1, Br, I, Cl, an optionally substituted C1-C20 alkyl, alkenyl or alkynyl ('hydrocarbyl') group, preferably an optionally substituted C1-C6 alkyl, or an optionally substituted aryl, such that the carbon to which R3 is attached has an R or S configuration; R is H, an optionally substituted C1-C20 alkyl, preferably an optionally substituted C1-C6 alkyl, or an optionally substituted aryl group, R' and R' are each independently H, an optionally substituted C1-C20 alkyl group, preferably an optionally substituted C1-C6 alkyl, or an optionally substituted aryl group; or together R' and R' form an optionally substituted heterocyclic, preferably a 4 to 7 membered optionally substituted heterocyclic group or an optionally substituted heteroaryl ring with the nitrogen to which R' and R' are attached; and wherein said compound is free from a metal catalyst.

  本发明涉及一般包括有机催化剂的组合物，该催化剂促进立体选择性反应以及其合成和使用方法。特别地，本发明涉及无金属有机催化剂以促进立体选择性反应，以及其合成和使用方法。这些化合物具有以下结构的式（I）和（II）。其中X独立地选择自CH2、N-Ra、O、S或C=O；Y为CH2、N-Ra、O、S或C=O，但至少X或Y中的一个为CH2，最好是X和Y都为CH2；Ra为H、可选择地取代的C1-C12烷基，最好是可选择地取代的C1-C6烷基，包括C3-C6环烷基，或可选择地取代的芳基，最好是可选择地取代的苯基；Rb为H、可选择地取代的C1-C12烷基，最好是可选择地取代的C1-C6无环或C3-C6环烷基，CHO、N(Me)O、CO(S)Ra或式（III）的基团。其中Rc和Rd各自独立地为H、F、C1、可选择地取代的C1-C20烷基，最好是可选择地取代的C1-C12烷基，更好地是C1-C6烷基，以及可选择地取代的芳基，或者Rc和Rd一起形成可选择地取代的碳环或可选择地取代的杂环；R1为OH、OR、NR'R'、NHC(=O)R、NHSO2R；R2为H、F、C1、可选择地取代的C1-C20烷基，最好是可选择地取代的C1-C6烷基，可选择地取代的芳基或=O基团（与=O连接的碳形成羰基基团）；R3为H、OH、F、C1、Br、I、Cl、可选择地取代的C1-C20烷基、烯基或炔基（'烃基'），最好是可选择地取代的C1-C6烷基，或可选择地取代的芳基，使得R3连接的碳具有R或S构型；R为H、可选择地取代的C1-C20烷基，最好是可选择地取代的C1-C6烷基，或可选择地取代的芳基，R'和R'各自独立地为H、可选择地取代的C1-C20烷基，最好是可选择地取代的C1-C6烷基，或可选择地取代的芳基；或者R'和R'一起形成可选择地取代的杂环，最好是4到7成员的可选择地取代的杂环基团或与R'和R'连接的氮原子形成可选择地取代的杂芳基环；其中所述化合物不含金属催化剂。
• Derivatives of montanine-type alkaloids and their implication for the treatment of Alzheimer's disease: Synthesis, biological activity and in silico study
  作者：Negar Maafi、Filip Pidaný、Jana Maříková、Jan Korábečný、Daniela Hulcová、Tomáš Kučera、Monika Schmidt、Latifah Al Shammari、Marcel Špulák、Maria Carmen Catapano、Marko Mecava、Lukáš Prchal、Jiří Kuneš、Jiří Janoušek、Eliška Kohelová、Jaroslav Jenčo、Lucie Nováková、Lucie Cahlíková

  DOI：10.1016/j.bmcl.2021.128374

  日期：2021.11

  new therapeutics is urgently needed. Thus, in the current study, twenty-eight new derivatives of montanine-type Amaryllidaceae alkaloids were synthesized and evaluated for their ability to inhibit human recombinant acetylcholinesterase (hAChE) and butyrylcholinesterase (hBuChE). Three derivatives (1n, 1o, and 1p) with different substitution patterns demonstrated significant selective inhibitory potency

  阿尔茨海默病 (AD) 是最常见的神经退行性疾病，其特征是神经元丢失和认知障碍。目前，可用于AD治疗的药物很少，迫切需要寻找新的治疗方法。因此，在目前的研究中，合成了 28 种褐煤型石蒜科生物碱的新衍生物，并评估了它们抑制人重组乙酰胆碱酯酶 ( h AChE) 和丁酰胆碱酯酶 ( h BuChE) 的能力。具有不同取代模式的三种衍生物（1n、1o和1p）对h AChE（IC 50  < 5 µM）和一种类似物1v表现出显着的选择性抑制效力, 显示出选择性h BuChE 抑制活性 (IC 50  = 1.73 ± 0.05 µM)。正如 BBB 评分所揭示的，对 CNS 可用性的预测表明，本次调查中的活性化合物应该能够通过血脑屏障 (BBB)。对两种最显着的胆碱酯酶抑制剂1n和1v进行了细胞毒性筛选和对接研究。
• Organocatalysts and Methods of Use in Chemical Synthesis
  申请人：Wang Wie

  公开号：US20070244328A1

  公开（公告）日：2007-10-18

  The present invention pertains generally to compositions comprising organocatalysts that facilitate stereo-selective reactions and the method of their synthesis and use. Particularly, the invention relates to metal-free organocatalysts for facilitation of stereo-selective reactions, and the method of their synthesis and use. These compounds have the structure of the Formulas (I) and (II). Where X is independently selected from CH 2 , N—R a , O, S or C═O; Y is CH 2 , N—R a , O, S or C═O, with the proviso that at least one of X or Y is CH 2 , and preferably both of X and Y are CH 2 ; R a is H, an optionally substituted C 1 -C 12 alkyl, preferably an optionally substituted C 1 -C 6 alkyl including a C 3 -C 6 cyclic alkyl group, or an optionally substituted aryl group, preferably an optionally substituted phenyl group; R b is H, an optionally substituted C 1 -C 12 alkyl, preferably an optionally substituted C 1 -C 6 acyclic or a a C 3 -C 6 cyclic alkyl group, CIIO, N(Me)O, CO(S)R a or the group of Formula (III). Where R c and R d are each independently H, F, Cl, an optionally substituted C 1 -C 20 alkyl, preferably an optionally substituted C 1 -C 12 alkyl, more preferably a C 1 -C 6 alkyl, and an optionally substituted aryl group, or together R c and R d form an optionally substituted carbocyclic or optionally substituted heterocyclic ring; R 1 is OH, OR, NR′R″, NHC(═O)R, NHSO 2 R; R 2 is H, F, Cl, an optionally substituted C 1 -C 20 alkyl, preferably an optionally substituted C 1 C 6 alkyl, an optionally substituted aryl group or a ═O group (which establishes a carbonyl group with the carbon to which ═O is attached; R 3 is H, OH, F, Cl, Br, I, Cl, an optionally substituted C 1 -C 20 alkyl, alkenyl or alkynyl (“hydrocarbyl”) group, preferably an optionally substituted C 1 -C 6 alkyl, or an optionally substituted aryl, such that the carbon to which R 3 is attached has an R or S configuration; R is II, an optionally substituted C 1 -C 20 alkyl, preferably an optionally substituted C 1 -C 6 alkyl, or an optionally substituted aryl group, R′ and R″ are each independently H, an optionally substituted C 1 -C 20 alkyl group, preferably an optionally substituted C 1 -C 6 alkyl, or an optionally substituted aryl group; or together R′ and R″ form an optionally substituted heterocyclic, preferably a 4 to 7 membered optionally substituted heterocyclic group or an optionally substituted heteroaryl ring with the nitrogen to which R′ and R″ are attached; and wherein said compound is free from a metal catalyst.

  本发明涉及一种包含有机催化剂的组合物，该组合物促进立体选择性反应及其合成和使用的方法。特别地，本发明涉及无金属有机催化剂，以促进立体选择性反应，以及其合成和使用的方法。这些化合物具有公式（I）和（II）的结构。其中，X独立地选自CH2、N—Ra、O、S或C═O；Y为CH2、N—Ra、O、S或C═O，但至少X或Y中的一个为CH2，最好是X和Y都为CH2；Ra为H、可选取代的C1-C12烷基，最好是可选取代的C1-C6烷基，包括C3-C6环烷基，或可选取代的芳基，最好是可选取代的苯基；Rb为H、可选取代的C1-C12烷基，最好是可选取代的C1-C6非环烷基或C3-C6环烷基，CIIO、N(Me)O、CO(S)Ra或公式（III）的基团。其中，Rc和Rd各自独立地为H、F、Cl、可选取代的C1-C20烷基，最好是可选取代的C1-C12烷基，更好是C1-C6烷基，以及可选取代的芳基，或者Rc和Rd一起形成可选取代的碳环或可选取代的杂环；R1为OH、OR、NR′R″、NHC(═O)R、NHSO2R；R2为H、F、Cl、可选取代的C1-C20烷基，最好是可选取代的C1-C6烷基、可选取代的芳基或═O基团（与═O相连的碳原子上形成羰基基团）；R3为H、OH、F、Cl、Br、I、Cl、可选取代的C1-C20烷基、烯基或炔基（“烃基”）团，最好是可选取代的C1-C6烷基，或可选取代的芳基，使得R3连接的碳原子具有R或S构型；R为II、可选取代的C1-C20烷基，最好是可选取代的C1-C6烷基，或可选取代的芳基团，R′和R″各自独立地为H、可选取代的C1-C20烷基团，最好是可选取代的C1-C6烷基，或可选取代的芳基团；或者R′和R″一起形成可选取代的杂环，最好是4到7个成员的可选取代的杂环基团或与R′和R″连接的氮原子一起形成可选取代的杂环芳基环；其中所述化合物不含金属催化剂。
• Antiproliferative activity and apoptosis-inducing mechanism of Amaryllidaceae alkaloid montanine on A549 and MOLT-4 human cancer cells
  作者：Darja Koutova、Negar Maafi、Darina Muthna、Karel Kralovec、Jana Kroustkova、Filip Pidany、Abdul Aziz Timbilla、Eva Cermakova、Lucie Cahlikova、Martina Rezacova、Radim Havelek

  DOI：10.1016/j.biopha.2023.115295

  日期：2023.10

  10 μM to explore their cytotoxic activities against a panel of eight cancer cell lines and one non-cancer cell line. Among montanine and its analogues, montanine and its derivatives 12 and 14 showed the highest cytostatic activity in the initial single-dose screening. However, the native montanine exhibited the greatest antiproliferative activity against cancer cells, with a lower mean IC50 value of

  石蒜科中发现的异喹啉生物碱因其可用于开发新药的特性而引起人们的关注。山宁对癌细胞发挥抑制作用的可能分子机制尚未有记录。在本研究中，以 10 μM 的单次测试剂量筛选了山楂碱、曼山碱和一系列源自母体生物碱山楂碱的 15 种半合成山楂碱类似物，以探索它们对一组八种癌细胞系和一种非癌症细胞系的细胞毒性活性。细胞系。在montanine及其类似物中，montanine及其衍生物12和14在最初的单剂量筛选中显示出最高的细胞抑制活性。然而，天然山煤碱对癌细胞表现出最大的抗增殖活性，平均IC 50值较低，为1.39 µM，而12的平均IC 50值为2.08 µM ， 14的平均IC 50 值为3.57 µM 。Montanine对 Jurkat 和 A549 细胞系表现出最有效的抗增殖活性，IC 50值分别为 1.04 µM 和 1.09 µM。我们还评估了山地宁的细胞毒性和细胞死亡机制。我们的结果表明，山楂碱通过
• METHOD FOR EXTRACTING THE ALKALOID FRACTION OF RHODOPHIALA BIFIDA (HERB.) TRAUB AND USES THEREOF
  申请人：Universidade Federal Do Rio Grande Do Sul-UFRGS

  公开号：EP2975041A1

  公开（公告）日：2016-01-20

  The present invention describes a method for completely extracting the alkaloid fraction (montanine) of Rhodophiala bifida (Herb.) Traub from bulbs of Rhodophiala bifida. The present invention further describes a method for treating inflammation using pharmaceutical compositions containing the alkaloid fraction of Rhodophiala bifida as the active ingredient. The present invention therefore comprises an extraction method that is faster than other extraction methods described in the literature for the alkaloid fraction of Rhodophiala bifida, dispensing with numerous changes of solvent in order to strain the plant, and the use thereof as an anti-inflammatory. The present invention is further characterised by the development of an anti-inflammatory medicinal drug for treating and preventing diseases involving inflammation and/or the local increase in the number of fibroblasts as its etiopathogenesis, such as: rheumatoid arthritis, ulcerative colitis, sepsis, acute pulmonary disease, inflammatory infections, in particular inflammatory and fibrosing diseases related to the lungs and kidneys, osteoporosis, Castleman disease, psoriatic arthritis, juvenile chronic arthritis and other non-specific inflammatory joint diseases.

  本发明描述了一种从Rhodophiala bifida (Herb.) Traub的鳞茎中完全提取Rhodophiala bifida (Herb.) Traub的生物碱部分（蒙脱宁）的方法。本发明进一步描述了一种使用含有双叶红景天生物碱部分作为活性成分的药物组合物治疗炎症的方法。因此，本发明包括一种提取方法，该方法比文献中描述的其他提取方法更快地提取红景天生物碱部分，无需多次更换溶剂以对植物进行过滤，并将其用作消炎药。本发明的进一步特点是开发了一种抗炎药物，用于治疗和预防涉及炎症和/或局部成纤维细胞数量增加作为病因的疾病，如：类风湿性关节炎、溃疡性结肠炎、败血症、急性肺部疾病、炎症感染，特别是与肺和肾有关的炎症和纤维化疾病、骨质疏松症、卡斯特曼病、银屑病关节炎、幼年慢性关节炎和其他非特异性炎症性关节疾病。