4-碘-2-甲氧基-6-三甲基硅烷基-3-吡啶甲醛 | 174092-75-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 4-碘-2-甲氧基-6-三甲基硅烷基-3-吡啶甲醛
• 英文名称: 4-iodo-2-methoxy-6-trimethylsilanyl-3-pyridinecarboxaldehyde
• 英文别名: 4-iodo-2-methoxy-6-trimethylsilylpyridine-3-carbaldehyde；4-iodo-2-methoxy-6-trimethylsilyl-3-pyridine-carboxaldehyde；3-formyl-4-iodo-2-methoxy-6-trimethylsilylpyridine；4-Iodo-2-methoxy-6-trimethylsilanyl-pyridine-3-carbaldehyde
• CAS: 174092-75-2
• 化学式: C₁₀H₁₄INO₂Si
• 分子量: 335.217
• InChiKey: NQKIFRSZGVLWSK-UHFFFAOYSA-N

物化性质

• 沸点：
  318.3±42.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.05
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-碘-2-甲氧基-6-三甲基硅烷基-3-吡啶甲醛 在 palladium diacetate 三乙基硅烷 、 四氧化锇 、 hydroquinindine-2,5-diphenyl-4,6-pyrimidinediyl diether 、 四丁基溴化铵 、 氢碘酸 、 碘 、 六甲基二锡 、 一氯化碘 、 sodium hydride 、 potassium carbonate 、 calcium carbonate 、 lithium bromide 作用下， 以 乙二醇二甲醚 、 N,N-二甲基甲酰胺 、 三氟乙酸 、 苯 为溶剂， 生成 喜树碱
  参考文献：
  名称：

  Curran, Dennis P.; Ko, Sung-Bo; Josien, Hubert, Angewandte Chemie, 1995, vol. 107, # 23/24, p. 2948 - 2950

  摘要：

  DOI：
• 作为产物：
  描述：

  2-溴-6-甲氧基吡啶 在 正丁基锂 、 叔丁基锂 作用下， 生成 4-碘-2-甲氧基-6-三甲基硅烷基-3-吡啶甲醛
  参考文献：
  名称：

  通过氟混合物合成法制备 560 种单一纯 Mappicine 类似物的化合物库

  摘要：

  溶液相混合物合成具有效率优势和有利的反应动力学。然而，由于使用传统的分离和鉴定过程难以获得单独的、纯的最终产品，这种技术的应用受到了阻碍。这里介绍的是一种解决分离和识别问题的混合物合成新策略。一系列有机底物的成员与一系列不同链长的氟标签配对。然后将标记的起始材料混合并通过多步反应过程。氟色谱法用于根据标签的氟含量对带标签的产品混合物进行分层，以提供混合物的各个纯组分，这些组分被分离以释放最终产品。含氟混合物合成的效用通过天然产物 mappicine 的 560 元类似物库的制备得到证明。七组分混合物通过四步混合物合成（两个一锅法和两个平行步骤）进行，以将两个额外的多样性点合并到四环核心上。建立了中间体的分析和纯化方法，以控制混合物合成的质量。

  DOI：

  10.1021/ja026947d

文献信息

• Intermediates in the synthesis of camptothecin and related compounds and synthesis thereof
  申请人：University of Pittsburgh

  公开号：US06252079B1

  公开（公告）日：2001-06-26

  The present invention provides a short, convergent total synthesis of irinotecan and derivative compounds which comprises of a novel 4+1 radical annulation wherein the precursor is reacted with an aryl isonitrile having the formula wherein X is Br or I, and R4 is an alkyl group, an allyl group, a propargyl group or a benzyl group, and R16 is H, a C1-C6 alkoxy group, a group wherein p is an integer between 4 and 12, or a C1-C12 acyclic dialkylamino group. The present invention also provides novel chemical intermediates for such 4+1 radical annulations.

  本发明提供了伊立替康及其衍生化合物的短、收敛的全合成方法，包括一种新颖的4+1自由基环合反应，其中前体物质与具有以下结构的芳基异腈发生反应：其中X为Br或I，R4为烷基、烯丙基、丙炔基或苄基，R16为H、C1-C6烷氧基、p为4至12之间的整数的羟基，或C1-C12非环二烷基氨基基团。本发明还提供了用于这种4+1自由基环合反应的新型化学中间体。
• Catalytic Enantioselective Synthesis of (20S)-Camptothecin Intermediates Using Cyanosilylation of Ketones Promoted by D-Glucose-derived Lanthanide Catalyst
  作者：Masakatsu Shibasaki、Kazuo Yabu、Shuji Masumoto、Motomu Kanai、Wu Du、Dennis P. Curran

  DOI：10.3987/com-02-s49

  日期：——

  An efficient catalytic enantioselective synthetic route was developed for Curran's versatile camptothecin intermediate (5). The key step is the catalytic enantioselective cyanosilylation of ketone (7) using a chiral samarium (Sm) complex. The target ketone cyanohydrin (6) was obtained with 90% ee using 2 mol % of the catalyst. A gadolinium (Gd) complex derived from the same chiral ligand could also

  为 Curran 的多功能喜树碱中间体 (5) 开发了一种有效的催化对映选择性合成路线。关键步骤是使用手性钐 (Sm) 配合物对酮 (7) 进行催化对映选择性氰基化。使用 2 mol% 的催化剂获得目标酮合氰化氢 (6)，ee 为 90%。源自相同手性配体的钆 (Gd) 配合物也可用作对映选择性催化剂以合成 Corey 的中间体 (11)。
• Intermediates and methods of preparation of intermediates in the enantiomeric synthesis of (20R)homocamptothecins and the enantiomeric synthesis of (20R)homocamptothecins
  申请人：——

  公开号：US20030073840A1

  公开（公告）日：2003-04-17

  A method of synthesizing a compound having the formula: 1 from a compound having the formula: 2 wherein R 1 is hydrogen, fluorine, chlorine or SiR 5 R 6 R 7 , wherein R 5 , R 6 , and R 7 are independently the same or different an alkyl group or an aryl group, R 2 is an alkyl group, R 3 is a protecting group, R 4 is an alkyl group, an allyl group, a propargyl group —CO 2 H, or a benzyl group, R 8 is —CO 2 R 10 , wherein R 10 is an alkyl group or an aryl group, X 1 is OH and X 2 is H, includes the step of exposing compound (III) to at least one of an organic acid or an inorganic acid. A compound has the general formula (III).

  一种合成具有公式1的化合物的方法：从具有公式2的化合物开始，其中R1是氢、氟、氯或SiR5R6R7，其中R5、R6和R7分别是相同或不同的烷基或芳基，R2是烷基，R3是保护基，R4是烷基、烯丙基、丙炔基-CO2H或苄基，R8是-CO2R10，其中R10是烷基或芳基，X1是OH，X2是H，包括将化合物（III）暴露于有机酸或无机酸之一的步骤。化合物具有通用公式（III）。
• A General Synthetic Approach to the (20S)-Camptothecin Family of Antitumor Agents by a Regiocontrolled Cascade Radical Cyclization of Aryl Isonitriles
  作者：Hubert Josien、Sung-Bo Ko、David Bom、Dennis P. Curran

  DOI：10.1002/(sici)1521-3765(199801)4:1<67::aid-chem67>3.0.co;2-f

  日期：1998.1

  A general and efficient synthesis of (20S)-camptothecin (1a) is reported. A key common intermediate containing the pyridone and lactone (DE) rings of camptothecin and most derivatives was constructed from 2-trimethylsilyl-6-methoxypyridine by a series of metalation reactions and a Heck cyclization to provide an achiral bicyclic enol ether. Sharpless asymmetric dihydroxylation followed by lactol oxidation and iododesilylation produced the key intermediate in 94% enantiomeric excess. Alkylation with propargyl bromide and a cascade radical reaction with phenyl isonitrile then produced 1a. About 20 other penta- and hexacyclic analogues of camptothecin with differing single or multiple substituents at C7, C9, C10, C11, and/or C12 were made by changing the propargylating agent and the isonitrile. Included among these are several drug candidates and the approved drugs topotecan and irinotecan. The synthesis of the prodrug irinotecan is direct one that does not pass through the active metabolite. The use of ortho-trimethylsilyl-substituted isonitriles allows the regioselective synthesis of camptothecin analogues in cases where isomeric mixtures are formed from the parent isonitriles. The synthesis of the derivatives relies on the broad scope and functional group tolerance of the key cascade radical reaction.
• Asymmetric total synthesis of (20R)-homocamptothecin, substituted homocamptothecins and homosilatecans
  作者：Ana E Gabarda、Wu Du、Thomas Isarno、Raghuram S Tangirala、Dennis P Curran

  DOI：10.1016/s0040-4020(02)00632-4

  日期：2002.8

  An efficient asymmetric synthesis of a key DE lactone pyridone intermediate in the synthesis of homocamptothecin is reported. The synthesis is scalable and features a Stille coupling and a Sharpless asymmetric epoxidation as the key steps. The key intermediate has been parleyed into homocamptothecin and an assortment of fluorinated homocamptothecins and homosilatecans (7-silylhomocamptothecins), thereby providing the first asymmetric entry to this important new class of antitumor agents. (C) 2002 Published by Elsevier Science Ltd.