N-boc-2(R)-methylpiperidine-6(S)-carboxaldehyde | 274263-04-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N-boc-2(R)-methylpiperidine-6(S)-carboxaldehyde
• 英文别名: tert-butyl (2S,6R)-2-formyl-6-methylpiperidine-1-carboxylate；(2S,6R)-tert-butyl 2-formyl-6-methyl-1-piperidinecarboxylate
• CAS: 274263-04-6
• 化学式: C₁₂H₂₁NO₃
• 分子量: 227.304
• InChiKey: MEPVKWLQCNICCR-ZJUUUORDSA-N

物化性质

• 沸点：
  305.1±35.0 °C(Predicted)
• 密度：
  1.075±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-boc-2(R)-methylpiperidine-6(S)-carboxaldehyde 在 disodium hydrogenphosphate 、 正丁基锂 、 jones reagent 、 sodium amalgam 、 sodium cyanoborohydride 、 三氟乙酸 作用下， 以 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 丙酮 、 乙腈 为溶剂， 反应 8.0h， 生成 (3S,3aR,4R,4aS,8aR,9aS)-decahydro-4-[2-(E)-[(2S,6R)-1,6-dimethylpiperidin-2-yl]ethenyl]-3-methylnaphtho[2,3-c]furan-1(3H)-one
  参考文献：
  名称：

  Synthesis and muscarinic M2 subtype antagonistic activity of unnatural ent-himbacine and an enantiomeric pair of (2′S,6′R)-Diepihimbacine

  摘要：

  The title three compounds ent-1, 6, and ent-6 were synthesized by coupling the chiral sulfone 4 or ent-4 with the chiral piperidinaldehyde 5 or ent-5, which were readily prepared following the synthetic routes previously established by the novel total synthesis of natural himbacine 1. Their muscarinic M-2 subtype binding affinity was evaluated in comparison to that of 1, disclosing that the stereochemistry of both the tricyclic moiety and the piperidine part of 1 plays crucial roles in its potent activity. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00566-8
• 作为产物：
  描述：

  L-哌啶-2-甲酸 在 四丙基高钌酸铵 、 四甲基乙二胺 、 dimethyl sulfide borane 、 四丁基氟化铵 、 仲丁基锂 、 N-甲基吗啉氧化物 作用下， 生成 N-boc-2(R)-methylpiperidine-6(S)-carboxaldehyde
  参考文献：
  名称：

  一锅动力学动力学拆分/分子内狄尔斯-阿尔德反应的脂肪酶催化萘[2,3 - c ]呋喃-1（3 H）-one衍生物的不对称合成：（-）-himbacine的总合成

  摘要：

  很少研究使用通过醇的酶动力学动力学拆分而安装的酰基部分的一锅顺序反应。在这项工作中，通过脂肪酶/氧钒组合催化的外消旋二烯醇[4-（cyclohex-1-en-1-yl）but-3-en-2-ol或1-（ （Z）-3-（苯磺酰基）丙烯酸酯与环己基1-en-1-基）丁-2-烯-1-醇]通过一锅法进行分子内Diels-Alder反应以产生光学活性萘并[2,3 - c ]呋喃-1（3 H）-一衍生物（98％ee）。该方法已成功应用于（-）-半胱氨酸的不对称全合成。

  DOI：

  10.1016/j.bmc.2017.08.019

文献信息

• Synthesis of enantiomerically pure fire ant venom alkaloids: Solenopsins and isosolenopsins A, B and C
  作者：H. M. T. Bandara Herath、N. P. Dhammika Nanayakkara

  DOI：10.1002/jhet.5570450112

  日期：2008.1

  Concise and efficient methods for the synthesis of enantiomers of fire ant venom alkaloids solenopsin and isosolenopsin A, B, and C are described. These syntheses are based on diastereoselective electrophilic substitution of enatiomerically-pure α-lithiated 2-alkylpiperidine.

  描述了一种简单有效的合成火蚁毒生物碱slenoppsin和isosolenopsin A，B和C对映异构体的方法。这些合成基于对映体纯的α-锂化的2-烷基哌啶的非对映选择性亲电取代。
• Synthetic studies of himbacine, a potent antagonist of the muscarinic M2 subtype receptor 1. Stereoselective total synthesis and antagonistic activity of enantiomeric pairs of himbacine and (2′S,6′R)-diepihimbacine, 4-epihimbacine, and novel himbacine congeners
  作者：Masanori Takadoi、Tadashi Katoh、Akihiro Ishiwata、Shiro Terashima

  DOI：10.1016/s0040-4020(02)01358-3

  日期：2002.12

  Total synthesis of an enantiomeric pair of himbacine 1 and ent-1 was achieved in a highly stereoselective manner by employing an intermolecular Diels–Alder reaction of tetrahydroisobenzofuran 8 with chiral furan-2(5H)-one (S)-9 and (R)-9, respectively, as a key step. An enantiomeric pair of (2′S,6′R)-diepihimbacine 24 and ent-24, 4-epihimbacine 4-epi-1, and novel himbacine congeners bearing the same

  的对映体对的喜巴辛的全合成1和ENT - 1通过采用的四氢异分子间Diels-Alder反应以高立体选择性的方式实现8与手性呋喃-2（5 ħ） -酮（小号- ）9和（ř）-9作为关键步骤。的对映体对（2'小号，6' - [R）-diepihimbacine 24和ENT - 24，4- epihimbacine 4-外延- 1，和新颖的喜巴辛同源轴承相同三环部分为的1也成功通过利用键合成中间体，用于制备1，建立所述探索合成路线的收敛性和灵活性。所有使用的合成化合物均经过毒蕈碱M 2亚型受体结合亲和力测定，揭示了1的结构-活性关系的新方面。
• Cyclic amine bace-1 inhibitors having a benzamide substituent
  申请人：Cumming N. Jared

  公开号：US20050119227A1

  公开（公告）日：2005-06-02

  Disclosed are compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is R is —C(O)—N(R 27 )(R 28 ) or and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease. Also disclosed are pharmaceutical compositions and methods of treating cognitive or neurodegenerative diseases comprising the compounds of formula I in combination with a β-secretase inhibitor other than those of formula I, an HMG-CoA reductase inhibitor, a gamma-secretase inhibitor, a non-steroidal anti-inflammatory agent, an N-methyl-D-aspartate receptor antagonist, a cholinesterase inhibitor or an anti-amyloid antibody.

  本发明涉及下列式的化合物，或其药学上可接受的盐或溶剂化物： 其中， R1是 R是—C（O）—N（R27）（R28）或 其余变量如规范中所定义。本发明还涉及包含式I化合物的制药组合物。本发明还涉及治疗认知或神经退行性疾病（如阿尔茨海默病）的方法。本发明还涉及包括式I化合物与β-分泌酶抑制剂（不属于式I的），HMG-CoA还原酶抑制剂，γ-分泌酶抑制剂，非甾体抗炎药，N-甲基-D-天冬氨酸受体拮抗剂，胆碱酯酶抑制剂或抗淀粉样蛋白抗体的组合物的制药组合物和治疗认知或神经退行性疾病的方法。
• Solenopsin a, b and analogs and as novel angiogenesis inhibitors
  申请人：Bowen Phillip J.

  公开号：US20050038071A1

  公开（公告）日：2005-02-17

  The present invention relates to solenopsin A and its analogs for use as angiogenesis inhibitors. The present compounds unexpectedly exhibit good activity as angiogenesis inhibitors, which find use as antitumor/anticancer agents as well as to treat a number of conditions or disease states in which angiogenesis is a factor.

  本发明涉及用于作为血管生成抑制剂的溶蚁毒素A及其类似物。本化合物意外地表现出良好的作为血管生成抑制剂的活性，可用作抗肿瘤/抗癌剂以及治疗许多与血管生成有关的疾病状态。
• Hydronaphtho[2,3-c]furan derivatives and process for the preparation thereof
  申请人：Sagami Chemical Reasearch Center

  公开号：US06392059B1

  公开（公告）日：2002-05-21

  Intermediates for the preparation of himbacine exhibiting muscarinic M2 receptor antagonism, which are hydronaphtho[2,3-c]furan derivatives represented by general formula (1) or intermediates for the preparation thereof: wherein R1 is lower alkyl or aralky; R2 is hydrogen, lower alkyl or aralkyl; R3 and R4 together represent oxygen or methylene, or alternatively R4 is hydroxyl, lower alkoxy, aralkyloxy or lower acyloxy, with R3 being hydrogen; R5 and R6 together represent oxygen, or alternatively R6 is hydroxyl, lower alkxy, aralkyloxy or lower acyloxy, with R5 being hydrogen; and either of the broken lines is a single bond and the other thereof is a double bond, or alternatively both are single bonds.

  制备具有肌动蛋白M2受体拮抗作用的Himbacine的中间体，其为一般式（1）所代表的氢萘并[2,3-c]呋喃衍生物或其制备的中间体：其中R1为低碳基或芳基烷基；R2为氢、低碳基或芳基烷基；R3和R4一起代表氧或亚甲基，或者R4为羟基、低烷氧基、芳基氧基或低酰氧基，R3为氢；R5和R6一起代表氧，或者R6为羟基、低烷氧基、芳基氧基或低酰氧基，R5为氢；其中任意一个虚线表示单键，另一个表示双键，或者两个都是单键。