1,1-dimethyl<(2R,6S)-2-formyl-6-methyl-1-piperidine>carboxylate | 168610-13-7

• 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: 1,1-dimethyl<(2R,6S)-2-formyl-6-methyl-1-piperidine>carboxylate
• 英文别名: (2R,6S)-tert-butyl 2-formyl-6-methylpiperidine-1-carboxylate；(2R,6S)-trans-2-formyl-6-methyl-N-Boc-piperidine；(2R,6S)-tert-butyl 2-formyl-6-methyl-1-piperidinecarboxylate；trans-N-Boc-2-Methyl-6-Piperidinecarboxaldehyde；tert-butyl (2R,6S)-2-formyl-6-methylpiperidine-1-carboxylate
• CAS: 168610-13-7
• 化学式: C₁₂H₂₁NO₃
• 分子量: 227.304
• InChiKey: MEPVKWLQCNICCR-VHSXEESVSA-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：

  1,1-dimethyl<(2R,6S)-2-formyl-6-methyl-1-piperidine>carboxylate 在 disodium hydrogenphosphate 、 正丁基锂 、 jones reagent 、 sodium amalgam 、 三氟乙酸 作用下， 以 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 丙酮 为溶剂， 反应 7.5h， 生成 himbeline
  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：

  (R)-2-哌啶甲醇 在 咪唑 、 sodium hydroxide 、 四丙基高钌酸铵 、 四甲基乙二胺 、 4 A molecular sieve 、 四丁基氟化铵 、 仲丁基锂 、 N-甲基吗啉氧化物 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 1,1-dimethyl<(2R,6S)-2-formyl-6-methyl-1-piperidine>carboxylate
  参考文献：
  名称：

  Applications of Organosulfur Chemistry to Organic Synthesis:  Total Synthesis of (+)-Himbeline and (+)-Himbacine

  摘要：

  Total syntheses of(+)-himbacine (1) and (+)-himbeline (2) are described. The synthesis involves the preparation of sulfone 38 and aldehyde 42 as single enantiomers followed by coupling of these compounds using a Julia-Lythgoe olefination. The preparation of sulfone 38 features an acid-promoted intramolecular Diels-Alder reaction of an alpha,beta-unsaturated thioester while the synthesis of 42 features a Beak, alkylation of piperidine 39.

  DOI：

  10.1021/jo970612a

文献信息

• Decahydronaphtho[2,3-c]furan derivatives
  申请人：Takadoi Masanori

  公开号：US20050124658A1

  公开（公告）日：2005-06-09

  The invention provides useful novel analogues of himbacine, being an alkaloid with potent and selective antagonism against muscarine M 2 receptor. Hydronaphtho [2,3-c] furan derivatives represented by a following general formula (1) and their acid addition salts.

  该发明提供了对甲胆碱M2受体具有强效和选择性拮抗作用的有用的新型希姆巴辛类似物。由下列一般式（1）代表的羟基萘并[2,3-c]呋喃衍生物及其酸盐。
• Synthetic studies on himbacine, a potent antagonist of the muscarinic M 2 subtype receptor. Part 2: Synthesis and muscarinic M 2 subtype antagonistic activity of the novel himbacine congeners modified at the C-3 position of lactone moiety
  作者：Masanori Takadoi、Kentaro Yamaguchi、Shiro Terashima

  DOI：10.1016/s0968-0896(02)00665-x

  日期：2003.4

  ent-4-epi-2), 11-methylhimbacine 3, and 3-epihimbacine 4 in optically pure forms by employing our methodology. All of the synthesized congeners correspond to the compounds modified at the C-3 position of gamma-lactone moiety involved in 1. Among these congeners, 3-demethylhimbacine (3-norhimbacine) 2 was found to exhibit more potent muscarinic M(2) receptor binding affinity than natural 1.

  为了揭示我们先前探索的合成途径对天然hebacine 1的收敛性和灵活性，并且，为了阐明1的构效关系的一些新颖方面，我们制备了各种结构类型的新型hebacine同源物3-demethylhimbacine （3-去甲烟碱）2和4-epi-3-demethylhimbacine（（4-epi-3-norhimbacine）4-epi-2及其对映异构体（ent-2和ent-4-epi-2），11-methylhimbacine 3，和采用我们方法学的光学纯形式的3-ephimbacine 4。所有合成的同类物均对应于参与1的γ-内酯部分的C-3位置处修饰的化合物。在这些同类物中，发现3-demethylhimbacine（3-norhimbacine）2显示出更有效的毒蕈碱M（2）受体结合亲和力比天然1。
• 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。
• A novel total synthesis of (+)-himbacine, a potent antagonist of the muscarinic receptor of M2 subtype
  作者：Masanori Takadoi、Tadashi Katoh、Akihiro Ishiwata、Shiro Terashima

  DOI：10.1016/s0040-4039(99)00473-6

  日期：1999.4

  The title total synthesis was achieved by a method featuring highly stereoselective intermolecular Diels-Alder reaction of the tetrahydroisobenzofuran5 with the chiral butenolide6 as the key step. The cycloadduct4 was converted to the title alkaloid by way of the known sulfone2 in 17 steps.

  通过以四氢异苯并呋喃5与手性丁烯内酯6为关键步骤的高度立体选择性分子间狄尔斯-阿尔德反应为特征的方法，实现了标题的总合成。通过已知的砜2，以17个步骤将环加合物4转化为标题生物碱。
• Total Synthesis of (+)-Himbacine and (+)-Himbeline
  作者：Samuel Chackalamannil、Robert J. Davies、Yuguang Wang、Theodros Asberom、Darío Doller、Jesse Wong、Daria Leone、Andrew T. McPhail

  DOI：10.1021/jo981983+

  日期：1999.3.1

  isolated from the bark of Australian magnolias, is a promising lead in Alzheimer's disease research due to its potent muscarinic receptor antagonist property. We have described here a highly efficient synthetic strategy that resulted in the total synthesis of himbacine (1) in about 10% overall yield and isohimbacine (1a), an unnatural isomer of himbacine, in 18% overall yield. The total synthesis of himbacine

  Himbacine（1）是一种从澳大利亚木兰树皮中分离出来的复杂哌啶生物碱，由于其强大的毒蕈碱受体拮抗剂特性，在阿尔茨海默氏病研究中是有希望的领先者。我们在这里描述了一种高效的合成策略，该合成策略可完成总合成量约10％的hibacine（1）和总收率18％的异辛巴因（1a）（一种非天然的hebacine异构体）。最初，以分子内Diels-Alder反应为关键步骤，以生成中间体5的方式进行喜巴碱的全合成，然后与硝酮4进行[3 + 2]环加成，生成异恶唑烷衍生物3。甲基化，然后催化还原3 12'-羟基himbacine（20），脱水后得到异himbacine（1a）作为唯一产物。在另一种方法中，