(1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl acetate | 200432-36-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl acetate
• 英文别名: [(1R,2S,5R)-5-methyl-2-(2-phenylpropan-2-yl)cyclohexyl] acetate
• CAS: 200432-36-6
• 化学式: C₁₈H₂₆O₂
• 分子量: 274.403
• InChiKey: FUVDQRFHOXIVOL-KBRIMQKVSA-N

物化性质

• 沸点：
  349.2±11.0 °C(Predicted)
• 密度：
  1.00±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl acetate 在 硝酸铵 、 三氟乙酸酐 作用下， 以 氯仿 为溶剂， 反应 4.5h， 以98%的产率得到(1R,2S,5R)-5-methyl-2-[1-methyl-1-(4-nitrophenyl)ethyl]cyclohexyl acetate
  参考文献：
  名称：

  Total Synthesis of (−)-Epibatidine Using an Asymmetric Diels−Alder Reaction with a Chiral N-Acylnitroso Dienophile

  摘要：

  An asymmetric total synthesis of(-)-epibatidine (1), isolated from the skin of the Ecuadorian poison frog, Epipedobates tricolor, of the family Dendrobatidae, has been achieved by virtue of the development of asymmetric hetero Diels-Alder (D-A) cycloaddition with an N-acylnitroso dienophile bearing the optically active 8-arylmenthol as a chiral source. Thus, in situ oxidation of the hydroxamic acid ent-laf incorporating the (1S,2R,5S)-8-(2-naphthyl)menthyl auxiliary was performed using the Swern conditions to produce the acylnitroso dienophile, which reacted at once with 2-chloro-5-(1,5-cyclohexadienyl)pyridine (7) to provide the (1S,4R)-meta-aza cycloadduct 24 as a major diastereoisomer. The observed facial diastereoselectivity is consistent with a transition-state model with the naphthyl group in "stacked" position and with the acylnitroso group in the s-cis conformation, wherein pi attractive interaction between the naphthyl and nitrosocarbonyl groups may contribute to facial control. Compound 24 underwent hydrogenation followed by removal of the chiral auxiliary with LiH2NBH3 and reductive cleavage of the N-O bond with Mo(CO)(6) to give the amino alcohol derivative 29, which was converted to (-)-epibatidine via bromination followed by cyclization.

  DOI：

  10.1021/jo9813078
• 作为产物：
  描述：

  长叶薄荷酮 在 吡啶 、 copper(I) bromide 、 4-二甲氨基吡啶 、 sodium 、 异丙醇 作用下， 反应 22.0h， 生成 (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenylethyl)cyclohexyl acetate
  参考文献：
  名称：

  Total Synthesis of (−)-Epibatidine Using an Asymmetric Diels−Alder Reaction with a Chiral N-Acylnitroso Dienophile

  摘要：

  An asymmetric total synthesis of(-)-epibatidine (1), isolated from the skin of the Ecuadorian poison frog, Epipedobates tricolor, of the family Dendrobatidae, has been achieved by virtue of the development of asymmetric hetero Diels-Alder (D-A) cycloaddition with an N-acylnitroso dienophile bearing the optically active 8-arylmenthol as a chiral source. Thus, in situ oxidation of the hydroxamic acid ent-laf incorporating the (1S,2R,5S)-8-(2-naphthyl)menthyl auxiliary was performed using the Swern conditions to produce the acylnitroso dienophile, which reacted at once with 2-chloro-5-(1,5-cyclohexadienyl)pyridine (7) to provide the (1S,4R)-meta-aza cycloadduct 24 as a major diastereoisomer. The observed facial diastereoselectivity is consistent with a transition-state model with the naphthyl group in "stacked" position and with the acylnitroso group in the s-cis conformation, wherein pi attractive interaction between the naphthyl and nitrosocarbonyl groups may contribute to facial control. Compound 24 underwent hydrogenation followed by removal of the chiral auxiliary with LiH2NBH3 and reductive cleavage of the N-O bond with Mo(CO)(6) to give the amino alcohol derivative 29, which was converted to (-)-epibatidine via bromination followed by cyclization.

  DOI：

  10.1021/jo9813078

文献信息

• Solvent-Controlled Diastereoselective Synthesis of Cyclopentane Derivatives by a [3 + 2] Cyclization Reaction of α,β-Disubstituted (Alkenyl)(methoxy)carbene Complexes with Methyl Ketone Lithium Enolates
  作者：José Barluenga、Jorge Alonso、Francisco J. Fañanás

  DOI：10.1021/ja029170x

  日期：2003.3.1

  11 with methyl ketone lithium enolates 2 leads to the corresponding five-membered carbocyclic compounds 4 or diast-4 and 12. The influence of the solvent and/or cosolvent (PMDTA), which turned out to be crucial to direct the reaction to 4 or diast-4, is studied, and a tentative mechanism according to these facts is proposed. In addition, the reaction of carbene complex 1a with alkynyl methyl ketone

  α,β-不饱和甲氧基卡宾配合物 1 和 11 与甲基酮烯醇锂 2 反应生成相应的五元碳环化合物 4 或 diast-4 和 12。溶剂和/或助溶剂 (PMDTA) 的影响，导致研究了将反应导向 4 或 diast-4 的关键，并提出了根据这些事实的初步机制。此外，卡宾配合物 1a 与炔基甲基酮烯醇锂的反应可以通过反应条件的轻微变化直接生成 [3 + 2] 或 [4 + 1] 的正式环化产物。最后，提出了与卡宾配合物 1a、烯醇锂 2 和醛 18 的连续三组分偶联反应，以非对映选择性的方式得到羟基羰基化合物 19 和三环聚醚 20。
• Practical Formal Total Syntheses of the Homocamptothecin Derivative and Anticancer Agent Diflomotecan via Asymmetric Acetate Aldol Additions to Pyridine Ketone Substrates
  作者：René Peters、Martin Althaus、Christian Diolez、Alain Rolland、Eric Manginot、Marc Veyrat

  DOI：10.1021/jo060928v

  日期：2006.9.1

  scalable asymmetric routes to DE ring fragment 7, a key building block in the synthesis of the homocamptothecin derivative diflomotecan 4, are described. The “acetal route” starts from 2-chloro-4-cyanopyridine 8 and represents an enantioselective and optimized modification of the original racemic discovery chemistry synthesis. The inefficient optical resolution procedure was replaced by an efficient asymmetric

  描述了两种实际，有效且可扩展的至DE环片段7的不对称路线，DE环片段7是高喜树碱衍生物双氟醚4合成中的关键组成部分。“缩醛途径”始于2-氯-4-氰基吡啶8，代表对映体选择性和对原始外消旋发现化学合成的优化修饰。低效率的光学拆分程序被高效的不对称乙酸酯醛醇加成剂（dr 87:13）取代到酮基质上，这是生成具有高立体选择性的（R）-构型四元立体中心的关键步骤。7最终，在九个步骤中以8.9％的总收率（er 99.95：0.05）获得了目标产物，从而避免了色谱纯化，并且与初始操作相比具有优势。在从2-氯异烟酸酸41开始的相关“酰胺途径”中，使用仲酰胺指导基团来促进吡啶3-位的邻位锂化。该方案的关键步骤再次包括实际的不对称乙酸羟醛加成（dr = 87:13）。因此，在九个步骤中，仅需进行一次色谱纯化，即可以11.1％的总收率（er> 99.95：0.05）获得DE环结构单元7。
• Isoquinuclidine Mimics ofβ-D-Glucopyranosides: Differences and Similarities in the Mechanism of Action of someβ-D-Glucosidases and aβ-D-Mannosidase
  作者：Matthias Böhm、Edwige Lorthiois、Muthuppalaniappan Meyyappan、Andrea Vasella

  DOI：10.1002/hlca.200390321

  日期：2003.11

  much stronger inhibitor in the manno-series. A consideration of the pKHA values of the isoquinuclidines 1–4 and the pH value of the enzyme assays suggests that the D-gluco-isoquinuclidines are poor mimics of the shape of a reactive, enzyme-bound gluco-conformer, while the D-manno-analogues are reasonably good mimics of a reactive, enzyme-bound manno-conformer. The inhibition results may also suggest

  制备了D-葡萄糖-异喹核苷3和4，并作为来自解糖卡尔多氏菌和甜杏仁的β-葡萄糖苷酶的抑制剂进行了测试。将该结果与D-甘露糖异氰酸核苷1和2对蜗牛β-甘露糖苷酶的抑制作用进行了比较。外消旋系列的探索性实验表明，用苄基醇盐处理酯环氧化物6仅导致差向异构，酯交换反应和环丙烷9的形成。NaN 3还原的环氧化合物13的开环进行区域选择性提供14。用AcOCs处理C（6）O-三氟甲磺酸16引起重排; 与NaN 3的反应得到C（5）-叠氮基衍生物14。然而，乙酰氧基三氟甲磺酸酯18与AcOCs反应，以提供所需的葡萄糖-异喹核苷19。类似地，对映体纯的三氟甲磺酸乙酰氧基酯22提供了D-葡萄糖-异喹核苷24，其被还原和脱保护得到3和4。脱氧类似物30和31通过对22衍生的碘化物27进行还原脱碘获得。的D-葡糖-isoquinuclidines 3,4，30，和31是弱得多的抑制剂的β葡糖苷酶比D-甘露-analogues
• Probing the Conformational Changes in the Enzymatic Hydrolysis of 2-Acetamido-2-deoxy-<i>β</i>-<scp>D</scp>-glucopyranosides
  作者：Matthias Böhm、Andrea Vasella

  DOI：10.1002/hlca.200490229

  日期：2004.10

  d β-d-glucopyranoside; they are competitive inhibitors with Ki values from 0.014 to 0.30 μM. The strong inhibition of these enzymes agrees with the hypothesis that the enzymatic hydrolysis of 2-acetamido-2-deoxy-β-d-glucopyranosides proceeds via a boat-like conformer with a pseudo-axial scissile glycosidic bond and a pseudo-axial acetamido substituent optimally oriented to effect an intramolecular

  合成了异喹核苷7和8，并测试了它们从杰克豆和牛肾脏中作为己糖苷酶的抑制剂。这些异喹核苷模仿了N-乙酰基-葡糖胺衍生的β - d-吡喃葡萄糖苷的1，4- B-构象异构体。它们是具有竞争性抑制剂ķ我值从0.014到0.30μM。这些酶的强抑制与假设同意的酶水解2-乙酰氨基-2-脱氧β -D-吡喃葡萄糖苷前进通过一个船形构象异构体与伪-axial易切断糖苷键和一个伪-轴向乙酰氨基取代基的最佳取向可以实现糖苷配基的分子内取代。
• New Strategy for the Stereoselective Synthesis of Fluorinated β-Amino Acids
  作者：Santos Fustero、Belén Pina、Esther Salavert、Antonio Navarro、M. Carmen Ramírez de Arellano、Antonio Simón Fuentes

  DOI：10.1021/jo025621k

  日期：2002.7.1

  Racemic and chiral nonracemic alpha-substituted and alpha-unsubstituted beta-fluoroalkyl beta-amino acid derivatives 6 and 9 have been synthesized in two steps starting from fluorinated imidoyl chlorides 1 and ester enolates. This approach is based on the chemical reduction of previously obtained gamma-fluorinated beta-enamino esters 4 by using ZnI2/NaBH4 in a nonchelated aprotic medium (dry CH2Cl2) as the reducing agent. A metal-chelated six-membered model has been suggested to explain the stereochemical outcome of the reduction reaction. The process takes place with high yields and with moderate to good diastereoselectivity. The best results related to diastereoselective reduction of chiral beta-enamino esters 4 were provided by the use of (-)-8-phenylmenthol as a chiral auxiliary.