benzyl (S)-2-(2(R)-methyloxiranyl)-1-pyrrolidinecarboxylate | 77733-65-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzyl (S)-2-(2(R)-methyloxiranyl)-1-pyrrolidinecarboxylate
• 英文别名: benzyl (2S)-2-[(2R)-2-methyloxiran-2-yl]pyrrolidine-1-carboxylate
• CAS: 77733-65-4
• 化学式: C₁₅H₁₉NO₃
• 分子量: 261.321
• InChiKey: DKZROOJWYSBDHN-ZFWWWQNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  42.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  benzyl (S)-2-(2(R)-methyloxiranyl)-1-pyrrolidinecarboxylate 在 氢氧化钾 、 lithium aluminium tetrahydride 、 聚合甲醛 、 草酰氯 、 camphor-10-sulfonic acid 、 氨 、 甲基锂 、 lithium 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 180.0h， 生成 Pumiliotoxin B
  参考文献：
  名称：

  Enantioselective total syntheses of pumiliotoxin B and pumiliotoxin 251D. A general entry to the pumiliotoxin A alkaloids via stereospecific iminium ion-vinylsilane cyclizations

  摘要：

  DOI：

  10.1021/ja00327a022
• 作为产物：
  描述：

  Boc-L-脯氨酸甲酯 在 N-碘代丁二酰亚胺 、 氯化亚砜 、 水 、 三乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 二氯甲烷 为溶剂， 反应 43.0h， 生成 benzyl (S)-2-(2(R)-methyloxiranyl)-1-pyrrolidinecarboxylate
  参考文献：
  名称：

  通过O定向炔烃自由基氢化对映体对虾（Dendrobatidae）蛙毒素（+）-pumiliotoxin B的对映选择性正式全合成

  摘要：

  在这里，我们描述了我们的双取代的烷基乙炔（含Ph 3 SnH和Et 3 B）的O方向自由基氢锡烷化在（+）-pumiliotoxin B总合成问题中的应用。具体而言，我们报道了该方法在Overman炔烃8的合成中的使用，从而首次证明了该方法在复杂的天然产物全合成环境中的巨大效用。我们还报告在这里上一个新的，立体控制，具有很强的实用性对映选择性途径超人的吡咯烷环氧伙伴9为8，克服了以前使用制备型HPLC分离9的原始合成中获得的非对映体环氧化物的1：1混合物的要求。

  DOI：

  10.1016/j.tetlet.2010.10.141

文献信息

• Efficient Total Syntheses of Pumiliotoxins A and B. Applications of Iodide-Promoted Iminium Ion−Alkyne Cyclizations in Alkaloid Construction
  作者：Nan-Horng Lin、Larry E. Overman、Michael H. Rabinowitz、Leslie A. Robinson、Matthew J. Sharp、Jeffery Zablocki

  DOI：10.1021/ja961641q

  日期：1996.1.1

  A practical route for the total synthesis of pumiliotoxin A alkaloids is described. The central step is formation of the piperidine ring and establishment of the (Z)-alkylidene side chain by an iodide-promoted iminium ion−alkyne cyclization. The total synthesis of (+)-15(S)-pumiliotoxin A (2) was realized in 5 steps and 32% overall yield from alkyne 36 and epoxide 7. This synthesis of 2 proceeded in

  描述了 pumiliotoxin A 生物碱全合成的实用路线。中心步骤是通过碘化物促进的亚胺鎓离子-炔环化作用形成哌啶环和建立 (Z)-亚烷基侧链。(+)-15(S)-pumiliotoxin A (2) 的全合成分 5 步实现，炔烃 36 和环氧化物 7 的总产率为 32%。2 的合成分 13 步进行，总产率为 12%（ S)-2-甲基-1-戊烯-3-醇 (25) 和 8 个步骤和来自 N-[(苄氧基) 羰基]-1-脯氨酸的 9% 总产率。(+)-pumiliotoxin B (3) 的合成以四步类似的方式实现，来自炔烃 54 和环氧化物 7 的总产率为 44%。对映纯 3 的总产率为 8%，来自 N-[(苄氧基)羰基]-l -脯氨酸和 10% 来自 (4S,5R)-4-methyl-5-phenyl-2-oxazolidinone。
• Total Synthesis of Pumiliotoxins 209F and 251D via Late-Stage, Nickel-Catalyzed Epoxide−Alkyne Reductive Cyclization
  作者：Katrina S. Woodin、Timothy F. Jamison

  DOI：10.1021/jo071132e

  日期：2007.9.1

  Pumiliotoxins 209F and 251D were synthesized using highly selective nickel-catalyzed epoxide−alkyne reductive cyclizations as the final step. The exocyclic (Z)-alkene found in the majority of the pumiliotoxins was formed stereospecifically and regioselectively, without the use of a directing group on the alkyne, and the epoxide underwent ring opening exclusively at the less hindered carbon to provide

  铝毒素209F和251D使用高度选择性的镍催化环氧化物炔还原环化反应作为最终步骤合成。在大多数pumiliotoxins毒素中发现的环外（Z）烯烃是立体定向和区域选择性形成的，无需在炔烃上使用导向基团，并且环氧化物仅在受阻较小的碳上开环以提供所需的叔醇。使用非对映选择性地将sulf代氧鎓阴离子加到脯氨酸衍生的甲基酮中来制备环氧化物。
• Enantioselective total synthesis of the pumiliotoxin a alkaloids via reductive iminium ion-alkyne cyclizations. Total synthesis of (+)-pumiliotoxin a
  作者：Larry E. Overman、Matthew J. Sharp

  DOI：10.1016/s0040-4039(00)82477-6

  日期：1988.1

  A highly practical new route for the enantioselective synthesis of the pumiliotoxin A alkaloids in which the title reaction is a key step is disclosed.

  公开了一种对映选择性合成pumiliotoxin A生物碱的高度实用的新途径，其中标题反应是关键步骤。
• Carbonyl participation in the reaction of N-acyl-2-isopropenylpyrrolidines with halogen electrophiles. Stereocontrolled preparation of enantiomerically pure synthons for the synthesis of pumiliotoxin A alkaloids.
  作者：Larry E. Overman、Russell J. McCready

  DOI：10.1016/s0040-4039(00)85739-1

  日期：1982.1

  Allylic carbamate 4 and allylic benzamide 12 react with halogen electrophiles with high 1,2-relative asymmetric induction via carbonyl participation.

  烯丙基氨基甲酸酯4和烯丙基苯甲酰胺12与卤素亲电试剂通过羰基参与以高1,2-相对不对称诱导反应。
• A new class of cardiotonic agents: structure-activity correlations for natural and synthetic analogs of the alkaloid pumiliotoxin B (8-hydroxy-8-methyl-6-alkylidene-1-azabicyclo[4.3.0]nonanes)
  作者：J. W. Daly、E. T. McNeal、L. E. Overman、D. H. Ellison

  DOI：10.1021/jm00382a017

  日期：1985.4

  Pumiliotoxin B (PTX-B, 6-(6',7'-dihydroxy-2',5'-dimethyl-(E)-4'-octenylidene)-8-hydroxy-8 -methyl-1- azabicyclo-[4.3.0] nonane) increases the force of contractures of spontaneously beating guinea pig atrial strips by 3- to 5-fold with half-maximal effects at about 3 microM and increases rates of atrial contractions by 2- to 3-fold with half-maximal effects at about 6 microM. The presence of an axial 7-hydroxy substituent (PTX 339A) decreases the efficacy but not the potency of PTX-B as a positive inotropic agent while having only slight effects on activity as a positive chronotropic agent. The presence of an equatorial 7-hydroxy substituent (PTX 339B) greatly decreases efficacy and potency of PTX-B as a positive chronotropic and inotropic agent. Pumiliotoxin A which lacks the side-chain 7'-hydroxy group of PTX-B causes only a 2-fold increase in force of contracture at 54 microM while having minimal effects on rate. The presence of an axial 7-hydroxy substituent (PTX 323B' and 323B", epimeric at the 6'-hydroxy) markedly enhances positive inotropic and chronotropic effects of PTX-A. Another congener, PTX 251D with a 6-(2'-methylhexylidene) side chain, and a synthetic analogue with a 6-(6'-heptenylidene) side chain are cardiac depressants. Both lack hydroxyl groups in the side chain. The presence of an omega-1 hydroxy group in the side chain of PTX 251D yields an alkaloid (267C) with weak positive inotropic effects and minimal chronotropic effects. The presence of an axial 7-hydroxy group in the indolizidine ring of PTX 251D results in a compound (PTX 267A) with very weak positive inotropic effects while retaining the negative chronotropic effects of PTX 251D. A synthetic analogue with a 6-(7'-hydroxyheptylidene) side chain is a cardiac depressant even though it contains a side-chain hydroxyl corresponding in position to the 7'-hydroxyl of the side chain of PTX-B. The positive chronotropic and inotropic effects of pumiliotoxin B are reversed only by relatively high concentrations of the calcium channel blockers nifedipine and verapamil, suggesting that pumiliotoxin B may owe its cardiotonic activities to effects on internal mobilization of calcium.