2-benzyl-1-methyl-5-nonylpyrrolidin-3-ol

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-benzyl-1-methyl-5-nonylpyrrolidin-3-ol
• 英文别名: (2R,3S,5S)-2-benzyl-1-methyl-5-nonylpyrrolidin-3-ol
• 化学式: C₂₁H₃₅NO
• 分子量: 317.515
• InChiKey: GBCXKHLKJHRTAB-HBMCJLEFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  23
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-benzyl-1-methyl-5-nonylpyrrolidin-3-ol 在 lithium aluminium tetrahydride 、 (COCl₂)2 、 二甲基亚砜 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 34.0h， 生成 2-benzyl-1-methyl-5-nonylpyrrolidin-3-ol
  参考文献：
  名称：

  Enantioselective Total Synthesis of Either Enantiomer of the Antifungal Antibiotic Preussin (L-657,398) from (S)-Phenylalanine

  摘要：

  Enantioselective total syntheses of the antifungal agent (+)-preussin (1) and its enantiomer (-)-1 from (S)-phenylalanine are described. The central transformations are protic acid-promoted aza-Cope rearrangement-Mannich cyclization reactions (12 --> 19 and 13 --> 27, Schemes 4 and 6). Retro-Mannich fragmentation-Mannich cyclization (27 --> 28, Scheme 6) is key to the formation of (-)-1. This study demonstrates, for the first time, that enantioenriched substituted pyrrolidines can be prepared using the aza-Cope-Mannich rearrangement.

  DOI：

  10.1021/ja00104a005
• 作为产物：
  描述：

  2-十一酮 在 palladium diacetate 、 双(2-二苯基磷苯基)醚 吡啶 、 咪唑 、 sodium hydroxide 、 lithium aluminium tetrahydride 、 正丁基锂 、 二异丙胺 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 正己烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 5.0h， 生成 2-benzyl-1-methyl-5-nonylpyrrolidin-3-ol
  参考文献：
  名称：

  A Concise Stereoselective Synthesis of Preussin, 3-epi-Preussin, and Analogues

  摘要：

  A new stereoselective synthesis of the antifungal and antitumor agents Preussin and 3-epi-Preussin via a Pd-catalyzed carboamination of a protected amino alcohol is described. The key transformation leads to simultaneous formation of the N-C2 bond and the C1'-aryl bond, and allows installation of the aryl group one step from the end of the sequence. This strategy permits the facile construction of a variety of preussin analogues bearing different aromatic groups.

  DOI：

  10.1021/ol0606435

文献信息

• Molecular Iodine-Mediated α-C–H Oxidation of Pyrrolidines to <i>N</i>,<i>O</i>-Acetals: Synthesis of (±)-Preussin by Late-Stage 2,5-Difunctionalizations of Pyrrolidine
  作者：Hao-Jie Rong、Jun-Jun Yao、Ji-Kun Li、Jin Qu

  DOI：10.1021/acs.joc.7b00361

  日期：2017.6.2

  synthesis of unsymmetrical 2,5-disubstituted pyrrolidines from pyrrolidine by two rounds of redox-triggered α-C–H functionalization. Although this approach can be used to introduce substituents at the 2- and 5-positions, it is lengthy because the redox auxiliary must be removed and then reinstalled. Therefore, we sought to develop a method to oxidize 2-functionalized pyrrolidine to cyclic N,O-acetal which

  我们先前报道了通过两轮氧化还原触发的α-C–H官能团由吡咯烷迭代合成不对称的2,5-二取代吡咯烷。尽管此方法可用于在2和5位引入取代基，但它很冗长，因为必须先去除氧化还原助剂然后重新安装。因此，我们寻求开发一种将2-官能化的吡咯烷氧化为环状N，O-乙缩醛的方法，其然后可以与亲核试剂反应以引入5-取代基。在这项工作中，我们发现分子碘可以介导α取代的吡咯烷的仲取代优先于叔α-C–H键的氧化，形成环N，O-缩醛，改善了我们先前报道的方法的步骤经济性。用这种策略，从（±）-吡咯烷丁-3-醇合成（±）-普鲁斯汀及其C（3）差向异构体。
• Short-step Syntheses of All Stereoisomers of Preussin and Their Bioactivities
  作者：Masayuki OKUE、Hidenori WATANABE、Koji KASAHARA、Minoru YOSHIDA、Sueharu HORINOUCHI、Takeshi KITAHARA

  DOI：10.1271/bbb.66.1093

  日期：2002.1

  All the eight stereoisomers of (+)-preussin (1b), an antifungal agent inhibiting the growth of fission yeast and human cancer cells, were synthesized in two steps by non-stereoselective reactions and chromatographic separation, starting from L- and D-N-protected-phenylalaninal (2). Their bioassay revealed all of the stereoisomers to be almost equally bioactive.

  所有八种(+)-普鲁辛（1b）的立体异构体，这是一种抑制裂殖酵母和人类癌细胞生长的抗真菌剂，均通过非立体选择性反应和色谱分离，从L和D保护的苯基丙酰胺（2）起始在两步内合成。生物测定结果显示所有立体异构体的生物活性几乎相同。
• Shimazaki, Makoto; Okazaki, Fumiaki; Nakajima, Fumihiro, Heterocycles, 1993, vol. 36, # 8, p. 1823 - 1836
  作者：Shimazaki, Makoto、Okazaki, Fumiaki、Nakajima, Fumihiro、Ishikawa, Tetsuya、Ohta, Akihiro

  DOI：——

  日期：——
• Three-Step Synthesis of (±)-Preussin from Decanal
  作者：Isac G. Rosset、Rafael M. P. Dias、Vagner D. Pinho、Antonio C. B. Burtoloso

  DOI：10.1021/jo5011558

  日期：2014.7.18

  A straightforward and stereoselective synthesis of the alkaloid preussin is described starting from decanal and diethyl 3-diazo-2-oxopropylphosphonate. The key steps are an aza-Michael reaction from an alpha,beta-unsaturated diazoketone followed by a highly stereoselective Cu-catalyzed ylide formation and then a [1,2]-Stevens rearrangement. This strategy is feasible for extension to preussin analogues, demonstrating its utility for the rapid construction of all-cis-substituted pyrrolidines.
• A Concise and Stereoselective Synthesis of Hydroxypyrrolidines: Rapid Synthesis of (+)-Preussin
  作者：Jason A. Draper、Robert Britton

  DOI：10.1021/ol101631e

  日期：2010.9.17

  A convergent and stereoselective synthesis of 2,5-disubstituted 3-hydroxypyrrolidines has been developed that involves reductive annulation of beta-Iminochlorohydrins, which are readily available from beta-ketochlorohydrins, and provides rapid access to a variety of 2,5-syn-pyrrolidines. Application of this process to the concise (three-step) synthesis of the fungal metabolite (+)-preussin and analogues of this substance is reported.