(3aR,9R,9aR,9bS)-octahydro-2,2-dimethyl-9-(phenylmethoxy)-1,3-dioxolo[4,5-a]indolizine | 154815-12-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚里西啶
• 英文名称: (3aR,9R,9aR,9bS)-octahydro-2,2-dimethyl-9-(phenylmethoxy)-1,3-dioxolo[4,5-a]indolizine
• 英文别名: (1S,2R,8R,8aR)-8-(benzyloxy)-1,2-(isopropylidenedioxy)octahydroindolizine；(1S,2R,8R,8aR)-8-(benzyloxy)-1,2-(isopropylidenedioxy)indolizidine；(1S,2R,8R,8aR)-8-benzyloxy-1,2-isopropylidenedioxyindolizidine；(3aR,9R,9aR,9bS)-2,2-dimethyl-9-phenylmethoxy-3a,4,6,7,8,9,9a,9b-octahydro-[1,3]dioxolo[4,5-a]indolizine
• CAS: 154815-12-0
• 化学式: C₁₈H₂₅NO₃
• 分子量: 303.401
• InChiKey: HCJFXNSKTMCSCN-QBPKDAKJSA-N

物化性质

• 沸点：
  397.2±42.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3aR,9R,9aR,9bS)-octahydro-2,2-dimethyl-9-(phenylmethoxy)-1,3-dioxolo[4,5-a]indolizine 在 palladium dichloride 盐酸 、 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 14.5h， 生成 八倾吲嗪三醇
  参考文献：
  名称：

  New Chiral Route to (-)-Swainsonine via an Aqueous Acylnitroso Cycloaddition Approach

  摘要：

  A new noncarbohydrate-based enantioselective approach to (-)-swainsonine (1) is described, in which the aqueous intramolecular Diels-Alder reaction of a chiral acylnitroso diene has been employed as a key reaction. The intramolecular cycloaddition of the chiral hydroxamic acid 9, available from D-malic acid in 10 steps, with Pr4NIO4 was conducted under the conventional nonaqueous conditions using CHCl3 as a solvent, whereupon intermediacy acylnitroso compound 10 cyclized spontaneously to give the trans- and cis-1,2-oxazinolactams 11 and 12 with a low diastereoselction of 1.3:1 in 76 % combined yield. When the corresponding reaction was performed in water, it led to significant enhancements of trans selectivity of 4.1:1 as well as combined yield (89%). The trans adduct 11 was subjected to reductive N-O bond cleavage followed by diastereoselective hydroxylation with OsO4 to provide the 1,2-glycol 21, which was then converted to the amino alcohol 25. Intramolecular cyclodehydration of 25 with CBr4/PPhs/Et3N and subsequent deprotection furnished (-)-swainsonine (1).

  DOI：

  10.1021/jo00085a026
• 作为产物：
  描述：

  (2R,4R)-4-formyl-2-phenyl-1,3-dioxane 在 吡啶 、 咪唑 、 氢氧化钾 、 sodium hydroxide 、 sodium periodate 、 disodium hydrogenphosphate 、 sodium amalgam 、 四氧化锇 、 lithium aluminium tetrahydride 、 四溴化碳 、 盐酸羟胺 、 potassium tert-butylate 、 碘 、 4-甲基苯磺酸吡啶 、 二异丁基氢化铝 、 N-甲基吗啉氧化物 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 乙腈 、 苯 为溶剂， 反应 48.25h， 生成 (3aR,9R,9aR,9bS)-octahydro-2,2-dimethyl-9-(phenylmethoxy)-1,3-dioxolo[4,5-a]indolizine
  参考文献：
  名称：

  New Chiral Route to (-)-Swainsonine via an Aqueous Acylnitroso Cycloaddition Approach

  摘要：

  A new noncarbohydrate-based enantioselective approach to (-)-swainsonine (1) is described, in which the aqueous intramolecular Diels-Alder reaction of a chiral acylnitroso diene has been employed as a key reaction. The intramolecular cycloaddition of the chiral hydroxamic acid 9, available from D-malic acid in 10 steps, with Pr4NIO4 was conducted under the conventional nonaqueous conditions using CHCl3 as a solvent, whereupon intermediacy acylnitroso compound 10 cyclized spontaneously to give the trans- and cis-1,2-oxazinolactams 11 and 12 with a low diastereoselction of 1.3:1 in 76 % combined yield. When the corresponding reaction was performed in water, it led to significant enhancements of trans selectivity of 4.1:1 as well as combined yield (89%). The trans adduct 11 was subjected to reductive N-O bond cleavage followed by diastereoselective hydroxylation with OsO4 to provide the 1,2-glycol 21, which was then converted to the amino alcohol 25. Intramolecular cyclodehydration of 25 with CBr4/PPhs/Et3N and subsequent deprotection furnished (-)-swainsonine (1).

  DOI：

  10.1021/jo00085a026

文献信息

• A new approach to indolizidine alkaloids: Asymmetric formal total synthesis of (−)-Swainsonine
  作者：Zhou Wei-Shan、Xie Wen-Ge、Lu Zhi-Hui、Pan Xin-Fu

  DOI：10.1016/0040-4039(95)00058-k

  日期：1995.2

  A concise, noncarbohydrate-based approach to (−)-Swainsonine (1) has been achieved by utilizing the kinetic resolution of the α-furfuryl amide 4 and the Sharpless ADH reaction as key steps.

  通过利用α-糠基酰胺4的动力学拆分和Sharpless ADH反应作为关键步骤，已经获得了一种简洁的，基于非碳水化合物的（-）-Swainsonine（1）方法。
• Asymmetric Synthesis of (−)-Swainsonine, (+)-1,2-Di-<i>epi</i>-swainsonine, and (+)-1,2,8-Tri-<i>epi</i>-swainsonine
  作者：Karl B. Lindsay、Stephen G. Pyne

  DOI：10.1021/jo025977w

  日期：2002.11.1

  The asymmetric synthesis of H-swainsonine via a nonchiral pool route that involves the Sharpless epoxidation to induce chirality is reported. The key steps involve vinyl epoxide aminolysis, ring-closing metathesis, and intramolecular N-alkylation to prepare the indolizidine ring and a highly diastereoselective cis-dihydroxylation using AD-mix-cc. This synthetic strategy also allowed for the diastereoselective synthesis of (+)-1,2-di-epi-swainsonine and (+)-1,2,8-tri-epi-swainsonine.
• Allylated Monosaccharides as Precursors in Triple Reductive Amination Strategies:  Synthesis of Castanospermine and Swainsonine
  作者：Hang Zhao、Sunej Hans、Xuhong Cheng、David R. Mootoo

  DOI：10.1021/jo001447t

  日期：2001.3.1

  The feasibility of the triple-reductive amination reaction for the synthesis of complex indolizidine frameworks is illustrated by application to the potent glycosidase inhibitors castanospermine and swainsonine. The target compounds were obtained from known carbohydrate precursors in yields of 23 and 14%, over nine and 13 steps, respectively. The iodoetherification reaction of allylated monosaccharides was shown to be a practical reaction for the synthesis of the tricarbonyl precursors for the key triple reductive amination reactions.
• General Approach to Glycosidase Inhibitors. Enantioselective Synthesis of Deoxymannojirimycin and Swainsonine
  作者：Rubén Martín、Caterina Murruzzu、Miquel A. Pericàs、Antoni Riera

  DOI：10.1021/jo048172s

  日期：2005.3.1

  Deoxymannojirimycin (2) and swainsonine (4) have been synthesized from each enantiomer of the same bicyclic carbamate precursor 7. The key intermediate was prepared by a simple and efficient three-step synthesis involving RCM of the diene 8, which in turn is easily accessible in any configuration from enantiomerically enriched 2,3-epoxy-4-penten-1-ol 9.
• Zhou, Wei-Shan; Xie, Wen-Ge; Lu, Zhi-Hui, Journal of the Chemical Society. Perkin transactions I, 1995, # 20, p. 2599 - 2604
  作者：Zhou, Wei-Shan、Xie, Wen-Ge、Lu, Zhi-Hui、Pan, Xin-Fu

  DOI：——

  日期：——