(8R,8aS)-3-methyl-5-indolizidinone | 152230-88-1

• 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: (8R,8aS)-3-methyl-5-indolizidinone
• 英文别名: (8R,8aS)-8-methylhexahydroindolizin-5-one；(8R,9S)-(-)-hexahydro-8-methyl-5-indolizinone；(8R,8aS)-hexahydro-8-methyl-5(1H)-indolizinone；(8R,8aS)-8-methylhexahydroindolizin-5(1H)-one；(8R,8aS)-8-methyl-2,3,6,7,8,8a-hexahydro-1H-indolizin-5-one
• CAS: 152230-88-1
• 化学式: C₉H₁₅NO
• 分子量: 153.224
• InChiKey: GDVVFVRMOYOIJR-SFYZADRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (8R,8aS)-3-methyl-5-indolizidinone 在 sodium cyanoborohydride 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 (-)-indolizidine 209B
  参考文献：
  名称：

  A chiral synthesis of (8R,8aS)-hexahydro-8-methyl-5(1H)-indolizinone

  摘要：

  The enantioselective synthesis of (8R,8aS)-hexahydro-8-methyl-5(1H)-indolizinone ((-)-13), which is a synthetic intermediate of 5,8-disubstituted indolizidine alkaloids has been carried out. Reaction of ethyl (E)-(4R, 5R)-8-benzyloxy-4, 5-epoxy-4-methyl-2-octenoate (4) with formic acid in the presence of Pd2(dba)3CHCl3 and n-Bu3P as a catalyst gave ethyl (E)-(4R, 5R)-8-benzyloxy-5-hydroxy-4-methyl-2-octenoate (5), which was converted to (-)-13 in 8 steps.

  DOI：

  10.1016/s0957-4166(00)80326-2
• 作为产物：
  描述：

  (2R,3S)-ethyl 1-allyl-3-hydroxy-6-oxopiperidine-2-carboxylate 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 bis(2-methoxyethyl) azodicarboxylate 、 copper(l) iodide 、 正丁基锂 、 草酰氯 、 Lipase PL 、 palladium 10% on activated carbon 、 氢气 、 三乙基硼氢化锂 、 二甲基亚砜 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 二氯甲烷 、 甲基叔丁基醚 、 乙酸乙酯 为溶剂， -78.0~20.0 ℃ 、101.33 kPa 条件下， 反应 56.58h， 生成 (8R,8aS)-3-methyl-5-indolizidinone
  参考文献：
  名称：

  8-脱氧铝毒素193H和9-脱氧铝毒素207O的合成

  摘要：

  从（+）-和（-）- 10的对映体开始，已经实现了8-脱氧铝毒素193H和9-脱氧铝毒素207O的不对称合成。对映体纯的醇（+）-和（-）- 10是通过脂肪酶介导的外消旋体10的动力学拆分而获得的，外消旋体10是由新内酰胺型结构单元（-）- 8以3个步骤以高度立体选择性的方式制备的。

  DOI：

  10.1016/j.tetlet.2018.09.015

文献信息

• A concise asymmetric synthesis of 5,8-disubstituted indolizidine alkaloids. Total synthesis of (−)-indolizidine 209B
  作者：Yongcheng Song、Sentaro Okamoto、Fumie Sato

  DOI：10.1016/s0040-4039(02)02149-4

  日期：2002.11

  A general access to 5,8-disubstituted indolizidine alkaloids has been developed, where the asymmetric addition of an optically active allenyltitanium to benzyl[4-(tert-butyldimethylsilyloxy)butylidene]amine (2) is the key reaction. As a typical example, (−)-indolizidine 209B was efficiently synthesized in 40% overall yield in a five-step reaction starting from readily available (S)-1-methyl-3-trim

  已经开发了普遍获得的5,8-二取代的吲哚并咪唑生物碱，其中将光学活性的烯丙基钛不对称地添加至苄基[4-（叔丁基二甲基甲硅烷氧基）丁烯基]胺（2）是关键反应。作为典型的例子，（ - ） -吲哚里209B在40％总产率有效地合成从容易获得的（起始五步反应小号）-1-甲基-3- trimethylsilylprop -2-炔基酯（1）。
• Aube, Jeffrey; Rafferty, Pat S.; Milligan, Gregory L., Heterocycles, 1993, vol. 35, # 2, p. 1141 - 1147
  作者：Aube, Jeffrey、Rafferty, Pat S.、Milligan, Gregory L.

  DOI：——

  日期：——
• Stereoselective synthesis of (8R,8aS)-8-methylhexahydroindolizin-5-one
  作者：Paul Armstrong、Gavin O’Mahony、Paul J. Stevenson、Andrew D. Walker

  DOI：10.1016/j.tetlet.2005.09.133

  日期：2005.11

  Catalytic hydrogenation of dihydroindolizidinone occurred preferentially from the endo-face giving rapid entry to (8R,8aS)-8-methylhexahydroindolizin-5-one, a key intermediate in the synthesis of 5,8-disubstituted indolizidines and deoxypumiliotoxin 25 1 H. The selectivity could be improved further by diimide reduction though this also resulted in some oxidation of the alkene to the diene. The basis of the unusual stereoselectivity in the diimide reduction is believed to be stereoelectronic in origin. (c) 2005 Elsevier Ltd. All rights reserved.
• Synthesis of 8-deoxypumiliotoxin 193H and 9-deoxyhomopumiliotoxin 207O
  作者：Takuya Okada、Taiga Yamamoto、Daiki Kato、Masashi Kawasaki、Ralph A. Saporito、Naoki Toyooka

  DOI：10.1016/j.tetlet.2018.09.015

  日期：2018.10

  The asymmetric synthesis of 8-deoxypumiliotoxin 193H and 9-deoxyhomopumiliotoxin 207O has been achieved, starting from both enantiomers of (+)- and (−)-10. Enantiomerically pure alcohols (+)- and (−)-10 were obtained by lipase-mediated kinetic resolution of racemic 10, which was prepared in 3 steps from new lactam-type building block (−)-8 in a highly stereoselective manner.

  从（+）-和（-）- 10的对映体开始，已经实现了8-脱氧铝毒素193H和9-脱氧铝毒素207O的不对称合成。对映体纯的醇（+）-和（-）- 10是通过脂肪酶介导的外消旋体10的动力学拆分而获得的，外消旋体10是由新内酰胺型结构单元（-）- 8以3个步骤以高度立体选择性的方式制备的。
• A chiral synthesis of (8R,8aS)-hexahydro-8-methyl-5(1H)-indolizinone
  作者：Akiharu Satake、Isao Shimizu

  DOI：10.1016/s0957-4166(00)80326-2

  日期：1993.7

  The enantioselective synthesis of (8R,8aS)-hexahydro-8-methyl-5(1H)-indolizinone ((-)-13), which is a synthetic intermediate of 5,8-disubstituted indolizidine alkaloids has been carried out. Reaction of ethyl (E)-(4R, 5R)-8-benzyloxy-4, 5-epoxy-4-methyl-2-octenoate (4) with formic acid in the presence of Pd2(dba)3CHCl3 and n-Bu3P as a catalyst gave ethyl (E)-(4R, 5R)-8-benzyloxy-5-hydroxy-4-methyl-2-octenoate (5), which was converted to (-)-13 in 8 steps.