(-)-1,8a-Diepislaframine | 132486-20-5

• 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: (-)-1,8a-Diepislaframine
• 英文别名: 1,8a-diepislaframine；[(1R,6S,8aR)-6-amino-1,2,3,5,6,7,8,8a-octahydroindolizin-1-yl] acetate
• CAS: 132486-20-5
• 化学式: C₁₀H₁₈N₂O₂
• 分子量: 198.265
• InChiKey: YYIUHLPAZILPSG-IVZWLZJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (-)-1,8a-Diepislaframine 、 乙酸酐 在 吡啶 作用下， 反应 2.0h， 以55%的产率得到Acetic acid (1R,6S,8aR)-6-acetylamino-octahydro-indolizin-1-yl ester
  参考文献：
  名称：

  Enantiomerically Pure Amino Alcohols and Diamino Alcohols from L-Aspartic Acid. Application to the Synthesis of Epi- and Diepislaframine

  摘要：

  Starting from natural aspartic acid (6) a practical method for the synthesis of enantiomerically pure 3-amino alcohols 8 including 3,4-diamino derivatives is described. After perbenzylation of 6 and reduction of both carboxylates, position 4 of the resultant (dibenzylamino)butanediol (11) could be regioselectively blocked to afford the silyloxy-protected intermediate 12a. Functionalization of position 1 was accomplished by nucleophilic displacement reactions including a 2-fold migration of the dibenzylamino substituent or by reductive amination of the amino aldehyde 15. Both routes proceeded under complete preservation of the optical purity. For envisioned SAR studies, we, furthermore, report on the application of this method to a chirospecific synthesis of epi- and diepislaframine (9a and 9b) as diastereomers of the highly bioactive indolizidine alkaloid slaframine (9c). Our first approach including reductive coupling of the chiral amino aldehyde 15 with 5-hydroxypyrrolidine failed when formation of a quaternary ammonium salt occurred, preventing the anticipated anionic cyclization. Therefore, we turned out attention to methodology developed by Wasserman. In fact, introduction of a 3-hydroxypyrrole-2-carboxylate fragment gave a cyclization precursor (30b) which could be successfully transformed into epi- and diepislaframine.

  DOI：

  10.1021/jo00101a042
• 作为产物：
  描述：

  (S)-2--1,5-pentanediol 在 palladium on activated charcoal 吡啶 、 盐酸 、 4-二甲氨基吡啶 、 草酰氯 、 叠氮磷酸二苯酯 、 四丁基氟化铵 、 氢气 、 potassium carbonate 、 二甲基亚砜 、 三乙胺 、 间氯过氧苯甲酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， -78.0~23.0 ℃ 、101.33 kPa 条件下， 反应 162.0h， 生成 (-)-1,8a-Diepislaframine
  参考文献：
  名称：

  A synthesis of (-)-slaframine and (-)-1,8a-diepislaframine

  摘要：

  Reductive cyclization of the optically pure azido epoxides 12 and 13 afforded the indolizidines 14 and 16, which were conveted into (-)-slaframine 1 and (-)-1,8a-diepislaframine 18.

  DOI：

  10.1021/jo00006a002

文献信息

• The chemistry of vicinal tricarbonyls
  作者：Harry H. Wasserman、Chi B. Vu

  DOI：10.1016/0040-4039(94)88384-x

  日期：1994.12

  A synthesis of (±)-slaframine and (±)-6-epi-slaframine is described. The approach makes use of the intramolecular alkylation of an N-substituted 3-hydroxypyrrole-2-carboxylate ester.

  描述了（±）-slaframine和（±）-6-表-slaframine的合成。该方法利用了N-取代的3-羟基吡咯-2-羧酸酯的分子内烷基化。
• Dartmann, Mechthild; Flitsch, Wilhelm; Krebs, Bernt, Liebigs Annalen der Chemie, 1988, p. 695 - 704
  作者：Dartmann, Mechthild、Flitsch, Wilhelm、Krebs, Bernt、Pandl, Klaus、Westfechtel, Alfred

  DOI：——

  日期：——
• Synthesis of (-)-slaframine and related indolizidines
  作者：William H. Pearson、Stephen C. Bergmeier、John P. Williams

  DOI：10.1021/jo00040a045

  日期：1992.7

  An enantioselective synthesis of the indolizidine alkaloid (-)-slaframine 1 is reported. Reductive double cyclization of the azido epoxy tosylate 48 afforded the indolizidine 52, which was converted to (-)-slaframine in two steps. The cyclization substrate 48 was prepared in optically pure form from L-glutamic acid. A similar sequence starting with the epoxide 49 allowed the synthesis of (-)-1,8a-diepislaframine 56. Other routes to slaframine were investigated, often using an intramolecular cycloaddition of an azide with an alkene as a key step. Although these routes did not produce slaframine, they illustrated novel and efficient methods for the assembly of the indolizidine skeleton. Cyclization of the azidodiene 20 afforded the indolizidine 21 in one step as a single diastereomer, presumably a result of a chairlike transition state in the initial dipolar cycloaddition. Desulfurization and deprotection produced (-)-8a-epidesacetoxyslaframine 27. Cyclopropylimine rearrangement of 30 gave the indolizidine 31, which was also converted into (-)-8a-epidesacetoxyslaframine 27. Dipolar cycloaddition of 38 gave the 1-pyrroline 39, which was converted to the indolizidine 40 in one operation using Evans' double alkylation of the 1-metalloenamine derivative of 40. Attempted oxidation of 40 to the ketone 41 was unsuccessful, precluding a reductive amination approach to slaframine.
• PEARSON, WILLIAM H.;BERGMEIER, STEPHEN C., J. ORG. CHEM., 56,(1991) N, C. 1976-1978
  作者：PEARSON, WILLIAM H.、BERGMEIER, STEPHEN C.

  DOI：——

  日期：——
• DARTMANN, MECHTHILD;FLITSCH, WILHELM;KREBS, BERNT;PANDL, KLAUS;WESTFECHTE+, LIEBIGS ANN. CHEM.,(1988) N 7, 695-704
  作者：DARTMANN, MECHTHILD、FLITSCH, WILHELM、KREBS, BERNT、PANDL, KLAUS、WESTFECHTE+

  DOI：——

  日期：——