3-[(1S,2R,3R,7R,10S,11R,13S,14R)-1-methyl-14-propan-2-yl-12-azapentacyclo[8.6.0.02,13.03,7.07,11]hexadecan-2-yl]propanoic acid | 30959-07-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 交让木灵型生物碱
• 英文名称: 3-[(1S,2R,3R,7R,10S,11R,13S,14R)-1-methyl-14-propan-2-yl-12-azapentacyclo[8.6.0.02,13.03,7.07,11]hexadecan-2-yl]propanoic acid
• CAS: 30959-07-0
• 化学式: C₂₂H₃₅NO₂
• 分子量: 345.525
• InChiKey: VWORJFAFBYIQNV-HBLSAEDPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  甲醇 、 3-[(1S,2R,3R,7R,10S,11R,13S,14R)-1-methyl-14-propan-2-yl-12-azapentacyclo[8.6.0.02,13.03,7.07,11]hexadecan-2-yl]propanoic acid 在 硫酸 作用下， 反应 40.0h， 生成 (+/-)-Methyl Homosecodaphniphyllate
  参考文献：
  名称：

  Daphniphyllum alkaloids. 12. A proposed biosynthesis of the pentacylic skeleton. proto-Daphniphylline

  摘要：

  A biosynthetic proposal for the pentacyclic skeleton of the Daphniphyllum alkaloids is put forth (Scheme I) and various ramifications are examined experimentally. proto-Daphniphylline (11), the putative product of this hypothetical biogenesis, has been prepared by a convergent synthesis that starts with amide 14, alpha,beta-unsaturated ester 15, and homogeranyl iodide (Scheme II) and employs a highly efficient tetracyclization process previously used for the synthesis of (+/-)-methyl homosecodaphniphyllate (30) (Scheme III). The structure of proto-daphniphylline was confirmed by converting it into 30. The mechanism of the first stage of the tetracyclization process was investigated with the bis-homoneryl analogues 36/37. Treatment of these aldehydes successively with ammonia and acetic acid provided tetracyclic imine 38, suggesting that the cyclization reaction is a concerted Diels-Alder reaction rather than a stepwise process. Dialdehydes 27/28 were converted into 1,2-dihydro-proto-daphniphylline (29) by a version of the tetracyclization process wherein methylamine (or glycine) is substituted for ammonia. proto-Daphniphylline has also been prepared in a one-pot, two-stage process from the acyclic dialdehydes 51 and 55. Several versions of this pentacyclization process have been worked out. In the simplest, 51 or 55 is treated successively with ammonia and hot acetic acid to afford 11 in 15 +/- 2% yield. A slightly more elaborate protocol, a three-stage process that utilizes NaOH in benzene, ammonia in DMSO, and hot acetic acid, provided 11 in 49.4% overall yield. However, the most efficient pentacyclization process discovered employs successive reactions with methylamine (or glycine) and hot acetic acid. Under these conditions, 17,18-dihydro-proto-daphniphylline (29) is produced in 65% yield. The latter process is one of the most efficient reaction cascades ever discovered; it results in the formation of five rings, four carbon-carbon bonds, two carbon-nitrogen bonds, and concludes with the selective saturation of one of the three double bonds in proto-daphniphylline!

  DOI：

  10.1021/jo00035a009
• 作为产物：
  描述：

  (E)-9-iodo-2,6-dimethylnona-2,6-diene 在 chromium(VI) oxide 、 Wilkinson's catalyst 氢氧化钾 、 草酰氯 、 硫酸 、 ammonium acetate 、 氨 、 水 、 氢气 、 四丁基硫酸氢铵 、 二异丁基氢化铝 、 对甲苯磺酸 、 臭氧 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 二氯甲烷 、 丙酮 、 甲苯 、 苯 为溶剂， 反应 44.67h， 生成 3-[(1S,2R,3R,7R,10S,11R,13S,14R)-1-methyl-14-propan-2-yl-12-azapentacyclo[8.6.0.02,13.03,7.07,11]hexadecan-2-yl]propanoic acid
  参考文献：
  名称：

  Daphniphyllum alkaloids. 12. A proposed biosynthesis of the pentacylic skeleton. proto-Daphniphylline

  摘要：

  A biosynthetic proposal for the pentacyclic skeleton of the Daphniphyllum alkaloids is put forth (Scheme I) and various ramifications are examined experimentally. proto-Daphniphylline (11), the putative product of this hypothetical biogenesis, has been prepared by a convergent synthesis that starts with amide 14, alpha,beta-unsaturated ester 15, and homogeranyl iodide (Scheme II) and employs a highly efficient tetracyclization process previously used for the synthesis of (+/-)-methyl homosecodaphniphyllate (30) (Scheme III). The structure of proto-daphniphylline was confirmed by converting it into 30. The mechanism of the first stage of the tetracyclization process was investigated with the bis-homoneryl analogues 36/37. Treatment of these aldehydes successively with ammonia and acetic acid provided tetracyclic imine 38, suggesting that the cyclization reaction is a concerted Diels-Alder reaction rather than a stepwise process. Dialdehydes 27/28 were converted into 1,2-dihydro-proto-daphniphylline (29) by a version of the tetracyclization process wherein methylamine (or glycine) is substituted for ammonia. proto-Daphniphylline has also been prepared in a one-pot, two-stage process from the acyclic dialdehydes 51 and 55. Several versions of this pentacyclization process have been worked out. In the simplest, 51 or 55 is treated successively with ammonia and hot acetic acid to afford 11 in 15 +/- 2% yield. A slightly more elaborate protocol, a three-stage process that utilizes NaOH in benzene, ammonia in DMSO, and hot acetic acid, provided 11 in 49.4% overall yield. However, the most efficient pentacyclization process discovered employs successive reactions with methylamine (or glycine) and hot acetic acid. Under these conditions, 17,18-dihydro-proto-daphniphylline (29) is produced in 65% yield. The latter process is one of the most efficient reaction cascades ever discovered; it results in the formation of five rings, four carbon-carbon bonds, two carbon-nitrogen bonds, and concludes with the selective saturation of one of the three double bonds in proto-daphniphylline!

  DOI：

  10.1021/jo00035a009

文献信息

• Daphnezomines L, M, N, and O, new alkaloids from Daphniphyllum humile
  作者：Hiroshi Morita、Jun'ichi Kobayashi

  DOI：10.1016/s0040-4020(02)00737-8

  日期：2002.8

  Four new alkaloids, daphnezomines L-O (1-4), have been isolated from the stems of Daphniphyllum humile, and the structures and the relative stereochemistry were elucidated on the basis of spectroscopic data. The structure of daphnezomine L (1) was close to that of a biogenetic intermediate from secodaphnane to daphnane skeletons proposed previously. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Daphniphyllum alkaloids. 12. A proposed biosynthesis of the pentacylic skeleton. proto-Daphniphylline
  作者：Clayton H. Heathcock、Serge Piettre、Roger B. Ruggeri、John A. Ragan、John C. Kath

  DOI：10.1021/jo00035a009

  日期：1992.4

  A biosynthetic proposal for the pentacyclic skeleton of the Daphniphyllum alkaloids is put forth (Scheme I) and various ramifications are examined experimentally. proto-Daphniphylline (11), the putative product of this hypothetical biogenesis, has been prepared by a convergent synthesis that starts with amide 14, alpha,beta-unsaturated ester 15, and homogeranyl iodide (Scheme II) and employs a highly efficient tetracyclization process previously used for the synthesis of (+/-)-methyl homosecodaphniphyllate (30) (Scheme III). The structure of proto-daphniphylline was confirmed by converting it into 30. The mechanism of the first stage of the tetracyclization process was investigated with the bis-homoneryl analogues 36/37. Treatment of these aldehydes successively with ammonia and acetic acid provided tetracyclic imine 38, suggesting that the cyclization reaction is a concerted Diels-Alder reaction rather than a stepwise process. Dialdehydes 27/28 were converted into 1,2-dihydro-proto-daphniphylline (29) by a version of the tetracyclization process wherein methylamine (or glycine) is substituted for ammonia. proto-Daphniphylline has also been prepared in a one-pot, two-stage process from the acyclic dialdehydes 51 and 55. Several versions of this pentacyclization process have been worked out. In the simplest, 51 or 55 is treated successively with ammonia and hot acetic acid to afford 11 in 15 +/- 2% yield. A slightly more elaborate protocol, a three-stage process that utilizes NaOH in benzene, ammonia in DMSO, and hot acetic acid, provided 11 in 49.4% overall yield. However, the most efficient pentacyclization process discovered employs successive reactions with methylamine (or glycine) and hot acetic acid. Under these conditions, 17,18-dihydro-proto-daphniphylline (29) is produced in 65% yield. The latter process is one of the most efficient reaction cascades ever discovered; it results in the formation of five rings, four carbon-carbon bonds, two carbon-nitrogen bonds, and concludes with the selective saturation of one of the three double bonds in proto-daphniphylline!