(+/-)-3,4-Didehydrohomodaphniphyllic acid | 138515-97-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (+/-)-3,4-Didehydrohomodaphniphyllic acid
• CAS: 138515-97-6
• 化学式: C₂₂H₃₃NO₂
• 分子量: 343.51
• InChiKey: OUAAEVIHJMLJLC-XUAMWXHYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.48
• 重原子数：
  25.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  40.54
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (+/-)-3,4-Didehydrohomodaphniphyllic acid 在 Rh/Al₂O₃ 盐酸 、 氢气 作用下， 以 甲苯 为溶剂， 120.0 ℃ 、12.41 MPa 条件下， 反应 44.0h， 生成 (+/-)-Methyl-3-epihomodaphniphyllate
  参考文献：
  名称：

  Daphniphyllum alkaloids. 10. Classical total synthesis of methyl homodaphniphyllate

  摘要：

  Details for the first total synthesis of a Daphniphyllum alkaloid are presented. The synthesis required a total of 15 steps from the known keto acid 4 and followed the course 4 --> 10 --> 11 --> 16 --> 20 --> 24 --> 25 --> 27 --> 29 --> 36 --> 46 --> 47 --> 48 --> 49 --> (+/-)-2; the overall yield was about 1.1%. The first three rings were assembled from keto acid 4 and ketal amine 8, which were coupled to form amide 10. This material was isomerized under acidic conditions to the tricyclic ketal lactam 11. The masked propionic acid side chain was introduced by alkylation of the lithium enolate of 11 to give 16. Although the remaining skeletal carbons could be added to 16 in a Michael addition of its lithium enolate to enone 13, keto amide 17 could not be cyclized to the desired tetracyclic system. However, the related keto thioamide 24, lacking the isopropyl group, was smoothly cyclized to the tetracyclic, vinylogous amide 25. Enone 25 was transformed into its isomer, 29, by a four-step sequence of steps. Treatment of 29 with aqueous acid caused hydrolysis of the ketal and aldolization to give 30, which was isomerized to 31 under basic conditions. Compound 31 was the first synthetic material having the characteristic pentacyclic skeleton of daphniphylline. For introduction of the remaining carbons, the lithium enolate 29 was treated with acetaldehyde, and the resulting aldol subjected to strongly acidic conditions to obtain the desired pentacycle 36, accompanied by a small amount of the hexacyclic byproduct 37. The final carbon could be installed by addition of lithium dimethylcopper to 36, but the product was a mixture of the diastereomeric diketones 43 and 44. These two isomers were found to be in facile equilibrium, even under chromatographic conditions. Furthermore, we were unable to remove the carbonyl groups, apparently because one of the carbonyl groups is exceedingly hindered. Therefore, the final carbon was added and the carbonyl groups removed by an indirect method. The enolate ion resulting from the cuprate reaction on 36 was trapped with diethyl phosphorochloridate to obtain enol phosphate 46. After converting the other carbonyl group into an enol phosphate, compound 47 was subjected to lithium in ethylamine to cleave the two vinyl phosphate groups and the benzyl group. In addition, one of the two double bonds was reduced; compound 48 was obtained in 64% yield. The remaining double bond proved to be very resistant to catalytic hydrogenation conditions; reduction occurred only at high pressure (1800 psi), high temperature (120-degrees-C), and long reaction time (20 h). With Rh on Al2O3, amino ester 50 gave completely the undesired stereochemistry, affording 51. However, Pearlman's catalyst, Pd(OH)2 on carbon, gave a 1:1 mixture of the two isomers when these conditions were applied to amino acid 49 in methanolic solution; 51 and racemic methyl homodaphniphyllate ((+/-)-2) were formed in a ratio of 1:1. The two isomers are readily separated by silica gel chromatography.

  DOI：

  10.1021/jo00035a007
• 作为产物：
  描述：

  在 盐酸 、 六甲基磷酰三胺 、 sodium tetrahydroborate 、 2,6-二叔丁基吡啶 、 jones' reagent 、 硫酸 、 2,2,6,6-tetramethylpiperidinyl-lithium 、 triethyloxonium fluoroborate 、 4-甲基苯磺酸吡啶 、 lithium 、 乙胺 、 溶剂黄146 、 三乙胺 、 间氯过氧苯甲酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 丙酮 、 叔丁醇 、 苯 为溶剂， 反应 267.64h， 生成 (+/-)-3,4-Didehydrohomodaphniphyllic acid
  参考文献：
  名称：

  Daphniphyllum alkaloids. 10. Classical total synthesis of methyl homodaphniphyllate

  摘要：

  Details for the first total synthesis of a Daphniphyllum alkaloid are presented. The synthesis required a total of 15 steps from the known keto acid 4 and followed the course 4 --> 10 --> 11 --> 16 --> 20 --> 24 --> 25 --> 27 --> 29 --> 36 --> 46 --> 47 --> 48 --> 49 --> (+/-)-2; the overall yield was about 1.1%. The first three rings were assembled from keto acid 4 and ketal amine 8, which were coupled to form amide 10. This material was isomerized under acidic conditions to the tricyclic ketal lactam 11. The masked propionic acid side chain was introduced by alkylation of the lithium enolate of 11 to give 16. Although the remaining skeletal carbons could be added to 16 in a Michael addition of its lithium enolate to enone 13, keto amide 17 could not be cyclized to the desired tetracyclic system. However, the related keto thioamide 24, lacking the isopropyl group, was smoothly cyclized to the tetracyclic, vinylogous amide 25. Enone 25 was transformed into its isomer, 29, by a four-step sequence of steps. Treatment of 29 with aqueous acid caused hydrolysis of the ketal and aldolization to give 30, which was isomerized to 31 under basic conditions. Compound 31 was the first synthetic material having the characteristic pentacyclic skeleton of daphniphylline. For introduction of the remaining carbons, the lithium enolate 29 was treated with acetaldehyde, and the resulting aldol subjected to strongly acidic conditions to obtain the desired pentacycle 36, accompanied by a small amount of the hexacyclic byproduct 37. The final carbon could be installed by addition of lithium dimethylcopper to 36, but the product was a mixture of the diastereomeric diketones 43 and 44. These two isomers were found to be in facile equilibrium, even under chromatographic conditions. Furthermore, we were unable to remove the carbonyl groups, apparently because one of the carbonyl groups is exceedingly hindered. Therefore, the final carbon was added and the carbonyl groups removed by an indirect method. The enolate ion resulting from the cuprate reaction on 36 was trapped with diethyl phosphorochloridate to obtain enol phosphate 46. After converting the other carbonyl group into an enol phosphate, compound 47 was subjected to lithium in ethylamine to cleave the two vinyl phosphate groups and the benzyl group. In addition, one of the two double bonds was reduced; compound 48 was obtained in 64% yield. The remaining double bond proved to be very resistant to catalytic hydrogenation conditions; reduction occurred only at high pressure (1800 psi), high temperature (120-degrees-C), and long reaction time (20 h). With Rh on Al2O3, amino ester 50 gave completely the undesired stereochemistry, affording 51. However, Pearlman's catalyst, Pd(OH)2 on carbon, gave a 1:1 mixture of the two isomers when these conditions were applied to amino acid 49 in methanolic solution; 51 and racemic methyl homodaphniphyllate ((+/-)-2) were formed in a ratio of 1:1. The two isomers are readily separated by silica gel chromatography.

  DOI：

  10.1021/jo00035a007