Cyclopropanecarboxylic acid 1-methyl-2-oxo-cyclopentylmethyl ester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Cyclopropanecarboxylic acid 1-methyl-2-oxo-cyclopentylmethyl ester
• 英文别名: (1-Methyl-2-oxocyclopentyl)methyl cyclopropanecarboxylate
• 化学式: C₁₁H₁₆O₃
• 分子量: 196.246
• InChiKey: JCZPJKCHLYJWIH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (2-ethoxy-1-methylcyclopent-2-en-1-yl)methanol 在 吡啶 、 硫酸 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 61.0h， 生成 (3aR,6aS,9aS)-6a-Methyl-hexahydro-1,5-dioxa-cyclopenta[d]inden-4-one 、 (4aS,7aS)-4-(2-Bromo-ethyl)-4a-hydroxy-7a-methyl-hexahydro-cyclopenta[c]pyran-3-one 、 Cyclopropanecarboxylic acid 1-methyl-2-oxo-cyclopentylmethyl ester
  参考文献：
  名称：

  Daphniphyllum Alkaloids. 16. Total Synthesis of (+)-Codaphniphylline

  摘要：

  A total synthesis of (+)-codaphniphylline (3) has been developed. The synthesis begins with Noyori asymmetric reduction of methyl 2-oxocyclopentanecarboxylate (15), which gives the trans-P-hydroxy ester 16 (93% ee). Frater-Seebach alkylation of this material with homogeranyl iodide gives hydroxy esters 18 and 19 in a ratio of 15:1. This mixture is oxidized to keto ester 29, which is converted into acetal 34. Reduction of the ester function gives primary alcohol 35, which is esterified by treatment with 2-bromo-4-chlorobutanoyl chloride. The resulting keto ester, 33, is treated with unactivated zinc dust in the presence of 2 equiv of ZnCl2 to obtain lactone ether 36, which is reduced by lithium aluminum hydride to diol 9. Serial treatment of this material with Swern oxidant, methylamine, and warm acetic acid provides the hexacyclic amino ether 10 in 63% overall yield. Reductive fragmentation to 11 results when 10 is treated with excess diisobutylaluminum hydride in hot toluene. Ring closure to the daphnane skeleton (12) occurs when the N,O-bis(phenylcarbamoyl) derivative 41 is treated with hot acetic acid, followed by KOH in methanol. Displacement of the tosyl group gives sulfide 50, which is oxidized to sulfone 13. This material is metalated and coupled with enantiomerically-pure aldehyde 46 to secure the codaphniphylline skeleton, as a mixture of four diastereomeric beta-hydroxy sulfones (51). Oxidation gives a mixture of diastereomeric beta-keto sulfones (52), which is desulfonated to obtain (+)-codaphniphylline (3). The synthesis requires 12 steps from homogeranyl iodide, the more precious starting material, and provides the enantiomerically pure alkaloid in 9% overall yield.

  DOI：

  10.1021/jo00110a013

文献信息

• Daphniphyllum Alkaloids. 16. Total Synthesis of (+)-Codaphniphylline
  作者：Clayton H. Heathcock、John C. Kath、Roger B. Ruggeri

  DOI：10.1021/jo00110a013

  日期：1995.3

  A total synthesis of (+)-codaphniphylline (3) has been developed. The synthesis begins with Noyori asymmetric reduction of methyl 2-oxocyclopentanecarboxylate (15), which gives the trans-P-hydroxy ester 16 (93% ee). Frater-Seebach alkylation of this material with homogeranyl iodide gives hydroxy esters 18 and 19 in a ratio of 15:1. This mixture is oxidized to keto ester 29, which is converted into acetal 34. Reduction of the ester function gives primary alcohol 35, which is esterified by treatment with 2-bromo-4-chlorobutanoyl chloride. The resulting keto ester, 33, is treated with unactivated zinc dust in the presence of 2 equiv of ZnCl2 to obtain lactone ether 36, which is reduced by lithium aluminum hydride to diol 9. Serial treatment of this material with Swern oxidant, methylamine, and warm acetic acid provides the hexacyclic amino ether 10 in 63% overall yield. Reductive fragmentation to 11 results when 10 is treated with excess diisobutylaluminum hydride in hot toluene. Ring closure to the daphnane skeleton (12) occurs when the N,O-bis(phenylcarbamoyl) derivative 41 is treated with hot acetic acid, followed by KOH in methanol. Displacement of the tosyl group gives sulfide 50, which is oxidized to sulfone 13. This material is metalated and coupled with enantiomerically-pure aldehyde 46 to secure the codaphniphylline skeleton, as a mixture of four diastereomeric beta-hydroxy sulfones (51). Oxidation gives a mixture of diastereomeric beta-keto sulfones (52), which is desulfonated to obtain (+)-codaphniphylline (3). The synthesis requires 12 steps from homogeranyl iodide, the more precious starting material, and provides the enantiomerically pure alkaloid in 9% overall yield.