(3S,3aR,4S,6R,6aS)-4-((R)-5-Ethyl-2-methyl-3-oxo-2,3-dihydro-furan-2-ylmethyl)-3-hydroxymethyl-6-isopropyl-6-methoxy-6a-methyl-tetrahydro-furo[3,4-c]furan-1-one | 171924-76-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃类
• 英文名称: (3S,3aR,4S,6R,6aS)-4-((R)-5-Ethyl-2-methyl-3-oxo-2,3-dihydro-furan-2-ylmethyl)-3-hydroxymethyl-6-isopropyl-6-methoxy-6a-methyl-tetrahydro-furo[3,4-c]furan-1-one
• 英文别名: (1S,3R,3aS,6S,6aR)-1-[[(2R)-5-ethyl-2-methyl-3-oxofuran-2-yl]methyl]-6-(hydroxymethyl)-3-methoxy-3a-methyl-3-propan-2-yl-6,6a-dihydro-1H-furo[3,4-c]furan-4-one
• CAS: 171924-76-8
• 化学式: C₂₀H₃₀O₇
• 分子量: 382.454
• InChiKey: HGKQFOOOHGCOHB-PNYFVIERSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  91.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3S,3aR,4S,6R,6aS)-4-((R)-5-Ethyl-2-methyl-3-oxo-2,3-dihydro-furan-2-ylmethyl)-3-hydroxymethyl-6-isopropyl-6-methoxy-6a-methyl-tetrahydro-furo[3,4-c]furan-1-one 在 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (1S,3aS,4R,6S,6aR)-6-((R)-5-Ethyl-2-methyl-3-oxo-2,3-dihydro-furan-2-ylmethyl)-4-isopropyl-4-methoxy-3a-methyl-3-oxo-tetrahydro-furo[3,4-c]furan-1-carbaldehyde
  参考文献：
  名称：

  Novel Total Synthesis of (+)-Eremantholide A

  摘要：

  Stereoselective total synthesis of (+)-eremantholide A (1), a cytotoxic furanoheliangolide sesquiterpene, was accomplished in an enantiospecific fashion. The total synthesis featured the following three key synthetic strategies. (1) Intramolecular cyclization of carbon-radicals derived from xanthates 19a or 19b proceeded regio- and stereoselectively in an exclusive 5-exo-dig mode to provide bicyclic lactones 20a or 20b. Further functional group manipulations of 20a and 20b efficiently afforded a highly substituted 3,7-dioxabicyclo[3.3.0]octan-2-one derivative 34, which served as a synthetic equivalent to the A/B ring system in 1. (2) Alkylation of the enolate of 3(2H)-furanone 36 with triflate 35 was thoroughly investigated to maximize formation of the C-alkylated diastereomers, either 10R-isomer 37 or 10S-isomer 38. It was found that choice of the base, solvent, and/or additive was critical to the diastereoselectivity. Furthermore, the 10R-isomer 50 was also prepared in increased yield and improved diastereoselectivity by coupling 36 with A/B ring equivalent 49. (3) In a later stage of the total synthesis, construction of the strained 11-oxabicyclo-[6.2.1]undeca-2,10-dien-9-one system (the C/D ring) was accomplished by means of an intramolecular vinylogous aldol reaction of aldehyde 52, prepared from 10R-isomer 40, followed by base-catalyzed beta-elimination of the corresponding mesylates 54. On the other hand, by employing analogous reaction conditions, the 10S-isomer 56 was transformed into unnatural (-)-10-epi-eremantholide A (61).

  DOI：

  10.1021/jo00130a017
• 作为产物：
  描述：

  (1R,2S,5S,6S,7R)-8-hydroxy-1-isopropyl-2-methyl-5-<(pivaloyloxy)methyl>-4,9,10-trioxatricyclo<5.2.1.0^2,6>decan-3-one 在 sodium tetrahydroborate 、 18-冠醚-6 、 sodium methylate 、 4-甲基苯磺酸吡啶 、 双(三甲基硅烷基)氨基钾 、 三乙胺 作用下， 以 吡啶 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 11.25h， 生成 (3S,3aR,4S,6R,6aS)-4-((R)-5-Ethyl-2-methyl-3-oxo-2,3-dihydro-furan-2-ylmethyl)-3-hydroxymethyl-6-isopropyl-6-methoxy-6a-methyl-tetrahydro-furo[3,4-c]furan-1-one
  参考文献：
  名称：

  Novel Total Synthesis of (+)-Eremantholide A

  摘要：

  Stereoselective total synthesis of (+)-eremantholide A (1), a cytotoxic furanoheliangolide sesquiterpene, was accomplished in an enantiospecific fashion. The total synthesis featured the following three key synthetic strategies. (1) Intramolecular cyclization of carbon-radicals derived from xanthates 19a or 19b proceeded regio- and stereoselectively in an exclusive 5-exo-dig mode to provide bicyclic lactones 20a or 20b. Further functional group manipulations of 20a and 20b efficiently afforded a highly substituted 3,7-dioxabicyclo[3.3.0]octan-2-one derivative 34, which served as a synthetic equivalent to the A/B ring system in 1. (2) Alkylation of the enolate of 3(2H)-furanone 36 with triflate 35 was thoroughly investigated to maximize formation of the C-alkylated diastereomers, either 10R-isomer 37 or 10S-isomer 38. It was found that choice of the base, solvent, and/or additive was critical to the diastereoselectivity. Furthermore, the 10R-isomer 50 was also prepared in increased yield and improved diastereoselectivity by coupling 36 with A/B ring equivalent 49. (3) In a later stage of the total synthesis, construction of the strained 11-oxabicyclo-[6.2.1]undeca-2,10-dien-9-one system (the C/D ring) was accomplished by means of an intramolecular vinylogous aldol reaction of aldehyde 52, prepared from 10R-isomer 40, followed by base-catalyzed beta-elimination of the corresponding mesylates 54. On the other hand, by employing analogous reaction conditions, the 10S-isomer 56 was transformed into unnatural (-)-10-epi-eremantholide A (61).

  DOI：

  10.1021/jo00130a017

文献信息

• A total synthesis of (+)-eremantholide A
  作者：Ken-ichi Takao、Hiroshi Ochiai、Takahiko Hashizuka、Hirokazu Koshimura、Kin-ichi Tadano、Seiichiro Ogawa

  DOI：10.1016/0040-4039(95)00066-l

  日期：1995.2

  Stereoselective and enantiospecific total synthesis of (+)-eremantholide A (1) is described. The present total synthesis features 1) regio- and stereoselective radical carbocyclization of D-glurose-derived gamma-lactone 7, and 2) a nine-membered ring formation by the coupling reaction of bicyclic triflate 18 and known furanone 19 followed by a vinylogous aldol reaction.
• Novel Total Synthesis of (+)-Eremantholide A
  作者：Ken-ichi Takao、Hiroshi Ochiai、Ken-ichi Yoshida、Takahiko Hashizuka、Hirokazu Koshimura、Kin-ichi Tadano、Seiichiro Ogawa

  DOI：10.1021/jo00130a017

  日期：1995.12

  Stereoselective total synthesis of (+)-eremantholide A (1), a cytotoxic furanoheliangolide sesquiterpene, was accomplished in an enantiospecific fashion. The total synthesis featured the following three key synthetic strategies. (1) Intramolecular cyclization of carbon-radicals derived from xanthates 19a or 19b proceeded regio- and stereoselectively in an exclusive 5-exo-dig mode to provide bicyclic lactones 20a or 20b. Further functional group manipulations of 20a and 20b efficiently afforded a highly substituted 3,7-dioxabicyclo[3.3.0]octan-2-one derivative 34, which served as a synthetic equivalent to the A/B ring system in 1. (2) Alkylation of the enolate of 3(2H)-furanone 36 with triflate 35 was thoroughly investigated to maximize formation of the C-alkylated diastereomers, either 10R-isomer 37 or 10S-isomer 38. It was found that choice of the base, solvent, and/or additive was critical to the diastereoselectivity. Furthermore, the 10R-isomer 50 was also prepared in increased yield and improved diastereoselectivity by coupling 36 with A/B ring equivalent 49. (3) In a later stage of the total synthesis, construction of the strained 11-oxabicyclo-[6.2.1]undeca-2,10-dien-9-one system (the C/D ring) was accomplished by means of an intramolecular vinylogous aldol reaction of aldehyde 52, prepared from 10R-isomer 40, followed by base-catalyzed beta-elimination of the corresponding mesylates 54. On the other hand, by employing analogous reaction conditions, the 10S-isomer 56 was transformed into unnatural (-)-10-epi-eremantholide A (61).