(1S,4S,5R,6R,8R)-4,6-bis(hydroxymethyl)-8-isopropyl-8-methoxy-1-methyl-3,7-dioxabicyclo<3.3.0>octan-2-one | 171924-77-9

• 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: (1S,4S,5R,6R,8R)-4,6-bis(hydroxymethyl)-8-isopropyl-8-methoxy-1-methyl-3,7-dioxabicyclo<3.3.0>octan-2-one
• 英文别名: (1S,3aS,4R,6R,6aR)-1,6-bis(hydroxymethyl)-4-methoxy-3a-methyl-4-propan-2-yl-6,6a-dihydro-1H-furo[3,4-c]furan-3-one
• CAS: 171924-77-9
• 化学式: C₁₃H₂₂O₆
• 分子量: 274.314
• InChiKey: QQNKNOGZILPJJJ-STPAWDDFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  三甲基乙酰氯 、 (1S,4S,5R,6R,8R)-4,6-bis(hydroxymethyl)-8-isopropyl-8-methoxy-1-methyl-3,7-dioxabicyclo<3.3.0>octan-2-one 以 吡啶 为溶剂， 反应 5.0h， 以10%的产率得到2,2-Dimethyl-propionic acid (1R,3R,3aS,6S,6aR)-6-(2,2-dimethyl-propionyloxymethyl)-3-isopropyl-3-methoxy-3a-methyl-4-oxo-tetrahydro-furo[3,4-c]furan-1-ylmethyl ester
  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：

  (1S,4S,5R,6R,8R)-6-(acetoxymethyl)-8-isopropyl-8-methoxy-1-methyl-4-<(pivaloyloxy)methyl>-3,7-dioxabicyclo<3.3.0>octan-2-one 在 sodium methylate 作用下， 以 甲醇 为溶剂， 反应 9.0h， 生成 (1S,4S,5R,6R,8R)-4,6-bis(hydroxymethyl)-8-isopropyl-8-methoxy-1-methyl-3,7-dioxabicyclo<3.3.0>octan-2-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