(1S,6S,7S,8R,8aR)-1-Acetoxy-6,7-(isopropylidenedioxy)-8-(methoxymethoxy)indolizidine | 145625-46-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚里西啶
• 英文名称: (1S,6S,7S,8R,8aR)-1-Acetoxy-6,7-(isopropylidenedioxy)-8-(methoxymethoxy)indolizidine
• 英文别名: [(3aS,8S,8aR,9R,9aR)-9-(methoxymethoxy)-2,2-dimethyl-3a,4,6,7,8,8a,9,9a-octahydro-[1,3]dioxolo[4,5-f]indolizin-8-yl] acetate
• CAS: 145625-46-3
• 化学式: C₁₅H₂₅NO₆
• 分子量: 315.367
• InChiKey: SBZRSTFPFLCOLN-ODXJTPSBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  66.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1S,6S,7S,8R,8aR)-1-Acetoxy-6,7-(isopropylidenedioxy)-8-(methoxymethoxy)indolizidine 在 盐酸 作用下， 反应 0.5h， 以69%的产率得到(+)-1-O-Acetylcastanospermine
  参考文献：
  名称：

  Total syntheses of (+)-castanospermine and (+)-1-epicastanospermine and their 1-O-acyl derivatives from a common chiral building block

  摘要：

  Stereoselective total syntheses of (+)-castanospermine (1) and (+)-1-epicastanospermine (2) and their 1-O-acyl derivatives 3-5 have been achieved via a noncarbohydrate-based approach utilizing allylic alcohol 9 as a common chiral building block. Epoxide 10, prepared from 9, underwent regioand stereoselective ring opening with Et2AlN(CH2Ph)2 to give amino alcohol 11, which was converted to aldehyde 15 in four steps. The aldol reaction of 15 with lithio ethyl acetate was predominantly anti selective and generated alpha-hydroxy ester 16 by a nonchelate Felkin-Anh pathway. Compound 16 was transformed into (+)-1-epicastanospermine (2) and its 1-O-acetyl and 1-O-butyryl derivatives (4 and 5) via the lactam intermediate 21. Alternatively, alpha-hydroxy ester 16 was converted to (+)-castanospermine (1) and its 1-O-acetyl derivative (3); these syntheses were achieved via reaction sequences involving the inversion of the C-3 configuration by the Mitsunobu process and 2-fold tandem cyclizations to form the indolizidine skeleton. The results of preliminary biological testing of compounds 2-5 for anti-HIV-1 activity in whole cells are presented.

  DOI：

  10.1021/jo00053a015
• 作为产物：
  描述：

  (2S,3R,4S,5S)-6-<(tert-butyldimethylsilyl)oxy>-2,3-epoxy-4,5-(isopropylidenedioxy)hexan-1-ol 在 palladium dihydroxide 、 palladium on activated charcoal 咪唑 、 lithium aluminium tetrahydride 、 草酰氯 、 四溴化碳 、 四丁基氟化铵 、 氢气 、 三乙基铝 、 sodium carbonate 、 二甲基亚砜 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 、 锌 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 氯仿 、 水 、 N,N-二甲基甲酰胺 、 苯 为溶剂， -80.0~25.0 ℃ 、101.33 kPa 条件下， 反应 67.0h， 生成 (1S,6S,7S,8R,8aR)-1-Acetoxy-6,7-(isopropylidenedioxy)-8-(methoxymethoxy)indolizidine
  参考文献：
  名称：

  Total syntheses of (+)-castanospermine and (+)-1-epicastanospermine and their 1-O-acyl derivatives from a common chiral building block

  摘要：

  Stereoselective total syntheses of (+)-castanospermine (1) and (+)-1-epicastanospermine (2) and their 1-O-acyl derivatives 3-5 have been achieved via a noncarbohydrate-based approach utilizing allylic alcohol 9 as a common chiral building block. Epoxide 10, prepared from 9, underwent regioand stereoselective ring opening with Et2AlN(CH2Ph)2 to give amino alcohol 11, which was converted to aldehyde 15 in four steps. The aldol reaction of 15 with lithio ethyl acetate was predominantly anti selective and generated alpha-hydroxy ester 16 by a nonchelate Felkin-Anh pathway. Compound 16 was transformed into (+)-1-epicastanospermine (2) and its 1-O-acetyl and 1-O-butyryl derivatives (4 and 5) via the lactam intermediate 21. Alternatively, alpha-hydroxy ester 16 was converted to (+)-castanospermine (1) and its 1-O-acetyl derivative (3); these syntheses were achieved via reaction sequences involving the inversion of the C-3 configuration by the Mitsunobu process and 2-fold tandem cyclizations to form the indolizidine skeleton. The results of preliminary biological testing of compounds 2-5 for anti-HIV-1 activity in whole cells are presented.

  DOI：

  10.1021/jo00053a015

文献信息

• Total syntheses of (+)-castanospermine and (+)-1-epicastanospermine and their 1-O-acyl derivatives from a common chiral building block
  作者：Hiroji Ina、Chihiro Kibayashi

  DOI：10.1021/jo00053a015

  日期：1993.1

  Stereoselective total syntheses of (+)-castanospermine (1) and (+)-1-epicastanospermine (2) and their 1-O-acyl derivatives 3-5 have been achieved via a noncarbohydrate-based approach utilizing allylic alcohol 9 as a common chiral building block. Epoxide 10, prepared from 9, underwent regioand stereoselective ring opening with Et2AlN(CH2Ph)2 to give amino alcohol 11, which was converted to aldehyde 15 in four steps. The aldol reaction of 15 with lithio ethyl acetate was predominantly anti selective and generated alpha-hydroxy ester 16 by a nonchelate Felkin-Anh pathway. Compound 16 was transformed into (+)-1-epicastanospermine (2) and its 1-O-acetyl and 1-O-butyryl derivatives (4 and 5) via the lactam intermediate 21. Alternatively, alpha-hydroxy ester 16 was converted to (+)-castanospermine (1) and its 1-O-acetyl derivative (3); these syntheses were achieved via reaction sequences involving the inversion of the C-3 configuration by the Mitsunobu process and 2-fold tandem cyclizations to form the indolizidine skeleton. The results of preliminary biological testing of compounds 2-5 for anti-HIV-1 activity in whole cells are presented.