(2S,3R)-2-Ethyl-3-(methoxycarbonyl)-4-(1-methylimidazol-5-yl)-butyric acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (2S,3R)-2-Ethyl-3-(methoxycarbonyl)-4-(1-methylimidazol-5-yl)-butyric acid
• 英文别名: (2S,3R)-2-ethyl-4-methoxy-3-[(3-methylimidazol-4-yl)methyl]-4-oxobutanoic acid
• 化学式: C₁₂H₁₈N₂O₄
• 分子量: 254.286
• InChiKey: NTEDRYPRMHZGQB-VHSXEESVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  81.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3R)-2-Ethyl-3-(methoxycarbonyl)-4-(1-methylimidazol-5-yl)-butyric acid 在 盐酸 、 sodium tetrahydroborate 作用下， 生成 盐酸毛果芸香碱
  参考文献：
  名称：

  An effective chirospecific synthesis of (+)-pilocarpine from L-aspartic acid

  摘要：

  A short and efficient synthesis of (+)-pilocarpine (1) has been accomplished in 10 steps and 51 % overall yield from L-aspartic acid. The synthesis features a diastereoselective alkylation of a protected aspartic acid diester derivative and a selective hydrolysis of the alpha-methyl ester to give the corresponding amino acid. Subsequent replacement of the amino group with bromo, esterification, and a modified Reformatsky reaction with 1-methylimidazole-5-carboxaldehyde (8) afforded imidazole-substituted lactone 28. Details concerning this novel lactone synthesis are also described. Finally, hydrogenolysis of the lactone carbon-oxygen bond and selective reduction of the resulting monoester afforded pure (+)-pilocarpine (1).

  DOI：

  10.1021/jo00057a031
• 作为产物：
  描述：

  methyl (3S,4S)-4-ethyl-2-(3-methylimidazol-4-yl)-5-oxooxolane-3-carboxylate 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 以84.7 g的产率得到(2S,3R)-2-Ethyl-3-(methoxycarbonyl)-4-(1-methylimidazol-5-yl)-butyric acid
  参考文献：
  名称：

  CN116199607

  摘要：

  公开号：

文献信息

• SYNTHESIS OF OPTICALLY ACTIVE LACTONES FROM L-ASPARTIC ACID AND INTERMEDIATES THEREOF
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：EP0643710A1

  公开（公告）日：1995-03-22
• US5322942A
  申请人：——

  公开号：US5322942A

  公开（公告）日：1994-06-21
• [EN] SYNTHESIS OF OPTICALLY ACTIVE LACTONES FROM L-ASPARTIC ACID AND INTERMEDIATES THEREOF
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：WO1992021675A1

  公开（公告）日：1992-12-10

  (EN) Optically active lactones are described, such as an intermediate lactone having formula (VIa) where R and R2 are each independently alkyl with 1 to 6 carbon atoms, cycloalkyl with 6 to 10 carbon atoms, aryl with 6 to 10 carbon atoms, or arylalkyl with 7 to 19 carbon atoms, R4 is H or C1-6¿ alkyl, and Ar is a homo- or heteroaromatic ring with 5 or 6 ring atoms being optionally substituted by C¿1-6 alkyl or alkoxy groups, halogen atoms, cyano or nitro groups. Such optically active, intermediate lactones are prepared from L-aspartic acid, and can be readily converted to (+)-pilocarpine and its analogues by hydrolysis, reduction, and hydrogenation, such as to an optically active lactone having formula (VIII) which is (+)-pilocarpine when R is ethyl, R4 is H, and Ar is 1-methylimidazol-5-yl.(FR) Lactones optiquement actives, telles qu'une lactone intermédiaire de la formule (VIa) dans laquelle R et R2 sont chacun indépendamment un alkyle comprenant 1 à 6 atomes de carbone, un cycloalkyle comprenant 6 à 10 atomes de carbone, un aryle comprenant 6 à 10 atomes de carbone ou un arylalkyle comprenant 7 à 19 atomes de carbone, R4 est H ou C1-6 alkyle, et Ar est un anneau homo ou hétéroaromatique à 5 ou 6 atomes de cycle pouvant éventuellement être substitués par des groupes C1-6 alkyle ou alkoxy, des atomes halogène, des groupes cyano ou nitro. De telles lactones intermédiaires optiquement actives sont élaborées à partir de l'acide L-aspartique et peuvent être immédiatement converties en (+)-pilocarpine et ses analogues par hydrolyse, réduction et hydrogénation, par exemple en une lactone optiquement active de la formule (VIII) qui est (+)-pilocarpine quand R est un éthyle, R4 est H et Ar est 1-méthylimidazole-5-yle.