3(S)-ethyl-L-aspartic acid hydrobromide 4-methyl 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: 3(S)-ethyl-L-aspartic acid hydrobromide 4-methyl ester
• 英文别名: (2S, 3S)-2-Amino-3-(methoxycarbonyl)pentanoic acid hydrobromide；(2S,3S)-2-amino-3-methoxycarbonylpentanoic acid;hydrobromide
• 化学式: BrH*C₇H₁₃NO₄
• 分子量: 256.096
• InChiKey: KDEWXGPGFCJZSN-FHAQVOQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.18
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  89.6
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3(S)-ethyl-L-aspartic acid hydrobromide 4-methyl ester 在 palladium on activated charcoal 盐酸 、 sodium tetrahydroborate 、 草酰氯 、 硫酸 、 氢溴酸 、 银 、 ammonium formate 、 氯化二乙基铝 、 N,N-二甲基甲酰胺 、 potassium bromide 、 copper(I) bromide 、 锌 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 65.83h， 生成 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：

  (2S,3S)-dimethyl 2-N-(9-phenylfluorenyl)-3-ethyl-L-aspartate 生成 3(S)-ethyl-L-aspartic acid hydrobromide 4-methyl ester
  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

文献信息

• Synthesis of optically active lactones from L-aspartic acid and
  申请人：Regents of the University of California

  公开号：US05322942A1

  公开（公告）日：1994-06-21

  Optically active lactones are described, such as an intermediate lactone having the formula ##STR1## where R and R.sup.2 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, R.sup.4 is H or C.sub.1-6 alkyl, and Ar is a homo- or heteroaromatic ring with 5 or 6 ring atoms being optionally substituted by C.sub.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 the formula ##STR2## which is (+)-pilocarpine when R is ethyl, R.sup.4 is H, and Ar is 1-methylimidazol-5-yl.

  本文描述了光学活性内酯，例如具有以下式子的中间内酯：##STR1## 其中R和R.sup.2各自独立地为1至6个碳原子的烷基，6至10个碳原子的环烷基，6至10个碳原子的芳基或7至19个碳原子的芳基烷基，R.sup.4为H或C.sub.1-6烷基，Ar为同源或异源芳香环，其中5或6个环原子可选择地被C.sub.1-6烷基或烷氧基，卤素原子，氰基或硝基取代。这些光学活性的中间内酯是从L-天冬氨酸制备的，并且可以通过水解，还原和加氢轻松转化为(+)-吡拉卡林及其类似物，例如具有以下式子的光学活性内酯：##STR2## 当R为乙基，R.sup.4为H，Ar为1-甲基咪唑-5-基时，其为(+)-吡拉卡林。
• 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.