N-formyl-beta-L-aspartyl-L-phenylalanine methyl ester | 87093-92-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: N-formyl-beta-L-aspartyl-L-phenylalanine methyl ester
• 英文别名: (2S)-2-formamido-4-[[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl]amino]-4-oxobutanoic acid
• CAS: 87093-92-3
• 化学式: C₁₅H₁₈N₂O₆
• 分子量: 322.318
• InChiKey: ZEBUKQKZQCTVEU-RYUDHWBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  122
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-formyl-beta-L-aspartyl-L-phenylalanine methyl ester 生成 N-formyl-L-beta-aspartyl-L-phenylalanine
  参考文献：
  名称：

  TSUJI, TOSHIAKI;KISHIMOTO, SHINICHI

  摘要：

  DOI：
• 作为产物：
  描述：

  (S)-(-)-2-甲酰胺琥珀酸酐 、 L-苯丙氨酸甲酯 生成 N-formyl-beta-L-aspartyl-L-phenylalanine methyl ester
  参考文献：
  名称：

  YUKAWA, TOSHIHIDE;KAWASAKI, HARUO;NAKAMURA, MASAO;YAMASHITA, TAKASHI;TSUJ+

  摘要：

  DOI：

文献信息

• Preparation of N-protected .alpha.-L-aspartyl-L-phenylalanine methyl
  申请人：Mitsui Toatsu Chemicals, Inc.

  公开号：US05302743A1

  公开（公告）日：1994-04-12

  Disclosed is an improved process for the preparation of an N-protected .alpha.-L-aspartyl-L-phenylalanine methyl ester from an N-protected L-aspartic anhydride and L-phenylalanine methyl ester, the improvement which comprises employing the L-phenylalanine methyl ester in the form of a mineral acid salt thereof and conducting the reaction either (a) in an organic solvent and in the presence of a salt of an organic carboxylic acid, or (b) in an organic solvent comprising an organic carboxylic acid and in the presence of at least one member of the group consisting of an alkali metal or an alkaline earth metal inorganic base, an ammonium alkali metal or alkaline earth metal salt of an organic carboxylic acid and ammonium carbonate. The starting N-protected aspartic anhydride, e.g., N-benzyloxycarbonyl-L-aspartic anhydride, can be produced by the reaction of N-protected aspartic acid with phosgene. When the N-protecting group sibenzyloxycarbonyl and the solvent is acetic acid, the desired product can be isolated from the reaction mixture in crystalline form in high purity by adding water thereto.

  本发明公开了一种改进的方法，用于从N-保护的L-天冬氨酸酐和L-苯丙氨酸甲酯制备N-保护的α-L-天冬氨酸基-L-苯丙氨酸甲酯。改进的方法包括采用L-苯丙氨酸甲酯的矿酸盐形式，并在有机溶剂中以及有机羧酸盐的存在下进行反应，或者在有机溶剂中含有有机羧酸盐并在至少一种由碱金属或碱土金属无机碱、有机羧酸的铵碱金属或碱土金属盐和碳酸铵组成的群体成员的存在下进行反应。起始的N-保护天冬氨酸酐，例如N-苄氧羰基-L-天冬氨酸酐，可以通过N-保护天冬氨酸与光气反应来制得。当N-保护基为苄氧羰基且溶剂为乙酸时，可以通过加水从反应混合物中结晶形式高纯度地分离所需产品。
• Process for removing an n-formyl group
  申请人：AJINOMOTO CO., INC.

  公开号：EP0058063A1

  公开（公告）日：1982-08-18

  An L-aspartyl-L-phenylalanine lower alkyl ester of which the amino group of the aspartyl residue is protected with a formyl group can be deformylated under selected conditions, i.e. in a strong acid, having a specific normality range at a specific elevated temperature range, and the splitting of the formyl group from the aspartyl moiety amino group can be effected selectively and efficiently in a short time (e.g. as short as 15 seconds to 60 minutes), while the splitting of the ester bond or the peptide bond is suppressed. The deformylation is useful in the production of a-L-aspartyl-L-phenylalanine methyl ester, a dipeptide sweetener.

  天冬氨酰残基的氨基被甲酰基保护的 L-天冬氨酰-L-苯丙氨酸低级烷基酯可在选定的条件下，即在具有特定常态范围的强酸中，在特定的升高温度范围内，进行脱甲酰反应。甲酰基与天冬氨酰残基氨基的分离可在短时间内（例如短至 15 秒至 60 分钟）选择性地有效进行，同时酯键或肽键的分离受到抑制。这种变形作用可用于生产一种二肽甜味剂--L-天冬氨酰-L-苯丙氨酸甲酯。
• Process for preparing alpha-L-aspartyl-L-phenylalanine methyl ester
  申请人：DE-BI DERIVATI BIOLOGICI INTERNATIONAL S.p.A.

  公开号：EP0132856A2

  公开（公告）日：1985-02-13

  A process for preparing a-L-aspartyl-L-phenylalanine methyl ester consisting of: - bringing N-formyl-L-aspartic anhydride and L-phenylalanine methyl ester, in a molar ratio equal or approximately equal to 1:1, into contact with a solid cation exchange resin having free sulphonic, phosphonic or carboxylic acid groups, the ratio of the acid equivalents of said resin acid groups to the number of moles of the one or other reagent being equal to or lessthan about 1:1, and operating in the liquid phase in an inert organic solvent at a temperature of about 40°C or less, until a mixture of N-formyl-a-L-aspartyl-L-phenylalanine methyl ester and N-formyl-β-L-aspartyl-L-phenylalanine methyl ester forms in which the a isomer prevails over the p isomer; - deformylating said N-formyl-a-L- aspartyl-L-phenylalanine methyl ester and N-formyl -β-L- aspartyl -L-phenylalanine methyl ester; and - separating and recovering the a-L- aspartyl -L-phenylalanine methyl esterfrom said deformylated products.

  一种制备 L-天冬氨酰-L-苯丙氨酸甲酯的工艺，包括 - 将摩尔比等于或近似等于 1:1 的 N-甲酰基-L-天冬氨酸酐和 L-苯丙氨酸甲酯与具有游离磺酸基、膦酸基或羧酸基的固态阳离子交换树脂接触，所述树脂酸基的酸当量与一种或其他试剂的摩尔数之比等于或小于约 1：1，并在温度约为 40°C 或更低的惰性有机溶剂中进行液相操作，直至形成 N-甲酰基-a-L-天冬氨酰-L-苯丙氨酸甲酯和 N-甲酰基-β-L-天冬氨酰-L-苯丙氨酸甲酯的混合物，其中 a 异构体优于 p 异构体； - 使所述 N-甲酰基-a-L-天冬氨酰-L-苯丙氨酸甲酯和 N-甲酰基-β-L-天冬氨酰-L-苯丙氨酸甲酯变形；以及 - 从所述变形产物中分离并回收 a-L-天冬氨酰-L-苯丙氨酸甲酯。
• Synthesis and recovery of aspartame involving enzymatic deformylation step
  申请人：Holland Sweetener Company V.O.F.

  公开号：EP1013663A1

  公开（公告）日：2000-06-28

  The invention relates to the synthesis of aspartame involving enzymatic deformylation of an N-formyl-α-L-aspartyl-L-phenylalanine compound by treatment with an enzyme having formylmethionyl peptide deformylase activity and having as a co-factor group 5 to 11 bivalent metal ions. The invention also relates to selective preparation and recovery of aspartame from a mixture of N-formyl-α- and β-L-aspartyl-L-phenylalanine compounds by treatment with such enzyme. And finally, the invention relates to one-pot enzymatic synthesis of aspartame from N-formyl-L-aspartic acid and L- or D,L-phenylalanine methyl ester involving an enzymatic deformylation reaction simultaneously with an enzymatic coupling reaction, as well as to one-pot di- or oligopeptide synthesis by simultaneous enzymatic coupling and deformylation reactions in general.

  本发明涉及天冬酰胺的合成，包括用具有甲酰基蛋氨酰肽变形酶活性的酶处理 N-甲酰基-α-L-天冬氨酰-L-苯丙氨酸化合物，并用 5 至 11 个二价金属离子作为辅助因子基团，使其酶促变形。本发明还涉及用这种酶处理从 N-甲酰基-α-和 β-L-天冬氨酰-L-苯丙氨酸化合物混合物中选择性制备和回收阿斯巴甜。最后，本发明涉及由 N-甲酰基-L-天冬氨酸和 L-或 D,L-苯丙氨酸甲酯通过酶促脱甲酰反应和酶促偶联反应一次酶法合成天冬酰胺，以及通过同时进行酶促偶联反应和脱甲酰反应一次酶法合成二肽或寡肽。
• Kuhl, Peter; Schaaf, Regina, Zeitschrift fur Chemie, 1990, vol. 30, # 6, p. 212 - 213
  作者：Kuhl, Peter、Schaaf, Regina

  DOI：——

  日期：——