Boc-Ama(OBn)-OH | 119881-03-7

• 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: Boc-Ama(OBn)-OH
• 英文别名: 1-(Phenylmethyl) 2-[[(1,1-dimethylethoxy)carbonyl]amino]propanedioate；2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxo-3-phenylmethoxypropanoic acid
• CAS: 119881-03-7
• 化学式: C₁₅H₁₉NO₆
• 分子量: 309.319
• InChiKey: ASBKUBVQAHXKPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Boc-Ama(OBn)-OH 在 N-甲基吗啉 、 盐酸 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 58.17h， 生成 H-Ala-Leu-Ama(OMe)-OBn hydrochloride
  参考文献：
  名称：

  C-Alkylation of Peptides Containing Aminomalonate and (Amino)(cyano)acetate Residues

  摘要：

  N-Acetyl-, N-[(tert-butoxy)carbonyl](Boc)-, and N-[(benzyloxy)carbonyl](Z)-protected tri-, penta-, and heptapeptide methyl esters, 1-8, with a central aminomalonate (Ama) (allyl, methyl, benzyl, or tert-butyl) or (amino)(cyano)acetate (Aca) residue have been prepared by conventional techniques (Schemes 4-6). The new peptides with acidic backbone-bound CH groups can be C-alkylated with primary alkyl, allyl, and benzyl halides, under mildly basic conditions (1 equiv. MeONa or t-BuOK in THF); also, they can be added to Michael accepters such as acrylates, acrylonitrile, methyl vinyl ketone, or nitrostyrene (catalytic amounts of alkoxide bases in THF) (Schemes 7-16). In most cases, the products, 48-100, are formed in excellent yields (average of 77%); one of the epimeric products prevails (2:1 to > 20:1), and the epimers have been separated, isolated in pure form, and fully characterized (without configurational assignments); addition of the co-solvent 3,4,5,6-tetrahydro-1,3-dimethylpyrimidin-2(1H)-one (DMPU) or of LiBr may improve or even reverse the ratio of epimeric products formed; the heptapeptide derivative 8 had to be solubilized for alkylations in THF by the addition of 30 equiv. of LiBr. Cleavage of the Ama groups (benzyl with H-2/Pd-C, t-Bu with HCl/Et2O) gave carboxylate derivatives which are actually peptides containing the alkylated aminomalonic acid, the lower homolog of aspartic acid, as residue in the central position. These acids are quite resistant to decarboxylation which had to be achieved by heating at reflux in THF in the presence of 2 equiv. of LiBr and of catalytic amounts of pyridine (Schemes 17 and 18). A one-step removal of the allyl aminomalonate group is possible with Pd/PPh3/formate (Scheme 19). The resulting peptides, 101-115, were formed as separable I: 1 mixtures of two epimers. The CN group of the alkylated Aca residue can be removed reductively (Na/NH3; Scheme 20). The value of the new method is compared with that of existing methods of peptide-backbone modification.

  DOI：

  10.1002/(sici)1522-2675(19981007)81:10<1845::aid-hlca1845>3.0.co;2-l
• 作为产物：
  描述：

  二氧化碳 、 叔丁氧羰基氨基-乙酸苄酯 在 四甲基乙二胺 、 lithium diisopropyl amide 作用下， 生成 Boc-Ama(OBn)-OH
  参考文献：
  名称：

  Bossler, Hans G.; Waldmeier, Pius; Seebach, Dieter, Angewandte Chemie, 1994, vol. 106, # 4, p. 455 - 456

  摘要：

  DOI：

文献信息

• New Synthesis for the Monobactam Antibiotic—<b>LYS228</b>
  作者：Zhongbo Fei、Quanbing Wu、Lei Li、Qun Jiang、Bin Li、Like Chen、Hao Wang、Bin Wu、Xianwen Wang、Feng Gao、Wenlong Qiu、Jing Guo、Chi Ming Cheung

  DOI：10.1021/acs.joc.9b01916

  日期：2020.6.5

  A new synthesis of LYS228, fitting for further process development for commercial manufacture, is described. The key features of this synthesis include development of new protocols for acylation reactions, application of an asymmetric hydrogenation via dynamic kinetic resolution, and a late-stage ring closure to form β-lactam 1.

  描述了LYS228的新合成方法，适用于商业生产的进一步工艺开发。该合成的关键特征包括开发新的酰化反应方案，通过动态动力学拆分应用不对称氢化以及后期闭环形成β-内酰胺1。
• [EN] PROCESS FOR PREPARING 1 -(((Z)-(1 -(2-AMINOTHIAZOL-4-YL)-2-OXO-2-(((3S,4R)-2-OXO-4-((2-OXOOXAZOLIDIN-3-Y L)METHYL)-1 -SULFOAZETIDIN-3- YL)AMINO)ETHYLIDENE)AMINO)OXY)CYCLOPROPANE CARBOXYLIC ACID<br/>[FR] PROCESSUS CHIMIQUE DE PRÉPARATION D'ANTIBIOTIQUE MONOBACTAME ET DE SES INTERMÉDIAIRES
  申请人：NOVARTIS AG

  公开号：WO2019026004A3

  公开（公告）日：2019-03-14
• HISTONE DEACETYLASE INHIBITORS AND COMPOSITIONS AND METHODS OF USE THEREOF
  申请人：CHDI Foundation, Inc.

  公开号：US20190202795A1

  公开（公告）日：2019-07-04

  Provided are certain histone deacetylase (HDAC) inhibitors of Formula I, compositions thereof, and methods of their use.
• CHEMICAL PROCESS FOR MANUFACTURING MONOBACTAM ANTIBIOTIC AND INTERMEDIATES THEREOF
  申请人：Novartis AG

  公开号：US20200239461A1

  公开（公告）日：2020-07-30

  The present invention provides a process of synthesizing 1-(((Z)-(1-(2-aminothiazol-4-yl)-2-oxo-2-(((3S,4R)-2-oxo-4-((2-oxooxazolidin-3-yl)methyl)-1-sulfoazetidin-3 yl)amino)ethylidene)amino)oxy)cyclopropanecarboxylic acid (referred to herein as Compound X), or a salt thereof, or a solvate including hydrate thereof, and/or intermediates thereof, and the use of intermediates for preparing Compound X. In particular, the process relates to the preparation of Compound X using dynamic kinetic resolution (DKR) and asymmetric catalytic reduction, thereby providing an improved route to 1-(((Z)-(1-(2-aminothiazol-4-yl)-2-oxo-2-(((3S,4R)-2-oxo-4-((2-oxooxazolidin-3-yl)methyl)-1-sulfoazetidin-3 yl)amino)ethylidene)amino)oxy)cyclopropanecarboxylic acid (Compound X) and compositions containing said compound, including the arginine salt, sodium salt and hydrated solid forms of Compound X.