(R)-3-benzyloxycarbonylamino-2-hydroxypropionic acid | 42491-80-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-3-benzyloxycarbonylamino-2-hydroxypropionic acid
• 英文别名: R-(β-benzyloxycarbonylamino)-α-hydroxypropionic acid；(2R)-3-{[(benzyloxy)carbonyl]amino}-2-hydroxypropanoic acid；N-<(Benzyloxy)carbonyl>-(R)-isoserin；Propanoic acid, 2-hydroxy-3-[[(phenylmethoxy)carbonyl]amino]-, (2R)-；(2R)-2-hydroxy-3-(phenylmethoxycarbonylamino)propanoic acid
• CAS: 42491-80-5
• 化学式: C₁₁H₁₃NO₅
• 分子量: 239.228
• InChiKey: GMWQKAHYINBSDJ-SECBINFHSA-N

物化性质

• 熔点：
  131-132 °C
• 沸点：
  494.5±45.0 °C(Predicted)
• 密度：
  1.354±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-3-benzyloxycarbonylamino-2-hydroxypropionic acid 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 17.0h， 以92%的产率得到(R)-异丝氨酸
  参考文献：
  名称：

  Novel Glucagon Receptor Antagonists with Improved Selectivity over the Glucose-Dependent Insulinotropic Polypeptide Receptor

  摘要：

  Optimization of a new series of small molecule human glucagon receptor (hGluR) antagonists is described. In the process of optimizing glucagon receptor antagonists, we counter-screened against the closeli related human gastric inhibitory polypeptide receptor (hGIPR), and through structure activity analysis, we obtained compounds with low nanomolar affinities toward the hGluR, which were selective against the hGIPR and the human glucagon-like peptide-1 receptor (hGLP-1R). In the best cases, we obtained a >50 fold selectivity for the hGluR over the hGIPR and a > 1000 fold selectivity over the hGLP-1R. A potent and selective glucagon receptor antagonist was demonstrated to inhibit glucagon-induced glycogenolysis in primary rat hepatocytes as well as to lower glucagon-induced hyperolycemia in Sprague-Dawley rats. Furthermore. the compound was shown to lower blood glucose in the ob/ob mouse after oral dosing.

  DOI：

  10.1021/jm7015599
• 作为产物：
  描述：

  (R)-(2,2-dimethyl-5-oxo-[1,3]dioxalan-4-ylmethyl)carbamic acid benzyl ester 在 盐酸 、 水 作用下， 以 乙腈 为溶剂， 反应 3.0h， 以87%的产率得到(R)-3-benzyloxycarbonylamino-2-hydroxypropionic acid
  参考文献：
  名称：

  Novel Glucagon Receptor Antagonists with Improved Selectivity over the Glucose-Dependent Insulinotropic Polypeptide Receptor

  摘要：

  Optimization of a new series of small molecule human glucagon receptor (hGluR) antagonists is described. In the process of optimizing glucagon receptor antagonists, we counter-screened against the closeli related human gastric inhibitory polypeptide receptor (hGIPR), and through structure activity analysis, we obtained compounds with low nanomolar affinities toward the hGluR, which were selective against the hGIPR and the human glucagon-like peptide-1 receptor (hGLP-1R). In the best cases, we obtained a >50 fold selectivity for the hGluR over the hGIPR and a > 1000 fold selectivity over the hGLP-1R. A potent and selective glucagon receptor antagonist was demonstrated to inhibit glucagon-induced glycogenolysis in primary rat hepatocytes as well as to lower glucagon-induced hyperolycemia in Sprague-Dawley rats. Furthermore. the compound was shown to lower blood glucose in the ob/ob mouse after oral dosing.

  DOI：

  10.1021/jm7015599

文献信息

• The preparation and biological activity of novel amino acid analogs of butirosin
  作者：T.H. Haskell、R. Rodebaugh、N. Plessas、D. Watson、R.D. Westland

  DOI：10.1016/s0008-6215(00)82782-2

  日期：1973.6

  of the aminocyclitol class of compounds to contain an amino acid in its chemical structure. Complete structural assignments for butirosin A and B have been described 2 and are shown in formula 1 . The amino acid, which is connected by an amide linkage to N 1 of the deoxystreptamine moiety, was found to be the unique ( S )-()-4-amino-2-hydroxybutyric acid 2 . The butirosins have marked activity against

  摘要氨基糖苷类抗生素butirosin（1）的氨基酸侧链已被化学修饰。通过四（5，5-二甲基-3-氧代-1-氧-1-环己烯-1-基）衍生物的碱水解除去（S）-（）-4-氨基-2-羟基丁酰基侧链。将得到的脱酰的三取代的衍生物3与多种单和多官能氨基酸再酰化。然后通过氯气除去环己烯基保护基，并通过色谱分离新的类似物。用包括铜绿假单胞菌在内的五种微生物确定了构效关系。鉴定出表现出针对假单胞菌的最大效力的特定侧链结构。Butirosin 1（一种新的氨基糖苷类抗生素复合物，由环状芽孢杆菌NRRL B-3312和B-3313的粘液状菌株产生，氨基环醇类化合物的第一个实例是在其化学结构中包含氨基酸的化合物。Butirosin A和B的完整结构分配已在2中进行了描述，并在式1中显示。通过酰胺键连接到脱氧链胺基部分的N 1上的氨基酸被发现是独特的（S）-（-4-）-4-氨基-2-羟基丁酸2。Butiros
• Glucagon antagonists/inverse agonists
  申请人：——

  公开号：US20020143186A1

  公开（公告）日：2002-10-03

  A novel class of compounds, which act to antagonize the action of the glucagon hormone on the glucagon receptor. Owing to their antagonizing effect of the glucagon receptor the compounds may be suitable for the treatment and/or prevention of any diseases and disorders, wherein a glucagon antagonistic action is beneficial, such as hyperglycemia, Type 1 diabetes, Type 2 diabetes, disorders of the lipid metabolism, such as dyslipidemia, and obesity.

  一种新型化合物类别，其作用是拮抗胰高血糖素激素对胰高血糖素受体的作用。由于这些化合物对胰高血糖素受体的拮抗作用，这些化合物可能适用于治疗和/或预防任何胰高血糖素拮抗作用有益的疾病和疾病，如高血糖症、1型糖尿病、2型糖尿病、脂质代谢紊乱疾病，如血脂异常和肥胖症。
• [EN] GLUCAGON ANTAGONISTS/INVERSE AGONISTS<br/>[FR] ANTAGONISTES/AGONISTES INVERSES DU GLUCAGON
  申请人：NOVO NORDISK AS

  公开号：WO2002000612A1

  公开（公告）日：2002-01-03

  A novel class of compounds, which act to antagonize the action of the glucagon hormone on the glucagon receptor. Owing to their antagonizing effect of the glucagon receptor the compounds may be suitable for the treatment and/or prevention of any diseases and disorders, wherein a glucagon antagonistic action is beneficial, such as hyperglycemia, Type 1 diabetes, Type 2 diabetes, disorders of the lipid metabolism and obesity.

  一种新型化合物，其作用是对抗胰高血糖素激素对胰高血糖素受体的作用。由于这些化合物对胰高血糖素受体的拮抗作用，因此这些化合物可能适用于治疗和/或预防任何需要胰高血糖素拮抗作用的疾病和障碍，例如高血糖症、1型糖尿病、2型糖尿病、脂质代谢障碍和肥胖症。
• Total Synthesis of (−)-Levesquamide
  作者：Yingjun Jiang、Xiaoyu Liu、Wenxuan Li、Xiaozhen Jiao、Ping Xie

  DOI：10.1021/acs.joc.2c03066

  日期：2023.3.17

  The total synthesis of levesquamide, a natural product with an unprecedented pentasubstituted pyridine-isothiazolinone skeleton, has been accomplished from kojic acid for the first time. The key features of the synthesis include a Suzuki coupling reaction between bromopyranone and oxazolyl borate fragments, a copper-mediated introduction of a thioether, a mild hydrolysis of a pyridine 2-N-methoxyamide

  levesquamide 是一种具有前所未有的五取代吡啶-异噻唑啉酮骨架的天然产物，首次以曲酸为原料实现了全合成。该合成的主要特征包括溴吡喃酮和恶唑基硼酸酯片段之间的铃木偶联反应、铜介导的硫醚引入、吡啶 2-N-甲氧基酰胺的温和水解以及叔丁基的Pummerer型环化亚砜形成天然产物的关键吡啶-异噻唑啉酮单元。
• WO2007/57767
  申请人：——

  公开号：——

  公开（公告）日：——