tert-butyl (R)-4-((benzyloxy)methyl)-5-oxooxazolidine-3-carboxylate | 872414-47-6

• 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: tert-butyl (R)-4-((benzyloxy)methyl)-5-oxooxazolidine-3-carboxylate
• 英文别名: (R)-tert-butyl 4-(benzyloxymethyl)-5-oxooxazolidine-3-carboxylate；tert-butyl (4R)-5-oxo-4-(phenylmethoxymethyl)-1,3-oxazolidine-3-carboxylate
• CAS: 872414-47-6
• 化学式: C₁₆H₂₁NO₅
• 分子量: 307.346
• InChiKey: FOBSSXYPBGSKIG-CYBMUJFWSA-N

物化性质

• 熔点：
  76-78 °C
• 沸点：
  448.7±35.0 °C(Predicted)
• 密度：
  1.186±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (R)-4-((benzyloxy)methyl)-5-oxooxazolidine-3-carboxylate 在 三乙基硅烷 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 醋酸异丙酯 、 水 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  Structure activity studies of the serine-AIB dipeptide domain in 2,3-dihydroisothiazole based growth hormone secretagogues

  摘要：

  A series of growth hormone secretagogues (GHSs) based on 2,3-dihydroisothiazole has been synthesized in the search for a potential treatment of growth hormone deficiency or frailty in the elderly. This paper describes the evaluation of the SAR of the benzyl-D-Ser-aminoisobutyric acid dipeptide fragment. Introduction of substituents in the peptide backbone and in the phenyl ring has been investigated, as well as replacements for the benzyl group and for the AIB residue. A number of modifications resulted in enhanced potency over the parent benzyl-D-Ser-AIB derivative. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.070
• 作为产物：
  描述：

  聚合甲醛 、 N-Boc-O-苄基-D-丝氨酸 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 以90%的产率得到tert-butyl (R)-4-((benzyloxy)methyl)-5-oxooxazolidine-3-carboxylate
  参考文献：
  名称：

  Arylomycin A2 的全合成，一种信号肽酶 I (SPase I) 抑制剂

  摘要：

  以关键的内摩尔为特征，完成了 arylomycin A2 的简明全合成。Suzuki-Miyaura 反应，用于形成 14 元间位环芳烃，并将完全精心设计的肽侧链与大环核心直接偶联。[在 SciFinder (R) 上]

  DOI：

  10.1055/s-2008-1078209

文献信息

• Total Synthesis of Arylomycin A₂, a Signal Peptidase I (SPase I) Inhibitor
  作者：Luc Neuville、Jieping Zhu、Jeremy Dufour

  DOI：10.1055/s-2008-1078209

  日期：——

  A concise total synthesis of arylomycin A2 was accomplished featuring a key intramol. Suzuki-Miyaura reaction for the formation of the 14-membered meta,meta-cyclophane and direct coupling of a fully elaborated peptide side-chain with the macrocyclic core. [on SciFinder (R)]

  以关键的内摩尔为特征，完成了 arylomycin A2 的简明全合成。Suzuki-Miyaura 反应，用于形成 14 元间位环芳烃，并将完全精心设计的肽侧链与大环核心直接偶联。[在 SciFinder (R) 上]
• [EN] MACROCYCLES AS CFTR MODULATORS<br/>[FR] MACROCYCLES EN TANT QUE MODULATEURS DE CFTR
  申请人：IDORSIA PHARMACEUTICALS LTD

  公开号：WO2022194399A1

  公开（公告）日：2022-09-22

  The present invention relates to macrocyclic compounds of Formula (I) wherein Ar1, Ar2, R1, R2, R3, R4, and X are as described in the description, their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of Formula (I), and especially to their use as modulators of CFTR.

  本发明涉及公式（I）的大环化合物，其中Ar1，Ar2，R1，R2，R3，R4和X如描述中所述，它们的制备方法，其药学上可接受的盐以及它们作为药物的用途，包括含有一个或多个公式（I）化合物的药物组合物，特别是它们作为CFTR调节剂的用途。
• Intramolecular Suzuki-Miyaura Reaction for the Total Synthesis of Signal Peptidase Inhibitors, Arylomycins A2 and B2
  作者：Jeremy Dufour、Luc Neuville、Jieping Zhu

  DOI：10.1002/chem.201000924

  日期：2010.9.10

  Development of the total syntheses of arylomycins A1 and B2 is detailed. Key features of our approach include 1) formation of 14‐membered meta,meta‐cyclophane by an intramolecular Suzuki–Miyaura reaction; 2) incorporation of N‐Me‐4‐hydroxyphenylglycine into the cyclization precursor, which avoids the late‐stage low‐yielding N‐methylation step; 3) segment coupling of a fully elaborated peptide side

  详细介绍了arylomycins A 1和B 2的总合成过程。我们方法的主要特征包括：1）通过分子内Suzuki-Miyaura反应形成14元间位，间环烷；2）将N -Me-4-羟基苯甘氨酸掺入环化前体中，避免了后期的低产N-甲基化步骤；3）将完整加工的肽侧链与大环段偶联，从而使合成高度收敛。总体而言，芳基霉素A 2以最长的线性序列从L- Tyr以13个步骤获得，总产率为13％。阿霉素B 2从L -3-硝基Tyr分十步合成，总收率为10％。
• Structure activity studies of the serine-AIB dipeptide domain in 2,3-dihydroisothiazole based growth hormone secretagogues
  作者：Britta Evers、Gerd Ruehter、Martina Berg、Jeffrey A. Dodge、Dirk Hankotius、Ulrike Hary、Louis N. Jungheim、Hans-Juergen Mest、Eva-Maria Martin de la Nava、Michael Mohr、Brian S. Muehl、Soenke Petersen、Birgit Sommer、Grit Riedel-Herold、Mark J. Tebbe、Kenneth J. Thrasher、Silke Voelkers

  DOI：10.1016/j.bmc.2005.07.070

  日期：2005.12

  A series of growth hormone secretagogues (GHSs) based on 2,3-dihydroisothiazole has been synthesized in the search for a potential treatment of growth hormone deficiency or frailty in the elderly. This paper describes the evaluation of the SAR of the benzyl-D-Ser-aminoisobutyric acid dipeptide fragment. Introduction of substituents in the peptide backbone and in the phenyl ring has been investigated, as well as replacements for the benzyl group and for the AIB residue. A number of modifications resulted in enhanced potency over the parent benzyl-D-Ser-AIB derivative. (c) 2005 Elsevier Ltd. All rights reserved.