benzyl O-(tert-butyl)-L-threoninate | 42406-75-7

• 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: benzyl O-(tert-butyl)-L-threoninate
• 英文别名: (2S,3R)-Benzyl 2-amino-3-(tert-butoxy)butanoate；benzyl (2S,3R)-2-amino-3-[(2-methylpropan-2-yl)oxy]butanoate
• CAS: 42406-75-7
• 化学式: C₁₅H₂₃NO₃
• 分子量: 265.353
• InChiKey: FNWODCNOJWSUQB-YPMHNXCESA-N

物化性质

• 沸点：
  370.6±27.0 °C(Predicted)
• 密度：
  1.052±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl O-(tert-butyl)-L-threoninate 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 33.0h， 生成 N-(((S)-4-amino-1-(2-(N-(tert-butoxycarbonyl)-O-(tert-butyl)-L-seryl)hydrazineyl)-1,4-dioxobutan-2-yl)carbamoyl)-O-(tert-butyl)-L-threonine
  参考文献：
  名称：

  PEPTIDOMIMETIC COMPOUNDS AS IMMUNOMODULATORS

  摘要：

  本发明涉及作为治疗剂的新型肽类似物化合物，能够抑制程序性细胞死亡1（PD1）信号通路。该发明还涉及这些治疗剂的衍生物。该发明还包括利用所述治疗剂和衍生物治疗通过免疫增强来抑制由于PD-1、PD-L1或PD-L2引起的免疫抑制信号的障碍，并使用它们进行治疗的疗法。

  公开号：

  US20130237580A1
• 作为产物：
  描述：

  Fmoc-O-叔丁基-L-苏氨酸 在 caesium carbonate 、 二乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.5h， 生成 benzyl O-(tert-butyl)-L-threoninate
  参考文献：
  名称：

  PEPTIDOMIMETIC COMPOUNDS AS IMMUNOMODULATORS

  摘要：

  本发明涉及作为治疗剂的新型肽类似物化合物，能够抑制程序性细胞死亡1（PD1）信号通路。该发明还涉及这些治疗剂的衍生物。该发明还包括利用所述治疗剂和衍生物治疗通过免疫增强来抑制由于PD-1、PD-L1或PD-L2引起的免疫抑制信号的障碍，并使用它们进行治疗的疗法。

  公开号：

  US20130237580A1

文献信息

• An Atom-Economic Inverse Solid-Phase Peptide Synthesis Using Bn or BcM Esters of Amino Acids
  作者：Jian Li、Yue Zhu、Bo Liu、Feng Tang、Xing Zheng、Wei Huang

  DOI：10.1021/acs.orglett.1c02769

  日期：2021.10.1

  An atom-economic N-to-C-directed solid-phase peptide synthesis is reported that uses benzyl (Bn) or (benzhydryl-carbamoyl)-methyl (BcM) esters of amino acids as the building blocks, which facilitate efficient hydrazinolysis, convenient conversion to acyl azide, and robust amidation with the next amino acid ester. This method is free of coupling reagents and free of protection on the side-chain OH,

  据报道，一种原子经济的 N 到 C 定向的固相肽合成，使用氨基酸的苄基 (Bn) 或 (二苯甲基-氨基甲酰基)-甲基 (BcM) 酯作为构建单元，促进高效肼解，方便转化为酰基叠氮化物，并与下一个氨基酸酯进行稳健的酰胺化。该方法无需偶联试剂，对侧链OH、CO 2 H、CONH2等无保护，因此与基于BOC或Fmoc的C-to-N-相比，原子经济性显着提高定向方法。
• Spirodiepoxides in Total Synthesis:  Epoxomicin
  作者：Sreenivas Katukojvala、Kristin N. Barlett、Stephen D. Lotesta、Lawrence J. Williams

  DOI：10.1021/ja044563c

  日期：2004.12.1

  The first use of the spirodiepoxide functional group in total synthesis, a study culminating in an efficient synthesis of the potent proteasome inhibitor epoxomicin, is described. Spirodiepoxides derived from allenes by oxidation are shown to give syn disubstituted ketones and their derivatives, including ortho ester, oxazoline, azido epoxide, as well as sulfonamide-, amide-, and azide-containing hydroxy

  描述了螺二环氧化物官能团在全合成中的首次使用，该研究最终以有效合成有效的蛋白酶体抑制剂环氧霉素为高潮。通过氧化从丙二烯衍生的螺二环氧化物显示出顺式双取代酮及其衍生物，包括原酸酯、恶唑啉、叠氮环氧化物以及含磺酰胺、酰胺和叠氮化物的羟基酮。
• Influence of steric parameters on the synthesis of tetramates from α-amino-β-alkoxy-esters and Ph3PCCO
  作者：Inga Loke、Natja Park、Karl Kempf、Carsten Jagusch、Rainer Schobert、Sabine Laschat

  DOI：10.1016/j.tet.2011.10.099

  日期：2012.1

  alpha-Aminoesters react with Ph3PCCO in a domino addition-Wittig cyclization sequence affording enantiomerically pure tetramates. In the case of beta-oxo functionalized alpha-aminoesters, e.g., esters of serine, threonine or beta-hydroxyornithine the yields of this reaction depend heavily on the bulkiness of the beta-OR group and on the configuration of beta-carbon atom C-3. Smaller residues and 2R/3R-configured aminoesters give better yields. The alkoxycarbonyl group of the ester moiety and the residue on the N-atom are less important. These findings can be accounted for by assuming an early puckered transition state for the intramolecular ring-closing Wittig reaction. The addition of sub-stoichiometric amounts of benzoic acid or N-hydroxysuccinimide (for acid-sensitive compounds) is advantageous in some cases as it accelerates the formation of the intermediate amide ylides. (C) 2011 Elsevier Ltd. All rights reserved.
• Paulsen, Hans; Adermann, Knut, Liebigs Annalen der Chemie, 1989, p. 751 - 770
  作者：Paulsen, Hans、Adermann, Knut

  DOI：——

  日期：——
• <i>In Vitro</i> Assessment of Putative PD-1/PD-L1 Inhibitors: Suggestions of an Alternative Mode of Action
  作者：Derek J. Blevins、Ronan Hanley、Trevor Bolduc、David A. Powell、Michael Gignac、Kayleigh Walker、Mark D. Carr、Fraser Hof、Jeremy E. Wulff

  DOI：10.1021/acsmedchemlett.9b00221

  日期：2019.8.8

  The programmed cell death protein 1 (PD-1) signaling axis is among the most important therapeutic targets in modern oncology. Aurigene Discovery Technologies Ltd. (Aurigene) has patented a series of peptidomimetic small molecules derived from the PD-1 protein sequence for use in targeting the interaction between PD-1 and its ligand, PD-L1. We evaluated three of Aurigenes most potent compounds in SPR binding assays. Our results showed that these compounds-each of which is known to be potently effective in a splenocyte recovery assay-do not directly inhibit the PD-1/PD-L1 interaction nor do they appear to bind to either of the constituent proteins, indicating that another mechanism is at play. As a result of these studies and upon consideration of structural features within the PD-1/PD-L1 complex, we hypothesize that the Aurigene molecules may interact with a currently unknown protein capable of regulating the PD-1 axis.