tert-butyl (5S)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2-oxo-3-(phenylselanyl)pyrrolidine-1-carboxylate | 293297-95-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: tert-butyl (5S)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2-oxo-3-(phenylselanyl)pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (5S)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-2-oxo-3-phenylselanylpyrrolidine-1-carboxylate
• CAS: 293297-95-7
• 化学式: C₂₂H₃₅NO₄SeSi
• 分子量: 484.57
• InChiKey: POTOUOMZZPDAQZ-ATNAJCNCSA-N

物化性质

• 沸点：
  521.2±50.0 °C(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.36
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  55.84
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (5S)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2-oxo-3-(phenylselanyl)pyrrolidine-1-carboxylate 在 palladium diacetate sodium acetate 、 臭氧 作用下， 以 乙醚 为溶剂， 反应 0.67h， 生成 N-(tert-Butoxycarbonyl)-3-aza-4-(((tert-butyldimethylsilyl)oxy)methyl)bicyclo<3.1.0>hexan-2-one
  参考文献：
  名称：

  Synthesis of four diastereomeric L-2-(carboxycyclopropyl)glycines. Conformationally constrained L-glutamate analogs

  摘要：

  To determine what conformations of L-glutamate (L-Glu) activate that compound's different receptors in the mammalian central nervous system, four diastereomeric L-2-(carboxycyclopropyl)glycines, 1-4, which are conformationally constrained analogues of the extended and folded conformers of L-Glu, were synthesized and subjected to neutrophysiological assay. Compounds 1-4 were efficiently synthesized from chiral amino acids. Cyclopropanation of the (2S)-2-amino-3-butenol derivative 5b gave intermediates for the synthesis of all four diastereomers. Stereoselective cyclopropanation of both the alpha,beta-unsaturated gamma-lactam 16 and the delta-lactone 19 gave precursors of (2S,1'S,2'R)-3 and (2S,1'R,2'S)-4, respectively. Neurophysiological assays of 1-4 performed with the newborn rat spinal cord demonstrated that the compounds induced a variety of depolarizing effects. The results of the assays strongly suggested that the N-methyl-D-aspartic acid (NMDA) receptor is activated by the folded conformer of L-Glu and that the extended conformer of L-Glu activates the metabotropic L-Glu receptor. The four analogous D-2-(carboxycyclopropyl)glycines (D-1-D-4), which were synthesized from (2R)-5b, proved to be NMDA agonists.

  DOI：

  10.1021/jo00013a018
• 作为产物：
  描述：

  L-焦谷氨酸甲酯 在 咪唑 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 25.25h， 生成 tert-butyl (5S)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2-oxo-3-(phenylselanyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  空间受限的l-谷氨酰胺类似物（3 S，4 R）-3,4-二甲基-1-谷氨酰胺和（3 S，4 R）-3,4-二甲基-1-焦谷氨酸的合成与分析

  摘要：

  非环状氨基酸（3 S，4 R）-3,4-二甲基-1-焦谷氨酸和（3 S，4 R）-3,4-二甲基-1-谷氨酰胺-存在于环状大肽肽callipeltin B，callipeltin中A和木瓜酰胺A-是由衍生自1-焦谷氨酸的常见中间体合成的。甲基的非对映选择性引入是通过铜酸酯加成和烯醇化烷基化，然后是C-4甲基取代基的动力学差向异构化来实现的。（3 S，4 R）-3,4-二甲基-1-谷氨酰胺显示侧链的构象限制，这可能与其在天然产物中的生物学功能有关。

  DOI：

  10.1016/s0040-4020(01)00501-4

文献信息

• Structure–Activity Relationship Study of Ionotropic Glutamate Receptor Antagonist (2<i>S</i>,3<i>R</i>)-3-(3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid
  作者：Niels Krogsgaard-Larsen、Morten Storgaard、Charlotte Møller、Charles S. Demmer、Jeanette Hansen、Liwei Han、Rune N. Monrad、Birgitte Nielsen、Daniel Tapken、Darryl S. Pickering、Jette S. Kastrup、Karla Frydenvang、Lennart Bunch

  DOI：10.1021/acs.jmedchem.5b00750

  日期：2015.8.13

  of the broad-range iGluR antagonist (2S,3R)-3-(3-carboxyphenyl)pyrrolidine-2-carboxylic acid (1) by exploring the pharmacological effect of substituents in the 4, 4′, or 5′ positions and the bioisosteric substitution of the distal carboxylic acid for a phosphonic acid moiety. Of particular interest is a hydroxyl group in the 4′ position 2a which induced a preference in binding affinity for homomeric

  在这里，我们通过研究取代基在药物中的药理作用，描述了广泛的iGluR拮抗剂（2 S，3 R）-3-（3-羧苯基）吡咯烷-2-羧酸（1）的第一个结构-活性关系研究。4、4'或5'位置以及末端羧酸的生物等位取代为膦酸部分。特别令人感兴趣的是在4'位置2a上的羟基，该羟基诱导对同型GluK3的结合亲和力优于GluK1（分别为K i = 0.87和4.8μM ）。获得了两个配体结合域的X射线结构：GluA2-LBD中的2e和2f在GluK1-LBD中的分辨率均为1.9Å。相对于具有谷氨酸的结构，化合物2e诱导GluA2-LBD中的D1-D2结构域开放为17.3-18.8°，而2f诱导GluK1-LBD中的结构域开放为17.0-17.5°。2e和2f的吡咯烷-2-羧酸酯部分显示出与海藻酸盐相似的结合模式。2e和2f的3-羧基苯环形成的接触与海藻酸盐中远端羧酸酯的接触相当。
• [EN] AZAQUINAZOLINE PAN-KRAS INHIBITORS<br/>[FR] INHIBITEURS PAN-KRAS D'AZAQUINAZOLINE
  申请人：MIRATI THERAPEUTICS INC

  公开号：WO2022132200A1

  公开（公告）日：2022-06-23

  The present invention relates to compounds that inhibit at least one of KRas G12A, KRas G12C, KRas G12D, KRas G12R, KRas G12S, KRas G12V, KRas G13D and KRas Q61H, pharmaceutical compositions comprising the compounds and methods of use therefor.

  本发明涉及抑制KRas G12A、KRas G12C、KRas G12D、KRas G12R、KRas G12S、KRas G12V、KRas G13D和KRas Q61H中至少一个的化合物，包括该化合物的药物组合物和使用方法。
• WO2008/150364
  申请人：——

  公开号：——

  公开（公告）日：——
• Functionalized pyrrolidine inhibitors of human type II α-mannosidases as anti-cancer agents: Optimizing the fit to the active site
  作者：Hélène Fiaux、Douglas A. Kuntz、Daniela Hoffman、Robert C. Janzer、Sandrine Gerber-Lemaire、David R. Rose、Lucienne Juillerat-Jeanneret

  DOI：10.1016/j.bmc.2008.06.021

  日期：2008.8

  Refining the chemical structure of functionalized pyrrolidine-based inhibitors of Golgi alpha-mannosidase II (GMII) to optimize binding affinity provided a lead molecule that demonstrated nanomolar competitive inhibition of alpha-mannosidases II and an optimal fit in the active site of Drosophila GMII by X-ray crystallography. Esters of this lead compound also inhibited the growth of human glioblastoma and brain-derived endothelial cells more than the growth of non-tumoral human fibroblasts, suggesting their potential for anti-cancer therapy.
• Photoinduced addition of methanol to 5(S)-5-triisopropylsiloxymethyl-N-boc-dihydropyrrole-2(5H)-one: A new route to 4(S), 5(S)-disubstituted pyrrolidin-2-ones
  作者：Michael G.B. Drew、R.John Harrison、John Mann、Allen J. Tench、Robert J. Young

  DOI：10.1016/s0040-4020(98)01094-1

  日期：1999.1

  We describe the photoinduced addition of methanol to 5(S)-5-triisopropylsiloxymethyl-N-boc-dihydropyrrole-2(5H)-one to produce 5(S)-triisopropylsiloxymethyl-4( S)-hydroxymethylpyrrolidine-2-one, and conversion of this into a variety of 4( S), S(S)-pyrrolidine-2-ones. Photoinduced addition of methanol to 5(R)-N-boc-5-amino-dihydropyran-2(5H)-one yielded the unexpected product 4(S)-1'-[2'-hydroxy, 1'-( R)-N-boc-amino]ethyl-tetrahydrofuran-2-one via rearrangement of the initial photoadduct. (C) 1999 Elsevier Science Ltd. All rights reserved.