tert-butyl (3aR,4R,6aS)-4-(aminomethyl)tetrahydro-2,2-dimethyl-5H-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate | 388076-87-7

• 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 (3aR,4R,6aS)-4-(aminomethyl)tetrahydro-2,2-dimethyl-5H-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate
• 英文别名: tert-butyl (3aR,4R,6aS)-4-(aminomethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydro-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate
• CAS: 388076-87-7
• 化学式: C₁₃H₂₄N₂O₄
• 分子量: 272.345
• InChiKey: UTLZBFHUDSDBNM-KXUCPTDWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  74
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl (3aR,4R,6aS)-4-(aminomethyl)tetrahydro-2,2-dimethyl-5H-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate 在 盐酸 作用下， 生成 (2R,3R,4S)-2-(aminomethyl)pyrrolidine-3,4-diol
  参考文献：
  名称：

  Derivatives of (2R,3R,4S)-2-Aminomethylpyrrolidine-3,4-diol are selective α-Mannosidase inhibitors

  摘要：

  A collection of (2R,3R,4S)-3,4-dihydroxypyrrolidin-2-yl derivatives have been tested for their inhibitory activities toward 25 glycosidases. Competitive (K-i=7.4 VM) and selective inhibition of alpha -mannosidase from jack bean has been found for (2R,3R,4S)-2-[(benzylamino)methyl]pyrrolidine-3,4-diol and other derivatives. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00477-2
• 作为产物：
  描述：

  tert-butyl (3aR,4R,6aS)-4-[(benzylamino)methyl]tetrahydro-2,2-dimethyl-5H-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate 在 palladium dihydroxide 、 甲烷 氢气 作用下， 以 甲醇 为溶剂， 生成 tert-butyl (3aR,4R,6aS)-4-(aminomethyl)tetrahydro-2,2-dimethyl-5H-[1,3]dioxolo[4,5-c]pyrrole-5-carboxylate
  参考文献：
  名称：

  Derivatives of (2R,3R,4S)-2-Aminomethylpyrrolidine-3,4-diol are selective α-Mannosidase inhibitors

  摘要：

  A collection of (2R,3R,4S)-3,4-dihydroxypyrrolidin-2-yl derivatives have been tested for their inhibitory activities toward 25 glycosidases. Competitive (K-i=7.4 VM) and selective inhibition of alpha -mannosidase from jack bean has been found for (2R,3R,4S)-2-[(benzylamino)methyl]pyrrolidine-3,4-diol and other derivatives. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00477-2

文献信息

• Discovery of AL-GDa62 as a Potential Synthetic Lethal Lead for the Treatment of Gastric Cancer
  作者：Andreas Luxenburger、Nicola Bougen-Zhukov、Michael G. Fraser、Henry Beetham、Lawrence D. Harris、Dorian Schmidt、Scott A. Cameron、Parry J. Guilford、Gary B. Evans

  DOI：10.1021/acs.jmedchem.1c01609

  日期：2021.12.23

  optimize 1. Overall, 63 analogues were synthesized and tested for their SL activity toward isogenic mammary epithelial CDH1-deficient cells (MCF10A-CDH1–/–). Among the 26 compounds with greater cytotoxicity, AL-GDa62 (3) was four-times more potent and more selective than 1 with an EC50 ratio of 1.6. Furthermore, 3 preferentially induced apoptosis in CDH1–/– cells, and Cdh1–/– mammary and gastric organoids

  弥漫性胃癌和小叶乳腺癌是侵袭性恶性肿瘤，通常与肿瘤抑制基因CDH1 的失活突变有关。由CDH1功能障碍引起的合成致死 (SL) 漏洞代表了药物开发的有吸引力的目标。最近，SLEC-11 ( 1 ) 作为 E-钙粘蛋白缺陷细胞中的 SL 前导出现。在这里，我们描述了我们为优化1所做的努力。总体而言，合成了 63 种类似物并测试了它们对同基因乳腺上皮CDH1缺陷细胞 (MCF10A- CDH1 –/– ) 的 SL 活性。在 26 种细胞毒性较大的化合物中，AL-GDa62 ( 3) 的效力和选择性是1的四倍，EC 50比率为 1.6。此外，3优先诱导CDH1 –/–细胞凋亡，并且Cdh1 –/–乳腺和胃类器官在低微摩尔浓度下对3明显更敏感。处理过的 MCF10A -CDH1 –/–细胞蛋白裂解物的热蛋白质组分析显示，3特异性抑制 TCOF1、ARPC5 和 UBC9。在体外，3在低微摩尔浓度下抑制
• Synthesis and -Mannosidase Inhibitory Evaluation of (2R,3R,4S)- and (2S,3R,4S)-2-(Aminomethyl)pyrrolidine-3,4-diol Derivatives
  作者：Florence Popowycz、Sandrine Gerber-Lemaire、Eliazar Rodriguez-García、Catherine Schütz、Pierre Vogel

  DOI：10.1002/hlca.200390153

  日期：2003.6

  The synthesis of 46 derivatives of (2R,3R,4S)-2-(aminomethyl)pyrrolidine-3,4-diol is reported (Scheme 1 and Fig. 3), and their inhibitory activities toward α-mannosidases from jack bean (B) and almonds (A) are evaluated (Table). The most-potent inhibitors are (2R,3R,4S)-2-[([1,1′-biphenyl]-4-ylmethyl)amino]methyl}pyrrolidine-3,4-diol (3fs; IC50(B)=5 μM, Ki=2.5 μM) and (2R,3R,4S)-2-[(1R)-2,3-dihy

  （方案1和图3）报道了（2 R，3 R，4 S）-2-（氨基甲基）吡咯烷-3,4-二醇的46种衍生物的合成及其对α-甘露糖苷酶的抑制活性。评价了豆（B）和杏仁（A）（表）。最有效的抑制剂是（2 R，3 R，4 S）-2-[[（[（1,1'-联苯] -4-基甲基）氨基]甲基}吡咯烷-3,4-二醇（3fs ; IC 50（B）= 5μM，K i = 2.5μM）和（2 R，3 R，4 S）-2-[（1 R）-2，3-二氢-1 H-茚满-1-基氨基]甲基}吡咯烷-3，4-二醇（3fu；IC 50（B）= 17μM，K i = 2.3μM）。制备了（2 S，3 R，4 S）-2-（氨基甲基）吡咯烷-3,4-二醇（6，RH）和三种2-（N-烷基氨基）甲基衍生物6fh，6fs和6f（方案2），并发现它也抑制了来自杰克豆和杏仁的α-甘露糖苷酶（表）。这些系列中最好的抑制剂是（2 S，3 R，4 S）
• A Novel Approach to the Synthesis of N-Substituted 1-<i>C</i>-Aminomethyl Glycofuranosides
  作者：Francisca Cabrera-Escribano、Yolanda Vera-Ayoso、Pastora Borrachero、Manuel Gómez-Guillén、Pierre Vogel

  DOI：10.1055/s-2005-922762

  日期：——

  Reductive amination of formyl C-glycofuranosides, easily available from hexose-derived equatorial-2-OH-glycopyranosides by DAST-promoted ring contraction, afforded N-substituted 1-C-aminomethyl glycofuranosides in most cases in high yields.

  甲酰基 C-呋喃糖苷的还原胺化，很容易通过 DAST 促进的环收缩从己糖衍生的赤道-2-OH-吡喃糖苷中获得，在大多数情况下以高产率提供 N-取代的 1-C-氨基甲基呋喃糖苷。