(2R,3R,4R)-2-benzyloxymethyl-3,4-dibenzyloxy-1-(2-hydroxyethyl)-pyrrolidine | 188905-38-6

• 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: (2R,3R,4R)-2-benzyloxymethyl-3,4-dibenzyloxy-1-(2-hydroxyethyl)-pyrrolidine
• 英文别名: N-(2-hydroxyethyl)-2,3,5-tri-O-benzyl-1,4-dideoxy-1,4-imino-D-arabinitol；2-(2R,3R,4R)-3,4-bis(benzyloxy)-2-[(benzyloxy)methyl]-1-[(2-hydroxy)ethyl]-1H-pyrrolidine；2-{(2R,3R,4R)-3,4-bis(benzyloxy)-2-[(benzyloxy)methyl]pyrrolidin-1-yl}ethanol；(2R,3R,4R)-3,4-dibenzyloxy-2-benzyloxymethyl-1-(2-hydroxyethyl)pyrrolidine；N-hydroxyethyl-2,3,5-tri-O-benzyl-1,4-dideoxy-1,4-imino-D-arabinitol；2-[(2R,3R,4R)-3,4-bis(phenylmethoxy)-2-(phenylmethoxymethyl)pyrrolidin-1-yl]ethanol
• CAS: 188905-38-6
• 化学式: C₂₈H₃₃NO₄
• 分子量: 447.574
• InChiKey: OPDLDNVTAURDGW-JCYYIGJDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  33
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,3R,4R)-2-benzyloxymethyl-3,4-dibenzyloxy-1-(2-hydroxyethyl)-pyrrolidine 在 偶氮二甲酸二异丙酯 、 叠氮磷酸二苯酯 、 三苯基膦 作用下， 以 乙醚 为溶剂， 反应 2.5h， 以88%的产率得到(2R,3R,4R)-1-(2-azidoethyl)-3,4-bis(benzyloxy)-2-[(benzyloxy)methyl]pyrrolidine
  参考文献：
  名称：

  Dual targeting of PTP1B and glucosidases with new bifunctional iminosugar inhibitors to address type 2 diabetes

  摘要：

  The diffusion of type 2 diabetes (T2D) throughout the world represents one of the most important health problems of this century. Patients suffering from this disease can currently be treated with numerous oral anti-hyperglycaemic drugs, but none is capable of reproducing the physiological action of insulin and, in several cases, they induce severe side effects. Developing new anti-diabetic drugs remains one of the most urgent challenges of the pharmaceutical industry. Multi-target drugs could offer new therapeutic opportunities for the treatment of T2D, and the reported data on type 2 diabetic mice models indicate that these drugs could be more effective and have fewer side effects than mono-target drugs. alpha-Glucosidases and Protein Tyrosine Phosphatase 1B (PTP1B) are considered important targets for the treatment of T2D: the first digest oligo- and disaccharides in the gut, while the latter regulates the insulin-signaling pathway. With the aim of generating new drugs able to target both enzymes, we synthesized a series of bifunctional compounds bearing both a nitro aromatic group and an iminosugar moiety. The results of tests carried out both in vitro and in a cell-based model, show that these bifunctional compounds maintain activity on both target enzymes and, more importantly, show a good insulin-mimetic activity, increasing phosphorylation levels of Akt in the absence of insulin stimulation. These compounds could be used to develop a new generation of anti-hyperglycemic drugs useful for the treatment of patients affected by T2D.

  DOI：

  10.1016/j.bioorg.2019.03.053
• 作为产物：
  描述：

  (3S,4R,5R)-5-benzyloxymethyl-3,4-dibenzyloxy-1-(4-methoxybenzyl)-pyrrolidin-2-one 在 ammonium cerium(IV) nitrate 、 dimethyl sulfide borane 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙腈 为溶剂， 反应 53.5h， 生成 (2R,3R,4R)-2-benzyloxymethyl-3,4-dibenzyloxy-1-(2-hydroxyethyl)-pyrrolidine
  参考文献：
  名称：

  A versatile approach to pyrrolidine azasugars and homoazasugars based on a highly diastereoselective reductive benzyloxymethylation of protected tartarimide

  摘要：

  A highly diastereoselective synthesis of enantio-enriched all trans-3,4-dibenzyloxyl-5-benzyloxymethyl-2-pyrrolidinone 13a was developed based on SmI2-mediated benzyloxymethylation of O,O'-dibenzyltartarimide. The versatility of 13a and its antipode as the key building blocks for the asymmetric synthesis of pyrrolidine azasugars and homoazasugars has been demonstrated by elaborating them into naturally occurring DAB 1 (1), LAB 1 (2), N-hydroxyethyl-DAB 1 (4), 6-deoxy-DMDP 7, and 5-epi-radicamine B 36 as well as the reductive ring-opening product 35. (c) 2007 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tet.2007.02.087
• 作为试剂：
  描述：

  (2R,3R,4R)-3,4-dibenzyloxy-2-benzyloxy-methyl-1-cyclopropylmethylpyrrolidine, hydrochloride 、 2,3,5-tri-O-benzyl-1,4-dideoxy-1,4-imino-D-arabinitol 、 2-氯乙醇 在 (2R,3R,4R)-2-benzyloxymethyl-3,4-dibenzyloxy-1-(2-hydroxyethyl)-pyrrolidine 作用下， 以(2R,3R,4R)-3,4-Dibenzyloxy-2-benzyloxymethyl-1-(2-hydroxyethyl)pyrrolidine was obtained as a golden oil (0.48 g, yield: 85%)的产率得到(2R,3R,4R)-2-benzyloxymethyl-3,4-dibenzyloxy-1-(2-hydroxyethyl)-pyrrolidine
  参考文献：
  名称：

  Method of inhibiting liver glycogen phosphorylase with 2-alkylpyrrolidines

  摘要：

  本发明涉及(2R,3R,4R)-3,4-二羟基-2-羟甲基吡咯烷和其他取代的2-甲基吡咯烷及其用于抑制肝糖原磷酸化酶。

  公开号：

  US06451836B1

文献信息

• GLYCOSIDASE INHIBITORS AND METHODS OF SYNTHESIZING SAME
  申请人：Pinto M. Brian

  公开号：US20070244184A1

  公开（公告）日：2007-10-18

  The compounds of the present invention relate to chain-extended and chain-modified analogues of salacinol, including embodiments where the sulfate moiety has been substituted with a carboxylate or phosphate moiety. In other embodiments the sulfate moiety has been shifted by one carbon atom in the zwitterionic structure. In another embodiment the polyhydroxylated side chain may be replaced with a lipophilic alkyl chain and a suitable counterion. The invention also encompasses methods for synthesizing the salacinol analogues and using the analogues for enzyme inhibition applications.

  本发明的化合物涉及与salacinol的链延伸和链修饰类似物，包括其中硫酸酯基团已被羧酸酯基团或磷酸酯基团取代的实施例。在其他实施例中，硫酸酯基团在带电离结构中已被向一碳原子移位。在另一实施例中，多羟基侧链可以被脂溶性烷基链和适当的对离子取代。本发明还涵盖了合成salacinol类似物的方法以及将这些类似物用于酶抑制应用的方法。
• Probing the Influence of Linker Length and Flexibility in the Design and Synthesis of New Trehalase Inhibitors
  作者：Giampiero D’Adamio、Matilde Forcella、Paola Fusi、Paolo Parenti、Camilla Matassini、Xhenti Ferhati、Costanza Vanni、Francesca Cardona

  DOI：10.3390/molecules23020436

  日期：——

  synthesize new trehalase inhibitors selective towards the insect trehalase versus the porcine trehalase, in view of their application as potentially non-toxic insecticides and fungicides. The synthesis of a new pseudodisaccharide mimetic 8, by means of a stereoselective α-glucosylation of the key pyrrolizidine intermediate 13, was accomplished. The activity of compound 8 as trehalase inhibitor towards

  鉴于它们作为潜在的无毒杀虫剂和杀菌剂的应用，这项工作旨在合成对昆虫海藻糖酶与猪海藻糖酶具有选择性的新型海藻糖酶抑制剂。通过对关键的吡咯里西啶中间体 13 进行立体选择性 α-葡萄糖基化，合成了一种新的假二糖模拟物 8。评价了化合物8作为海藻糖酶抑制剂对C. riparius trehalase的活性，结果表明8在μM范围内具有活性，并且对昆虫海藻糖酶显示出良好的选择性。为了减少合成步骤的总数，合成了更简单、更灵活的双糖模拟物 9-11，其带有吡咯烷核而不是吡咯里西啶核。生物学数据显示接头链的长度在诱导抑制特性中的关键作用，因为只有带有两个碳原子接头链的化合物 9（α，β-混合物）保持作为海藻糖酶抑制剂的活性。葡萄糖基供体保护基团的适当变化允许 β-葡萄糖苷 9β 的立体选择性合成，其在低微摩尔范围内具有活性 (IC50 = 0.78 μM)，并且比 9α 对昆虫海藻糖酶。
• 2-alkylpyrrolidines
  申请人：Novo Nordisk A/S

  公开号：US05854272A1

  公开（公告）日：1998-12-29

  The present invention relates to (2R,3R,4R)-3,4-dihydroxy-2-hydroxymethylpyrrolidine and other substituted 2-methylpyrrolidines and their use for the treatment of diabetes.

  本发明涉及（2R，3R，4R）-3，4-二羟基-2-羟甲基吡咯烷及其他取代的2-甲基吡咯烷，以及它们在糖尿病治疗方面的应用。
• Use of 3,4-dihydroxy-2-hydroxymethylpyrrolidine for the treatment of diabetes
  申请人：NOVO NORDISK A/S

  公开号：EP0884050A1

  公开（公告）日：1998-12-16

  (2R,3R,4R)-3,4-dihydroxy-2-hydroxymethylpyrrolidine and other substituted 2-methylpyrrolidines can be used for the treatment of diabetes.

  (2R,3R,4R)-3,4-二羟基-2-羟甲基吡咯烷和其他取代的 2-甲基吡咯烷可用于治疗糖尿病。
• Use of 2-alkylpyrrolidines for the treatment of diabetes
  申请人：NOVO NORDISK A/S

  公开号：EP1040827A2

  公开（公告）日：2000-10-04

  (2R,3R,4R)-3,4-dihydroxy-2-hydroxymethylpyrrolidine and other substituted 2-methylpyrrolidines can be used for the treatment of diabetes.

  (2R,3R,4R)-3,4-二羟基-2-羟甲基吡咯烷和其他取代的 2-甲基吡咯烷可用于治疗糖尿病。