(3aR,4R,7aS)-hexahydro-4H-furo[2,3-b]pyran-4-ol | 1262482-22-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃吡喃类
• 英文名称: (3aR,4R,7aS)-hexahydro-4H-furo[2,3-b]pyran-4-ol
• 英文别名: (3aR,4R,7aS)-hexahydro-2H-furo[2,3-b]pyran-4-ol；(3aR,4R,7aS)-3,3a,4,5,6,7a-hexahydro-2H-furo[2,3-b]pyran-4-ol
• CAS: 1262482-22-3
• 化学式: C₇H₁₂O₃
• 分子量: 144.17
• InChiKey: WNEIYKXYAJHJJU-QYNIQEEDSA-N

物化性质

• 沸点：
  277.7±25.0 °C(predicted)
• 密度：
  1.203±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3aR,4R,7aS)-hexahydro-4H-furo[2,3-b]pyran-4-ol 在 吡啶 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 (3aR,4R,7aS)-hexahydro-2H-furo[2,3-b]pyran-4-yl-((2S,3R)-3-Hydroxy-4-(N-isobutyl-4-methoxyphenylsulfonamido)-1-phenylbutan-2-yl)carbamate
  参考文献：
  名称：

  Design and Synthesis of Potent HIV-1 Protease Inhibitors Incorporating Hexahydrofuropyranol-Derived High Affinity P₂ Ligands: Structure−Activity Studies and Biological Evaluation

  摘要：

  The design, synthesis, and evaluation of a new series of hexahydrofuropyranol-derived HIV-1 protease inhibitors are described. We have designed a stereochemically defined hexahydrofuropyranol-derived urethane as the P2-ligand. The current ligand is designed based upon the X-ray structure of la-bound HIV-1 protease. The synthesis of (3aS,4S,7aR)-hexahydro-2H-furo[2,3-b]pyran-4-ol, (-)-7, was carried out in optically active form. Incorporation of this ligand provided inhibitor 35a, which has shown excellent enzyme inhibitory activity and antiviral potency. Our structure activity studies have indicated that the stereochemistry and the position of oxygens in the ligand are important to the observed potency of the inhibitor. Inhibitor 35a has maintained excellent potency against multidrug-resistant HIV-1 variants. An active site model of 35a was created based upon the X-ray structure of 1b-bound HIV-1 protease. The model offers molecular insights regarding ligand-binding site interactions of the hexahydrofuropyranol-derived novel P2-ligand.

  DOI：

  10.1021/jm1012787
• 作为产物：
  描述：

  [(3aR,4R,7aS)-3,3a,4,5,6,7a-hexahydro-2H-furo[2,3-b]pyran-4-yl] acetate 在 甲醇 、 potassium carbonate 作用下， 反应 2.0h， 以97%的产率得到(3aR,4R,7aS)-hexahydro-4H-furo[2,3-b]pyran-4-ol
  参考文献：
  名称：

  光学活性六氢-4H-呋喃酚醇（一种用于HIV-1蛋白酶抑制剂的高亲和力P2配体）的光化学路线。

  摘要：

  我们在这里描述了光学纯的（3aS，4S，7aR）-六氢-4H-呋喃[2,3-b]吡喃-4-醇和（3aR，4R，7aS）-六氢-4H-呋喃[2， 3-b]吡喃-4-醇。这些立体化学定义的杂环对于各种高效的HIV-1蛋白酶抑制剂而言都是重要的高亲和力P2配体。关键步骤涉及有效的Paternò-Büchi[2 + 2]光环加成，催化氢化，酸催化的环化反应以形成外消旋配体醇，以及固定化的Amano脂肪酶PS-30的酶促拆分。获得具有高对映体纯度的旋光配体（-）-6和（+）-6。对映体（-）-6已转化为有效的HIV-1蛋白酶抑制剂3。

  DOI：

  10.1021/acs.joc.9b01361

文献信息

• COMPOUNDS AND METHODS FOR TREATING HIV
  申请人：GHOSH Arun K.

  公开号：US20130289067A1

  公开（公告）日：2013-10-31

  Inhibitors of HIV-1 protease and compositions containing them are described. Use of the inhibitors and compositions containing them to treat HIV, AIDS, and AIDS-related diseases is described.

  本文描述了HIV-1蛋白酶抑制剂及其组合物。描述了使用这些抑制剂和组合物来治疗HIV、艾滋病和艾滋病相关疾病的方法。
• US9024038B2
  申请人：——

  公开号：US9024038B2

  公开（公告）日：2015-05-05
• US9499558B2
  申请人：——

  公开号：US9499558B2

  公开（公告）日：2016-11-22
• Design and Synthesis of Potent HIV-1 Protease Inhibitors Incorporating Hexahydrofuropyranol-Derived High Affinity P₂ Ligands: Structure−Activity Studies and Biological Evaluation
  作者：Arun K. Ghosh、Bruno D. Chapsal、Abigail Baldridge、Melinda P. Steffey、D. Eric Walters、Yasuhiro Koh、Masayuki Amano、Hiroaki Mitsuya

  DOI：10.1021/jm1012787

  日期：2011.1.27

  The design, synthesis, and evaluation of a new series of hexahydrofuropyranol-derived HIV-1 protease inhibitors are described. We have designed a stereochemically defined hexahydrofuropyranol-derived urethane as the P2-ligand. The current ligand is designed based upon the X-ray structure of la-bound HIV-1 protease. The synthesis of (3aS,4S,7aR)-hexahydro-2H-furo[2,3-b]pyran-4-ol, (-)-7, was carried out in optically active form. Incorporation of this ligand provided inhibitor 35a, which has shown excellent enzyme inhibitory activity and antiviral potency. Our structure activity studies have indicated that the stereochemistry and the position of oxygens in the ligand are important to the observed potency of the inhibitor. Inhibitor 35a has maintained excellent potency against multidrug-resistant HIV-1 variants. An active site model of 35a was created based upon the X-ray structure of 1b-bound HIV-1 protease. The model offers molecular insights regarding ligand-binding site interactions of the hexahydrofuropyranol-derived novel P2-ligand.
• A Photochemical Route to Optically Active Hexahydro-4<i>H</i>-furopyranol, a High-Affinity P2 Ligand for HIV-1 Protease Inhibitors
  作者：Arun K. Ghosh、William L. Robinson

  DOI：10.1021/acs.joc.9b01361

  日期：2019.8.2

  We describe here the syntheses of optically pure (3aS,4S,7aR)-hexahydro-4H-furo[2,3-b]pyran-4-ol and (3aR,4R,7aS)-hexahydro-4H-furo[2,3-b]pyran-4-ol. These stereochemically defined heterocycles are important high-affinity P2 ligands for a variety of highly potent HIV-1 protease inhibitors. The key steps involve an efficient Paternò-Büchi [2 + 2] photocycloaddition, catalytic hydrogenation, acid-catalyzed

  我们在这里描述了光学纯的（3aS，4S，7aR）-六氢-4H-呋喃[2,3-b]吡喃-4-醇和（3aR，4R，7aS）-六氢-4H-呋喃[2， 3-b]吡喃-4-醇。这些立体化学定义的杂环对于各种高效的HIV-1蛋白酶抑制剂而言都是重要的高亲和力P2配体。关键步骤涉及有效的Paternò-Büchi[2 + 2]光环加成，催化氢化，酸催化的环化反应以形成外消旋配体醇，以及固定化的Amano脂肪酶PS-30的酶促拆分。获得具有高对映体纯度的旋光配体（-）-6和（+）-6。对映体（-）-6已转化为有效的HIV-1蛋白酶抑制剂3。