(3R,3aR,6aS)-perhydrofuro[2,3-b]furan-3-yl acetate | 605653-07-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃类
• 英文名称: (3R,3aR,6aS)-perhydrofuro[2,3-b]furan-3-yl acetate
• 英文别名: [(3aR,4R,6aS)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl] acetate
• CAS: 605653-07-4
• 化学式: C₈H₁₂O₄
• 分子量: 172.181
• InChiKey: RCXLRBOCGWECNI-CSMHCCOUSA-N

物化性质

• 沸点：
  233.8±30.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3R,3aR,6aS)-perhydrofuro[2,3-b]furan-3-yl acetate 在 potassium carbonate 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 BISTHFHNS衍生物3
  参考文献：
  名称：

  Discovery and Selection of TMC114, a Next Generation HIV-1 Protease Inhibitor

  摘要：

  The screening of known HIV-1 protease inhibitors against a panel of multi-drug-resistant viruses revealed the potent activity of TMC126 on drug-resistant mutants. In comparison to amprenavir, the improved affinity of TMC126 is largely the result of one extra hydrogen bond to the backbone of the protein in the P2 pocket. Modification of the substitution pattern on the phenylsulfonamide P2 ' substituent of TMC126 created an interesting SAR, with the close analogue TMC114 being found to have a similar antiviral activity against the mutant and the wild-type viruses. X-ray and thermodynamic studies on both wild-type and mutant enzymes showed an extremely high enthalpy driven affinity of TMC114 for HIV-1 protease. In vitro selection of mutants resistant to TMC 114 starting from wild-type virus proved to be extremely difficult; this was not the case for other close analogues. Therefore, the extra H-bond to the backbone in the P2 pocket cannot be the only explanation for the interesting antiviral profile of TMC114. Absorption studies in animals indicated that TMC114 has pharmacokinetic properties comparable to currently approved HIV-1 protease inhibitors.

  DOI：

  10.1021/jm049560p
• 作为产物：
  描述：

  六氢呋喃并[2,3-b]呋喃-3-醇 在 偶氮二甲酸二异丙酯 、 potassium carbonate 、 三苯基膦 作用下， 以 乙醇 为溶剂， 生成 (3R,3aR,6aS)-perhydrofuro[2,3-b]furan-3-yl acetate
  参考文献：
  名称：

  Discovery and Selection of TMC114, a Next Generation HIV-1 Protease Inhibitor

  摘要：

  The screening of known HIV-1 protease inhibitors against a panel of multi-drug-resistant viruses revealed the potent activity of TMC126 on drug-resistant mutants. In comparison to amprenavir, the improved affinity of TMC126 is largely the result of one extra hydrogen bond to the backbone of the protein in the P2 pocket. Modification of the substitution pattern on the phenylsulfonamide P2 ' substituent of TMC126 created an interesting SAR, with the close analogue TMC114 being found to have a similar antiviral activity against the mutant and the wild-type viruses. X-ray and thermodynamic studies on both wild-type and mutant enzymes showed an extremely high enthalpy driven affinity of TMC114 for HIV-1 protease. In vitro selection of mutants resistant to TMC 114 starting from wild-type virus proved to be extremely difficult; this was not the case for other close analogues. Therefore, the extra H-bond to the backbone in the P2 pocket cannot be the only explanation for the interesting antiviral profile of TMC114. Absorption studies in animals indicated that TMC114 has pharmacokinetic properties comparable to currently approved HIV-1 protease inhibitors.

  DOI：

  10.1021/jm049560p

文献信息

• Stereoselective Synthesis of<i>cis</i>-Fused Perhydrofuro[2,3-<i>b</i>]furan Derivatives from Sugar-Derived Allyl Vinyl Ethers
  作者：Perali Ramu Sridhar、Gadi Madhusudhan Reddy、Kalapati Seshadri

  DOI：10.1002/ejoc.201200898

  日期：2012.11

  stereoselective methodology has been developed for the construction of cis-fused perhydrofuro[2,3-b]furans, via 3-C-branched glycal derivatives, involving Claisen rearrangement of sugar-derived allyl vinyl ethers, followed by a one-pot ozonolysis and acid-mediated acetalization. The methodology was used for the stereoselective synthesis of the P2 ligand in the recently FDA approved HIV protease inhibitor darunavir

  已经开发了一种立体选择性方法来构建顺式稠合的全氢呋喃 [2,3-b] 呋喃，通过 3-C-支链的糖衍生物，涉及糖衍生的烯丙基乙烯基醚的克莱森重排，然后进行一锅臭氧分解和酸介导的缩醛化。该方法用于立体选择性合成最近 FDA 批准的 HIV 蛋白酶抑制剂达芦那韦 (Prezista) 中的 P2 配体。该方法还成功地用于合成顺式稠合的全氢-5-氧代呋喃 [2,3-b] 呋喃衍生物。
• Process for preparing protease inhibitor intermediates
  申请人：——

  公开号：US20040204595A1

  公开（公告）日：2004-10-14

  The present invention includes a method for preparing cyclic alcohols. The method includes a reduction, deprotection, and rearrangement scheme. The present invention further provides a method of preparation of an intermediate useful in the synthesis of compounds that function as inhibitors of the aspartyl protease enzyme of human immunodeficiency virus (HIV).

  本发明涉及一种制备环状醇的方法。该方法包括还原、去保护和重排方案。本发明还提供了一种制备中间体的方法，该中间体在合成作为人类免疫缺陷病毒（HIV）天冬氨酸蛋白酶酶抑制剂的化合物中发挥作用。
• PROCESS FOR PREPARATION OF HIV PROTEASE INHIBITORS
  申请人：GILEAD SCIENCES, INC.

  公开号：EP1999133B1

  公开（公告）日：2013-08-21
• EP2570416B1
  申请人：——

  公开号：EP2570416B1

  公开（公告）日：2016-03-16
• Process for preparation of HIV protease inhibitors
  申请人：Crawford R. Kenneth

  公开号：US20080004242A1

  公开（公告）日：2008-01-03

  A process for the synthesis of bisfuran intermediates useful for preparing antiviral HIV protease inhibitor compounds is hereby disclosed