(+/-)-hexahydrofuro[2,3-b]furan-3-ol | 109789-19-7

• 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: (+/-)-hexahydrofuro[2,3-b]furan-3-ol
• 英文别名: (3aR,6aS)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-ol
• CAS: 109789-19-7
• 化学式: C₆H₁₀O₃
• 分子量: 130.144
• InChiKey: RCDXYCHYMULCDZ-QBQQJPCDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  9
• 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：

  (+/-)-hexahydrofuro[2,3-b]furan-3-ol 在 sodium hypochlorite 、 sodium tetrahydroborate 、 2,2,6,6-四甲基哌啶氧化物 、 四丁基氯化铵 、 乙酸酐 、 碳酸氢钠 、 potassium bromide 作用下， 以 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 49.0h， 生成 (3R,3AS,6AR)-六氢呋喃并[2,3-B]呋喃-3-基(4-硝基苯基)碳酸盐
  参考文献：
  名称：

  Research and Development of an Efficient Synthesis of Hexahydrofuro[2,3-b]furan-3-ol Moiety—A Key Component of the HIV Protease Inhibitor Candidates

  摘要：

  A highly efficient method for synthesizing racemic hexahydrofuro[2,3-b]furan-3-ol has been developed utilizing a lanthanide catalyst, such as Yb(fod)(3), to promote condensation of 2,3-dihydrofuran and glycolaldehyde dimer. Access to either optically enriched enantiomer of bisfuran alcohol can be obtained by using this method employing chiral ligands with the lanthanide catalyst. In support of Gilead Sciences' protease inhibitor project, this method has been demonstrated to be a robust and scalable process with potential application for the construction of a variety of furo[2,3-b]furan derivatives.

  DOI：

  10.1021/op700160a
• 作为产物：
  描述：

  (2R,3S)-3-溴-2-(2-丙炔-1-氧基)四氢呋喃 在 lithium aluminium tetrahydride 、 二甲基硫 、 偶氮二异丁腈 、 三正丁基氢锡 、 臭氧 作用下， 以 乙醚 、 二氯甲烷 、 苯 为溶剂， 反应 8.0h， 生成 (+/-)-hexahydrofuro[2,3-b]furan-3-ol
  参考文献：
  名称：

  通过自由基环化制取全氢和四氢呋喃-2,3b呋喃的新途径

  摘要：

  通过不饱和溴缩醛的自由基环化，已高产率地制备了Perhydrofuro-2,3b呋喃。描述了它们向四氢衍生物的转化以及碘乙酸三丁锡自由基自由基化成2，3-二氢呋喃的方法。

  DOI：

  10.1016/s0040-4039(00)83861-7

文献信息

• WO2007/126812
  申请人：——

  公开号：——

  公开（公告）日：——
• Highly diastereo- and enantioselective catalytic synthesis of the bis-tetrahydrofuran alcohol of Brecanavir and Darunavir
  作者：David M. Black、Roman Davis、Brian D. Doan、Tom C. Lovelace、Alan Millar、Jennifer F. Toczko、Shiping Xie

  DOI：10.1016/j.tetasy.2008.07.037

  日期：2008.9

  An efficient highly diastereo- and enantioselective synthesis of the bis-tetrahydrofuran (bis-THF) alcohol of several HIV protease inhibitors, including Brecanavir and Darunavir, has been achieved utilizing an Evans Mukaiyama aldol reaction of (benzyloxy)acetaldehyde and a silyl ketene acetal. The lactone alcohol intermediate from the catalytic aldol reaction was reduced to a lactol. Palladium catalyzed hydrogenolysis removed the benzyl protection and promoted an in situ cyclization to form the epimer of the bis-THF alcohol in a 98:2 diastereomeric ratio and 97:3 enantiomeric ratio. The alcohol epimer was readily converted to the target in two steps by oxidation to a ketone followed by highly selective reduction to the bis-THF alcohol. (C) 2008 Elsevier Ltd. All rights reserved.
• Biocatalytic Resolution of Bis-tetrahydrofuran Alcohol
  作者：Yuri L. Khmelnitsky、Peter C. Michels、Ian C. Cotterill、Michael Eissenstat、Venkataiah Sunku、Venugopal R. Veeramaneni、Hariprasad Cittineni、Gopal R. Kotha、Shyamsunder R. Talasani、Krishna K. Ramanathan、Vakula K. Chitineni、Bhaskar R. Venepalli

  DOI：10.1021/op100254z

  日期：2011.1.21

  A simple and efficient process has been developed to effect the kinetic resolution of the racemic alcohol 2 using immobilized lipase to afford the desired optically pure (R)-bis-tetrahydrofuran (bis-THF) alcohol 3, to facilitate the rapid progression of a clinical candidate. Rapid optimization and development of reproducible and scalable processes are essential to meet aggressive timeframes for preclinical, safety, and early clinical drug development. Process parameters were initially scoped and optimized using a combination of a rational bioprocess screening design and parallel microscale empirical studies, specifically accounting for scale-up and downstream processing considerations. The choices of reaction solvent, acyl donor, and immobilized biocatalyst proved to be critical factors in the design of a conveniently scalable and enantioselective enzymatic resolution process. The improved process was initially validated on 3-g and then 90-g scale in simple impeller-stirred reactors, exhibiting excellent reproducibility. This methodology was successfully implemented on a multikilogram scale to give the target alcohol 3 with >99% ee.
• US8802724B2
  申请人：——

  公开号：US8802724B2

  公开（公告）日：2014-08-12
• [EN] METHOD FOR THE SYNTHESIS OF HEXAHYDROFURO (2, 3-B) FURAN-3-OL COMPOUNDS<br/>[FR] PROCÉDÉ DE SYNTHÈSE DE COMPOSÉS HEXAHYDROFURO(2,3-B)FURAN-3-OL
  申请人：DSM IP ASSETS BV

  公开号：WO2008034598A1

  公开（公告）日：2008-03-27

  [EN] The present invention relates to a method for the synthesis of enantiomerically and diastereomerically enriched hexahydro-furo[2,3-b]furan-3-ol compounds by aldol coupling of two suitable O-protected hydroxyaldehydes and subsequent removal of the protecting groups and (optionally simultaneous) cyclization of the resulting aldol compound and subsequent isolation of the desired compounds. The resulting composition can be further diastereomerically enriched through the intermittent acylation or aroylation of the compound and further optionally using a stereoselective hydrolyzing enzyme.
  [FR] La présente invention concerne un procédé pour la synthèse de composés hexahydro-furo[2,3-b]furan-3-ol enrichis en énantiomères et en diastéréomères par le couplage par aldol de deux hydroxyaldéhydes protégés par O appropriés, l'élimination ultérieure des groupes protecteurs, la cyclisation (facultativement simultanée) du composé aldol résultant, et l'isolement ultérieur des composés désirés. La composition résultante peut être encore enrichie en diastéréomères par l'acylation ou l'aroylation intermittente du composé et, en plus, par l'utilisation facultative à l'aide d'une enzyme hydrolysante stéréosélective.