(S)-5-(methoxymethyl)butyrolactone | 96845-45-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (S)-5-(methoxymethyl)butyrolactone
• 英文别名: (5S)-5-(methoxymethyl)oxolan-2-one
• CAS: 96845-45-3
• 化学式: C₆H₁₀O₃
• 分子量: 130.144
• InChiKey: MUIZJRMCSRLKFM-YFKPBYRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-5-(methoxymethyl)butyrolactone 在 palladium on activated charcoal potassium tert-butylate 、 氢气 、 三甲基铝 、 三乙胺 作用下， 以 正己烷 、 二氯甲烷 、 乙酸乙酯 、 甲苯 为溶剂， 反应 8.0h， 生成 (5R)-1-(o-tert-butyldiphenylsiloxyphenyl)-5-(methoxymethyl)-2-pyrrolidinone
  参考文献：
  名称：

  具有阻转异构结构的光学活性5-取代-2-吡咯烷酮衍生物的合成及其烯醇化物与亲电试剂的3,5-顺式选择性反应

  摘要：

  具有阻转异构性的N-（邻叔丁基苯基）-5-（甲氧基甲基）-2-吡咯烷酮和N-（邻叔丁基二苯基甲硅烷氧基苯基）-5-（甲氧基甲基）-的光学纯形式（> / = 98％ee）由邻位取代的苯胺衍生物和（S）-5-（甲氧基甲基）丁内酯以立体选择性的方式制备具有类似对映异构结构的2-吡咯烷酮。这些内酰胺中的锂烯醇盐与各种亲电试剂反应，然后产物进行脱芳基反应，得到3，5-顺-二取代-2-吡咯烷酮衍生物。

  DOI：

  10.1021/jo991578y

文献信息

• Synthesis of New Optically Active Bis- and Tris(phosphines)
  作者：Henri Brunner、Hans-Jürgen Lautenschlager

  DOI：10.1055/s-1989-27368

  日期：——

  The synthesis of new optically active alkanediylbis- and alkanetriyltris(diphenylphosphines) is described. Easily accessible optically pure lactones and carboxylic acids are reduced to the alcohols, tosylated and reacted with lithium diphenylphosphide to give the corresponding phosphines.

  报道了新型光学活性的烷二基双-和烷三基三(二苯膦)的合成。易于获得的光学纯乳酸和羧酸被还原为醇，经过甲苯磺酰化并与其锂二苯膦反应，得到相应的膦化合物。
• [EN] AROMATIC NITROGEN-CONTAINING 6-MEMBERED RING COMPOUNDS AND THEIR USE<br/>[FR] COMPOSÉS CYCLIQUES AROMATIQUES AZOTÉS À 6 CHAÎNONS ET LEUR UTILISATION
  申请人：MITSUBISHI TANABE PHARMA CORP

  公开号：WO2010030027A1

  公开（公告）日：2010-03-18

  The present invention provides aromatic nitrogen-containing 6-membered ring compounds having execellent PDE10 inhibitory activity. The present invention relates to an aromatic nitrogen-containing 6-membered ring compound represented by the following formula [I0] or a pharmaceutically acceptable salt thereof, a method for preparing the same, and use of said compounds for PDE10 inhibitors, and a pharmaceutical composition comprising said compounds as an active ingredient: Formula [I0] wherein: X1, X2 and X3 each independently are N or CH, and at least two of X1, X2 and X3 are N; A is *-CH=CH-, *-C(Alk)=CH-, *-CH2-CH2- or *-O-CH2- (* is a bond with R1); Alk is a lower alkyl group; Ring B is an optionally substituted nitrogen-containing aliphatic heterocyclic group; R1 is an optionally substituted nitrogen-containing heterocyclic group, a nitrogen-containing heterocyclic moiety of which is a moiety selected from the group consisting of quinoxalinyl, quinolyl, isoquinolyl, quinazolinyl, pyrazinyl, pyrimidinyl and a moiety thereof fused with a 5 to 6-membered aliphatic ring thereto; Y0 is a group selected from the group consisting of the following (1) to (5): (1) an optionally substituted phenyl or an optionally substituted aromatic monocyclic 5 to 6-membered heterocyclic group; (2) an optionally substituted aminocarbonyl; (3) an optionally substituted amino lower alkyl; (4) -O-R2 wherein R2 is hydrogen, an optionally substituted lower alkyl, lower cycloalkyl, aliphatic monocyclic 5 to 6-membered heterocyclic group, or Formula [AA]; (5) mono- or di-substituted amino; provided that, when Y0 is mono- or di-substituted amino, the nitrogen-containing heterocyclic moiety of R1 is not quinoxalinyl or quinolyl.

  本发明提供了具有出色的PDE10抑制活性的芳香氮含6元环化合物。本发明涉及以下式[I0]所代表的芳香氮含6元环化合物或其药学上可接受的盐，其制备方法，以及将所述化合物用作PDE10抑制剂，以及包含所述化合物作为活性成分的药物组合物：式[I0]其中：X1、X2和X3各自独立地为N或CH，并且至少两个X1、X2和X3为N；A为*-CH=CH-，*-C(Alk)=CH-，*-CH2-CH2-或*-O-CH2-（*为与R1的键）；Alk为低碳烷基基团；环B为可选择取代的含氮脂肪杂环基团；R1为可选择取代的含氮杂环基团，其中的氮杂环基团为从喹喔啉基，喹啉基，异喹啉基，喹唑啉基，吡嗪基，嘧啶基中选取的基团，或者与其中的5至6元脂环融合的基团；Y0为从以下（1）到（5）组成的基团：（1）可选择取代的苯基或可选择取代的芳香单环5至6元杂环基团；（2）可选择取代的氨基羰基；（3）可选择取代的氨基低碳烷基；（4）-O-R2其中R2为氢，可选择取代的低碳烷基，低环烷基，脂肪单环5至6元杂环基团，或式[AA]；（5）单取代或双取代氨基；但是，当Y0为单取代或双取代氨基时，R1的含氮杂环基团不是喹喔啉基或喹啉基。
• AROMATIC NITROGEN-CONTAINING 6-MEMBERED RING COMPOUNDS AND THEIR USE
  申请人：Morimoto Hiroshi

  公开号：US20110166135A1

  公开（公告）日：2011-07-07

  The present invention provides aromatic nitrogen-containing 6-membered ring compounds having excellent PDE10 inhibitory activity. The present invention relates to an aromatic nitrogen-containing 6-membered ring compound represented by the following formula [I 0 ] or a pharmaceutically acceptable salt thereof, a method for preparing the same, and use of said compounds for PDE10 inhibitors, and a pharmaceutical composition comprising said compounds as an active ingredient: Formula [I 0 ] wherein: X 1 , X 2 and X 3 each independently are N or CH, and at least two of X 1 , X 2 and X 3 are N; A is *—CH═CH—, *—C(Alk)=CH—, *—CH 2 —CH 2 — or *—O—CH 2 — (* is a bond with R 1 ); Alk is a lower alkyl group; Ring B is an optionally substituted nitrogen-containing aliphatic heterocyclic group; R 1 is an optionally substituted nitrogen-containing heterocyclic group, a nitrogen-containing heterocyclic moiety of which is a moiety selected from the group consisting of quinoxalinyl, quinolyl, isoquinolyl, quinazolinyl, pyrazinyl, pyrimidinyl and a moiety thereof fused with a 5 to 6-membered aliphatic ring thereto; Y 0 is a group selected from the group consisting of the following (1) to (5): (1) an optionally substituted phenyl or an optionally substituted aromatic monocyclic 5 to 6-membered heterocyclic group; (2) an optionally substituted aminocarbonyl; (3) an optionally substituted amino lower alkyl; (4) —O—R 2 wherein R 2 is hydrogen, an optionally substituted lower alkyl, lower cycloalkyl, aliphatic monocyclic 5 to 6-membered heterocyclic group, or Formula [AA]; (5) mono- or di-substituted amino; provided that, when Y 0 is mono- or di-substituted amino, the nitrogen-containing heterocyclic moiety of R 1 is not quinoxalinyl or quinolyl.

  本发明提供了具有优异的PDE10抑制活性的芳香族含氮6元环化合物。本发明涉及以下式[I0]或其药学上可接受的盐，其为一种芳香族含氮6元环化合物，以及其制备方法，用于PDE10抑制剂的化合物和包含该化合物作为活性成分的药物组合物：式[I0]其中：X1、X2和X3各自独立地为N或CH，且至少两个X1、X2和X3为N；A为*—CH═CH—、*—C(Alk)=CH—、*—CH2—CH2—或*—O—CH2—（*为R1的键）；Alk为低碳基；环B为可选取代的含氮脂肪族杂环基；R1为可选取代的含氮杂环基，其中含氮杂环基是从喹啉基、喹啉基、异喹啉基、喹唑啉基、吡嗪基、嘧啶基和它们与5至6元脂环环融合的基中选择的基；Y0为从以下组合中选择的基（1）到（5）：（1）可选取代的苯基或可选取代的芳香单环5至6元杂环基；（2）可选取代的氨基甲酰基；（3）可选取代的氨基低碳基；（4）—O—R2，其中R2为氢、可选取代的低碳基、低环烷基、脂肪单环5至6元杂环基或式[AA]；（5）单取代或双取代的氨基；但当Y0为单取代或双取代的氨基时，R1的含氮杂环基不是喹啉基或喹啉基。
• Stereoselective synthesis of an optically active axially chiral lactam and its reaction with some electrophiles
  作者：Masao Fujita、Osamu Kitagawa、Hirotaka Izawa、Akira Dobashi、Haruhiko Fukaya、Takeo Taguchi

  DOI：10.1016/s0040-4039(99)00051-9

  日期：1999.3

  An optically active form (≥ 98%ee) of N-(ortho-tert-butylphenyl)-5-methoxymethyl-2-pyrrolidinone 3 having axial chirality was prepared from ortho-tert-butylaniline and (S)-5-(methoxymethyl)butylolactone in short steps and a completely stereoselective manner. The reactions of Li-enolate from lactam 3 with various electrophiles proceeded with 3,5-cis-selectivity.

  由邻叔丁基苯胺和（S）-5-（甲氧基甲基）制备具有轴向手性的N-（邻叔丁基苯基）-5-甲氧基甲基-2-吡咯烷酮3的旋光形式（≥98％ee ）丁内酯可在短时间内以完全立体选择性的方式进行。来自内酰胺3的烯醇式锂与各种亲电试剂的反应以3，5-顺式选择性进行。
• Total Synthesis and Anti-inflammatory Activity of Stemoamide-Type Alkaloids Including Totally Substituted Butenolides and Pyrroles
  作者：Yasuki Soda、Yasukazu Sugiyama、Shunsei Sato、Kana Shibuya、Junya Saegusa、Tomoe Matagawa、Sayaka Kawano、Makoto Yoritate、Keisuke Fukaya、Daisuke Urabe、Takeshi Oishi、Kento Mori、Siro Simizu、Noritaka Chida、Takaaki Sato

  DOI：10.1055/a-1941-8680

  日期：2023.2

  Totally substituted butenolide including two tetrasubstituted olefins is a distinct structural motif seen in Stemona alkaloids, but efficient methods for its synthesis are not well developed. As an ongoing program aimed at the collective total synthesis of the stemoamide group, we report a stereodivergent method to give either (E)- or (Z)-totally substituted butenolide from the same intermediate. While

  包括两个四取代烯烃的完全取代的丁烯内酯是百部生物碱中独特的结构基序，但其合成的有效方法尚未得到很好的发展。作为一项针对茎酰胺基团的集体全合成的正在进行的计划，我们报告了一种立体发散方法，可以从同一中间体中得到 ( E )- 或 ( Z )-全取代的丁烯内酯。虽然通过 E1 型机制 AgOTf 介导的消除导致形成动力学 ( Z )-四取代烯烃，但随后 TfOH 介导的异构化产生热力学 ( E )-四取代烯烃。吡咯环是在Stemona中发现的另一个重要结构生物碱。用MnO 2直接氧化吡咯烷环并仔细纯化得到吡咯基团，而内酯基团中的立体中心没有异构化。这两种方法使我们能够合成一系列干酰胺类生物碱，包括三环、四环和五环框架。通过抑制巨噬细胞系 RAW264.7 中 iNOS 表达的抗炎活性表明，没有细胞毒性的最有效的抗炎化合物是原甾体素，其由包括完全取代的丁烯内酯在内的五环框架组成。