5,6-dihydro-(R,S)-4-hydroxy-(S)-6-methyl-4H-thieno<2,3-b>thiopyran 7,7-dioxide | 1034290-08-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 硫吡喃类
• 英文名称: 5,6-dihydro-(R,S)-4-hydroxy-(S)-6-methyl-4H-thieno<2,3-b>thiopyran 7,7-dioxide
• 英文别名: (6S)-6-methyl-7,7-dioxo-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-ol
• CAS: 1034290-08-8
• 化学式: C₈H₁₀O₃S₂
• 分子量: 218.298
• InChiKey: NFUQUGUUAUVBMO-DSEUIKHZSA-N

物化性质

• 沸点：
  433.3±45.0 °C(Predicted)
• 密度：
  1.462±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  91
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5,6-dihydro-(R,S)-4-hydroxy-(S)-6-methyl-4H-thieno<2,3-b>thiopyran 7,7-dioxide 在 氯磺酸 、 ammonium hydroxide 、 dimethyl sulfide borane 、 硫酸 作用下， 以 四氢呋喃 为溶剂， 反应 13.0h， 生成 多佐胺-2-6
  参考文献：
  名称：

  An enantioselective synthesis of the topically-active carbonic anhydrase inhibitor MK-0507: 5,6-dihydro-(S)-4-(ethylamino)-(S)-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide hydrochloride

  摘要：

  The key feature in the synthesis of topically-active carbonic anhydrase inhibitor MK-0507 (13b) is a Ritter reaction that exhibits an unexpected tendency to proceed with retention of chirality. This phenomenon was further studied on model compounds free from potential diastereomeric effects. A mechanism involving transannular stabilization of the sp2-hybridized center by sulfone oxygen is proposed with the net result of double inversion. A second key feature in the preferred sequence to MK-0507 involves the classic problem of how to maximize substitution over elimination. This problem manifests itself in the stereospecific alkylation of 2-mercaptothiophene with derivatized methyl (R)-3-hydroxybutyrate and is compounded by a subsequent Michael reaction leading to a loss of product chirality. Results are presented that eliminate this problem.

  DOI：

  10.1021/jo00059a013
• 作为产物：
  描述：

  多佐胺-2-2 在 sodium tungstate 、 lithium aluminium tetrahydride 、 双氧水 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 2.5h， 生成 5,6-dihydro-(R,S)-4-hydroxy-(S)-6-methyl-4H-thieno<2,3-b>thiopyran 7,7-dioxide
  参考文献：
  名称：

  An enantioselective synthesis of the topically-active carbonic anhydrase inhibitor MK-0507: 5,6-dihydro-(S)-4-(ethylamino)-(S)-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide hydrochloride

  摘要：

  The key feature in the synthesis of topically-active carbonic anhydrase inhibitor MK-0507 (13b) is a Ritter reaction that exhibits an unexpected tendency to proceed with retention of chirality. This phenomenon was further studied on model compounds free from potential diastereomeric effects. A mechanism involving transannular stabilization of the sp2-hybridized center by sulfone oxygen is proposed with the net result of double inversion. A second key feature in the preferred sequence to MK-0507 involves the classic problem of how to maximize substitution over elimination. This problem manifests itself in the stereospecific alkylation of 2-mercaptothiophene with derivatized methyl (R)-3-hydroxybutyrate and is compounded by a subsequent Michael reaction leading to a loss of product chirality. Results are presented that eliminate this problem.

  DOI：

  10.1021/jo00059a013

文献信息

• Deoxyfluorination of alcohols with aryl fluorosulfonates
  作者：Xiu Wang、Min Zhou、Qinghe Liu、Chuanfa Ni、Zhongbo Fei、Wei Li、Jinbo Hu

  DOI：10.1039/d1cc02617h

  日期：——

  Aryl fluorosulfonates are developed as a deoxyfluorinating reagent in the transformation of primary and secondary alcohols into the corresponding alkyl fluorides. These reagents feature easy availability, low-cost, high stability and high efficiency. Diverse functionalities including aldehyde, ketone, ester, halogen, nitro, alkene, and alkyne are well tolerated under mild reaction conditions.

  芳基氟磺酸盐被开发用作将伯醇和仲醇转化为相应的烷基氟化物的脱氧氟化试剂。这些试剂具有易得、低成本、高稳定性和高效率的特点。在温和的反应条件下，包括醛、酮、酯、卤素、硝基、烯烃和炔烃在内的多种官能团具有良好的耐受性。
• J. Org. Chem. 1993,58, 1672-1679
  作者：

  DOI：——

  日期：——
• US8927740B2
  申请人：——

  公开号：US8927740B2

  公开（公告）日：2015-01-06
• [EN] TRICYCLIC INHIBITORS OF CARBONIC ANHYDRASE<br/>[FR] INHIBITEURS TRICYCLIQUES D'ANHYDRASE CARBONIQUE
  申请人：PFIZER PROD INC

  公开号：WO2008075148A2

  公开（公告）日：2008-06-26

  [EN] The invention relates to compounds of formula (I) and to pharmaceutically acceptable salts and solvates thereof, wherein R¹, R² and R³ are as defined herein. The invention also relates to methods of treating glaucoma, ocular hypertension, age-related macular degeneration, diabetic macular edema, diabetic retinopathy, hypertensive retinopathy, retinal vasculopathies and intraocular pressure in mammals by administering the compounds of formula (I), and to pharmaceutical compositions which contain the compounds of formula (I) for such treatments. The invention also relates to methods of preparing the compounds of formula (I).
  [FR] L'invention concerne des composés de formule (I) et des sels et solvates pharmaceutiquement acceptables de ceux-ci, R1, R2 et R3 étant tels que définis dans l'invention. L'invention concernent également des procédés de traitement du glaucome, de l'hypertension oculaire, de la dégénérescence maculaire liée au vieillissement, de l'oedème maculaire diabétique, de la rétinopathie diabétique, de la rétinopathie hypertensive, des vasculopathies rétiniennes et de la tension intraoculaire chez des mammifères, par administration des composés de formule (I). L'invention a également pour objet des compositions pharmaceutiques contenant les composés de formule (I), utilisées pour réaliser les traitements sus-mentionnés, ainsi que des procédés de préparation des composés de formule (I).
• An enantioselective synthesis of the topically-active carbonic anhydrase inhibitor MK-0507: 5,6-dihydro-(S)-4-(ethylamino)-(S)-6-methyl-4H-thieno[2,3-b]thiopyran-2-sulfonamide 7,7-dioxide hydrochloride
  作者：Thomas J. Blacklock、Paul Sohar、John W. Butcher、T. Lamanec、E. J. J. Grabowski

  DOI：10.1021/jo00059a013

  日期：1993.3

  The key feature in the synthesis of topically-active carbonic anhydrase inhibitor MK-0507 (13b) is a Ritter reaction that exhibits an unexpected tendency to proceed with retention of chirality. This phenomenon was further studied on model compounds free from potential diastereomeric effects. A mechanism involving transannular stabilization of the sp2-hybridized center by sulfone oxygen is proposed with the net result of double inversion. A second key feature in the preferred sequence to MK-0507 involves the classic problem of how to maximize substitution over elimination. This problem manifests itself in the stereospecific alkylation of 2-mercaptothiophene with derivatized methyl (R)-3-hydroxybutyrate and is compounded by a subsequent Michael reaction leading to a loss of product chirality. Results are presented that eliminate this problem.