(4R,6s)-6-甲基-5,6-二氢-4H-噻吩并[2,3-b]硫代吡喃-4-醇 | 147086-80-4

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 中文名称: (4R,6s)-6-甲基-5,6-二氢-4H-噻吩并[2,3-b]硫代吡喃-4-醇
• 中文别名: (4R,6S)-5,6-二氢-4-羟基-6-甲基噻吩并(2,3-b)噻喃；(4R,6S)-5,6-二氢-4-羟基-6-甲基噻吩并[2,3-B]噻喃
• 英文名称: 5,6-dihydro-(R)-4-hydroxy-(S)-6-methyl-4H-thieno<2,3-b>thiopyran
• 英文别名: (4R,6S)-6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-ol
• CAS: 147086-80-4
• 化学式: C₈H₁₀OS₂
• 分子量: 186.299
• InChiKey: RSJUYFIZTAZAEA-CAHLUQPWSA-N

物化性质

• 熔点：
  98-99℃
• 沸点：
  303.7±42.0 °C(Predicted)
• 密度：
  1.310±0.06 g/cm3 (20 ºC 760 Torr)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  11
• 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：
  73.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4R,6s)-6-甲基-5,6-二氢-4H-噻吩并[2,3-b]硫代吡喃-4-醇 在 氯磺酸 、 ammonium hydroxide 、 sodium tungstate 、 dimethyl sulfide borane 、 硫酸 、 双氧水 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 、 甲苯 为溶剂， 反应 15.5h， 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 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成 (4R,6s)-6-甲基-5,6-二氢-4H-噻吩并[2,3-b]硫代吡喃-4-醇
  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

• Applying Lipase Catalysis to Access the Enantiomers of Dorzolamide Intermediates
  作者：Mihaela C. Turcu、Maria Rantapaju、Liisa T. Kanerva

  DOI：10.1002/ejoc.200900672

  日期：2009.11

  resolution of three dorzolamide intermediates has been studied in the presence of Burkholderia cepacia lipase in organic solvents. All the stereoisomers of 6-methyl-5,6-dihydro-4H-thieno[2,3-b]thiopyran-4-ol were prepared starting from the racemic cis-dihydrothiopyranol intermediate giving first the 4R,6S and 4S,6R enantiomers. Subsequent epimerization and purification of the trans enantiomers by enzymatic

  在有机溶剂中洋葱伯克霍尔德菌脂肪酶存在下研究了三种多佐胺中间体的动力学拆分。6-甲基-5,6-二氢-4H-噻吩并[2,3-b]噻喃-4-醇的所有立体异构体都是从外消旋顺式-二氢噻喃醇中间体开始制备的，首先得到4R,6S和4S,6R对映异构体. 随后通过酶促酰化或醇解对反式对映异构体进行差向异构化和纯化，然后得到顺式对映异构体。顺式-4-羟基-6-甲基-5,6-二氢-4H-噻吩并[2,3-b]噻喃 7,7-二氧化物对映体也通过酶动力学拆分制备。使用脂肪酶对 3-(2-噻吩基硫基) 丁酸乙酯进行动力学拆分可提供中等的对映选择性，但该方法并未用于该底物的制备规模。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
• J. Org. Chem. 1993,58, 1672-1679
  作者：

  DOI：——

  日期：——
• 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.