(3S,4R)-Methyl 4-hydroxytetrahydro-2H-thiopyran-3-carboxylate | 84230-94-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: (3S,4R)-Methyl 4-hydroxytetrahydro-2H-thiopyran-3-carboxylate
• 英文别名: (3S,4R)-4-Hydroxy-3-methoxycarbonyltetrahydrothiopyrane；methyl (3S,4R)-4-hydroxythiane-3-carboxylate
• CAS: 84230-94-4；87206-45-9
• 化学式: C₇H₁₂O₃S
• 分子量: 176.236
• InChiKey: WCYCFRFETLXIJS-NTSWFWBYSA-N

物化性质

• 沸点：
  286.2±40.0 °C(Predicted)
• 密度：
  1.254±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3S,4R)-Methyl 4-hydroxytetrahydro-2H-thiopyran-3-carboxylate 在 palladium on activated charcoal 哌啶 、 咪唑 、 sodium hydroxide 、 potassium permanganate 、 sodium periodate 、 正丁基锂 、 二苯基膦叠氮化物 、 四丁基氟化铵 、 氢气 、 三乙酰氧基硼氢化钠 、 碳酸氢钠 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 、 乙腈 为溶剂， 60.0 ℃ 、101.33 kPa 条件下， 反应 66.0h， 生成 (6-{[(S)-2-((2R,3R)-2-tert-Butoxycarbonylamino-3-methyl-pentanoylamino)-3-phenyl-propionyl]-[4-(tert-butyl-dimethyl-silanyloxy)-1,1-dioxo-hexahydro-1λ6-thiopyran-3-yl]-amino}-hexyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  A Comparison of Cyclohexanone and Tetrahydro-4H-thiopyran-4-one 1,1-Dioxide as Pharmacophores for the Design of Peptide-Based Inhibitors of the Serine Protease Plasmin

  摘要：

  The plasminogen system is important in the proteolytic cascade that facilitates angiogenesis, a process that is essential for tumor growth and metastasis. The serine protease plasmin has a central role in the plasminogen system. This protease acts by degrading several components of the basement membrane and by activating other proteases. Therefore, inhibition of plasmin may be an effective method for blocking angiogenesis and, as a result, inhibiting the growth of primary tumors and secondary metastases. Three pairs of plasmin inhibitors were synthesized to compare the relative potency of inhibitors that are based upon a cyclohexanone or a tetrahydro-4H-thiopyran-4-one 1,1-dioxide nucleus. Compounds 1, 3, and 5 were cyclohexanone-based inhibitors, whereas compounds 2, 4, and 6 were tetrahydro-4H-thiopyran-4-one 1,1-dioxide-based inhibitors. Compounds 5 and 6 are reasonable inhibitors with IC50 values of 25 and 5.5 mu M, respectively. Comparisons of the IC50 values of the three pairs show that the electron-withdrawing sulfone functional group is a beneficial element for the design of plasmin inhibitors. The presence of the sulfone increases inhibitor potency by a factor of 3-5 when compared to inhibitors that are based upon a simple cyclohexanone core.

  DOI：

  10.1021/jo0508954
• 作为产物：
  描述：

  3,3'-硫代二丙酸二甲酯 在 sodium 、 sodium cyanoborohydride 、 柠檬酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 为溶剂， 反应 0.67h， 生成 (3S,4R)-Methyl 4-hydroxytetrahydro-2H-thiopyran-3-carboxylate
  参考文献：
  名称：

  β-烷氧基对四氢-4H-硫代吡喃-4-酮与4-烷氧基四氢-2H-硫代吡喃-3-甲醛的醛醇缩合反应的非对映选择性的影响。

  摘要：

  在各种条件下，研究了四氢-4H-硫代吡喃-4-酮（3）与1,4-二氧杂-8-硫杂螺[4.5]癸烷-6-甲醛（9a）的醛醇缩合反应的非对映选择性。在最佳条件下，可以选择性地（3-16：1）从该醛醇缩合反应中获得四种可能的非对映异构体中的三种。9a与3的Li，B，Mg（II）和Ti（IV）的烯酸酯以及相应的三甲基甲硅烷基烯醇醚4b在BF（3）x OEt（2），SnCl（4）或TiCl（4）作为促进剂仅以合成的（11a）和反（12a）非对映体混合物形式提供Felkin加合物（> 95％）。与使用由二异丙基氨基锂生成的3烯酸锂（3∶1； 3∶1； 2； 3∶1； 3∶3∶1； 3∶3∶1； 2∶3； 2∶3； 1∶3）相比，使用3的“无胺”烯醇酸锂得到的12a具有更高的非对映选择性（9∶1）和产率（70％）。 15-40％）。TiCl（4）促进4b与9a的反应生成具有出色选择性（16：1）的11a。相比之下，MgBr（2）x

  DOI：

  10.1021/jo016291r

文献信息

• Cyclic sulfone containing retroviral protease inhibitors
  申请人：Bertenshaw E. Deborah

  公开号：US20070015818A1

  公开（公告）日：2007-01-18

  The present invention relates to cyclic sulfone moiety-containing hydroxyethylamine protease inhibitor compounds and pharmaceutical or method of use therefor, particularly as an inhibitor of HIV protease.

  本发明涉及含有环磺酮基团的羟乙基胺蛋白酶抑制剂化合物及其制药或使用方法，特别是作为HIV蛋白酶抑制剂。
• Hoffmann, Reinhard W.; Ladner, Wolfgang; Helbig, Wilfried, Liebigs Annalen der Chemie, 1984, # 6, p. 1170 - 1179
  作者：Hoffmann, Reinhard W.、Ladner, Wolfgang、Helbig, Wilfried

  DOI：——

  日期：——
• Synthesis of Chiral Epoxides from Aldehydes Using Sulfur Ylide Derived from Reduced Product of Bakers' Yeast Reduction
  作者：Ryuuichirou Hayakawa、Makoto Shimizu

  DOI：10.1055/s-1999-2830

  日期：1999.8
• Chiral Auxiliary Mediated Conjugate Reduction and Asymmetric Protonation: Synthesis of High Affinity Ligands for HIV Protease Inhibitors
  作者：Arun K. Ghosh、Wenming Liu

  DOI：10.1021/jo00124a042

  日期：1995.9
• A Comparison of Cyclohexanone and Tetrahydro-4<i>H</i>-thiopyran-4-one 1,1-Dioxide as Pharmacophores for the Design of Peptide-Based Inhibitors of the Serine Protease Plasmin
  作者：Fengtian Xue、Christopher T. Seto

  DOI：10.1021/jo0508954

  日期：2005.10.1

  The plasminogen system is important in the proteolytic cascade that facilitates angiogenesis, a process that is essential for tumor growth and metastasis. The serine protease plasmin has a central role in the plasminogen system. This protease acts by degrading several components of the basement membrane and by activating other proteases. Therefore, inhibition of plasmin may be an effective method for blocking angiogenesis and, as a result, inhibiting the growth of primary tumors and secondary metastases. Three pairs of plasmin inhibitors were synthesized to compare the relative potency of inhibitors that are based upon a cyclohexanone or a tetrahydro-4H-thiopyran-4-one 1,1-dioxide nucleus. Compounds 1, 3, and 5 were cyclohexanone-based inhibitors, whereas compounds 2, 4, and 6 were tetrahydro-4H-thiopyran-4-one 1,1-dioxide-based inhibitors. Compounds 5 and 6 are reasonable inhibitors with IC50 values of 25 and 5.5 mu M, respectively. Comparisons of the IC50 values of the three pairs show that the electron-withdrawing sulfone functional group is a beneficial element for the design of plasmin inhibitors. The presence of the sulfone increases inhibitor potency by a factor of 3-5 when compared to inhibitors that are based upon a simple cyclohexanone core.