N-tosyl-D-pipecolic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-tosyl-D-pipecolic acid
• 英文别名: (R)-N-tosylpipecolic acid；(R)-piperidine-2-carboxylic acid；(2R)-1-(4-methylphenyl)sulfonylpiperidine-2-carboxylic acid
• 化学式: C₁₃H₁₇NO₄S
• mdl: MFCD23224218
• 分子量: 283.348
• InChiKey: GCWLCINIEOOJGU-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.461
• 拓扑面积：
  83.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-tosyl-D-pipecolic acid 在 potassium phosphate 、 palladium diacetate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2R)-N-[5-(1-benzofuran-5-yl)-1,3-thiazol-2-yl]-1-(4-methylphenyl)sulfonylpiperidine-2-carboxamide
  参考文献：
  名称：

  Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide, ML277, as a novel, potent and selective Kv7.1 (KCNQ1) potassium channel activator

  摘要：

  A high-throughput screen utilizing a depolarization-triggered thallium influx through KCNQ1 channels was developed and used to screen the MLSMR collection of over 300,000 compounds. An iterative medicinal chemistry approach was initiated and from this effort, ML277 was identified as a potent activator of KCNQ1 channels (EC50 = 260 nM). ML277 was shown to be highly selective against other KCNQ channels (> 100-fold selectivity versus KCNQ2 and KCNQ4) as well as against the distantly related hERG potassium channel. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.07.060
• 作为产物：
  描述：

  (4E)-4-[3-(4-methylphenyl)sulfonyl-2-oxo-1,3-oxazolidin-4-ylidene]butanal 在 (S)-(+)-5,5'-双[二(3,5-二叔丁基-4-甲氧基苯基)膦]-4,4'-二-1,3-苯并二氧戊环 、 chloro(1,5-cyclooctadiene)rhodium(I) dimer lithium hydroxide 、 jones' reagent 、 氢气 、 sodium hydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 乙醇 、 水 、 丙酮 、 甲苯 为溶剂， 30.0 ℃ 、6.08 MPa 条件下， 反应 190.0h， 生成 N-tosyl-D-pipecolic acid
  参考文献：
  名称：

  中性铑配合物催化N-甲苯磺恶唑烷酮类化合物环外双键的高对映选择性加氢反应及其合成应用

  摘要：

  光学活性的对映体选择性高的合成Ñ基于所述三取代的环外双键的不对称氢化甲苯磺酰基-4-烷基-1,3-恶唑烷-2-酮Ñ甲苯磺酰基-4-亚烷基-1,3-恶唑烷在中性[Rh（COD）Cl] 2（COD = 1,5-环辛二烯）和（S）-（+）-DTBM-SEGPHOS的催化下，开发了2-ones。通过合成旋光氨基酸，氨基醇和哌啶衍生物来举例说明这种高对映选择性反应的效用。

  DOI：

  10.1016/j.tet.2006.07.024

文献信息

• Complementary routes to both enantiomers of pipecolic acid and 4,5-dihydroxypipecolic acid derivatives
  作者：Shital K. Chattopadhyay、Titas Biswas、Tanmoy Biswas

  DOI：10.1016/j.tetlet.2007.12.097

  日期：2008.2

  Complementary new routes to both enantiomers of N-protected pipecolic acid and the corresponding 4,5-dihydroxylated derivatives are developed, which involve stereo-divergent allylation of a chiral N-allylimine and ring-closing metathesis as key steps.

  已开发出同时获得N-保护的胡椒酸对映异构体和相应的4,5-二羟基化衍生物的互补新途径，其中涉及手性N-烯丙胺的立体发散烯丙基化和闭环易位作为关键步骤。
• Highly enantioselective hydrogenation of exocyclic double bond of N-tosyloxazolidinones catalyzed by a neutral rhodium complex and its synthetic applications
  作者：Zengming Shen、Xiyan Lu、Aiwen Lei

  DOI：10.1016/j.tet.2006.07.024

  日期：2006.9

  A highly enantioselective synthesis of optically active N-tosyl-4-alkyl-1,3-oxazolidin-2-ones based on the asymmetric hydrogenation of the trisubstituted exocyclic double bond of N-tosyl-4-alkylidene-1,3-oxazolidin-2-ones under the catalysis of neutral [Rh(COD)Cl]2 (COD=1,5-cyclooctadiene) and (S)-(+)-DTBM-SEGPHOS was developed. The utility of this highly enantioselective reaction was exemplified by

  光学活性的对映体选择性高的合成Ñ基于所述三取代的环外双键的不对称氢化甲苯磺酰基-4-烷基-1,3-恶唑烷-2-酮Ñ甲苯磺酰基-4-亚烷基-1,3-恶唑烷在中性[Rh（COD）Cl] 2（COD = 1,5-环辛二烯）和（S）-（+）-DTBM-SEGPHOS的催化下，开发了2-ones。通过合成旋光氨基酸，氨基醇和哌啶衍生物来举例说明这种高对映选择性反应的效用。
• Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide, ML277, as a novel, potent and selective Kv7.1 (KCNQ1) potassium channel activator
  作者：Margrith E. Mattmann、Haibo Yu、Zhihong Lin、Kaiping Xu、Xiaofang Huang、Shunyou Long、Meng Wu、Owen B. McManus、Darren W. Engers、Uyen M. Le、Min Li、Craig W. Lindsley、Corey R. Hopkins

  DOI：10.1016/j.bmcl.2012.07.060

  日期：2012.9

  A high-throughput screen utilizing a depolarization-triggered thallium influx through KCNQ1 channels was developed and used to screen the MLSMR collection of over 300,000 compounds. An iterative medicinal chemistry approach was initiated and from this effort, ML277 was identified as a potent activator of KCNQ1 channels (EC50 = 260 nM). ML277 was shown to be highly selective against other KCNQ channels (> 100-fold selectivity versus KCNQ2 and KCNQ4) as well as against the distantly related hERG potassium channel. (C) 2012 Elsevier Ltd. All rights reserved.