(2R)-N-(2,3,4,6-tetra-O-pivaloyl-β-D-galactopyranosyl)-2-isopropyl-5,6-didehydro-piperidin-4-one

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R)-N-(2,3,4,6-tetra-O-pivaloyl-β-D-galactopyranosyl)-2-isopropyl-5,6-didehydro-piperidin-4-one
• 英文别名: (2R)-2,3-dihydro-2-propyl-1-(2,3,4,6-tetra-O-pivaloyl-β-D-galactopyranosyl)pyridine-4(1H)-one；[(2R,3S,4S,5R,6R)-3,4,5-tris(2,2-dimethylpropanoyloxy)-6-[(2R)-4-oxo-2-propan-2-yl-2,3-dihydropyridin-1-yl]oxan-2-yl]methyl 2,2-dimethylpropanoate
• 化学式: C₃₄H₅₅NO₁₀
• 分子量: 637.811
• InChiKey: OORXQDCKIQVVBN-PSRUHSIGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  45
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  135
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2,3,4,6-四-O-叔戊酰基-beta-D-吡喃半乳糖胺 在 zinc(II) chloride 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (2R)-N-(2,3,4,6-tetra-O-pivaloyl-β-D-galactopyranosyl)-2-isopropyl-5,6-didehydro-piperidin-4-one
  参考文献：
  名称：

  Palladium-catalysed C–C coupling reactions in the enantioselective synthesis of 2,4-disubstituted 4,5-dehydropiperidines using galactosylamine as a stereodifferentiating auxiliary

  摘要：

  Stereoselective synthesis of enantiomerically pure 2,4-disubstituted piperidine derivatives, which are considered interesting pharmacophoric structures, was achieved starting with a tandem Mannich-Michael reaction sequence on O-pivaloylated N-galactosyl aldimines. Subsequent conversion of the thus formed 2-substituted dehydropiperidinones into the corresponding enol tri-flates was carried out by conjugate hydride addition and trapping the enolate with N,N-bis(trifluoromethanesulfonyl)aniline. Their Suzuki-Miyaura coupling with aryl and heteroaryl boronic acids was performed under, conditions compatible with the carbohydrate structure, in particular, with the sensitive N-glycosidic bond. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2004.11.074

文献信息

• Stereoselective Synthesis of Enantiomerically Pure Piperidine Derivatives byN-Galactosylation of Pyridones
  作者：Ellen Klegraf、Markus Follmann、Dieter Schollmeyer、Horst Kunz

  DOI：10.1002/ejoc.200400169

  日期：2004.8

  Stereoselective desymmetrization of 4-pyridone has been achieved through selective N-galactosylation, activation of the N-(galactosyl)pyridone by O-silylation and immediate addition of Grignard compounds. Chiral piperidine derivatives, e.g. (S)-(+)-coniine and (5S,9S)-(+)-indolozidine 167B, were synthesised in enantiomerically pure form using these highly regio- and stereoselective reactions. After

  4-吡啶酮的立体选择性去对称化已经通过选择性 N-半乳糖基化、通过 O-甲硅烷基化激活 N-（半乳糖基）吡啶酮和立即添加格氏化合物来实现。手性哌啶衍生物，例如 (S)-(+)-coniine 和 (5S,9S)-(+)-indolozidine 167B，使用这些高度区域和立体选择性反应以对映体纯形式合成。在 2-吡啶酮的 N-半乳糖基化和 N-半乳糖基-2-吡啶酮的 O-甲硅烷基化后，格氏化合物的添加以高 1,4-区域选择性和完全非对映选择性进行，以提供 4-取代的 5,6-脱氢- 2-哌啶酮。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
• Enantioselective Syntheses of 2-Alkyl-, 2,6-Dialkylpiperidines and Indolizidine Alkaloids Through Diastereoselective Mannich-Michael Reactions
  作者：Markus Weymann、Waldemar Pfrengle、Dieter Schollmeyer、Horst Kunz

  DOI：10.1055/s-1997-3185

  日期：1997.10

  Aldimines of 2,3,4,6-tetra-0-pivaloyl-β-D-galactosylamine react with 1-methoxy-3-trimethylsilyloxybuta-1,3-diene in a Mannich-Michael condensation reaction sequence to give 2-substituted N-galactosyl-5,6-dehydropiperidin-4-ones 3 with high diastereoselectivity. The X-ray analysis of the 2-propyl derivative 3a proved (R)-configuration of the major diastereomer and led to the correction of our earlier assignment of configuration for (-)-coniine hydrochloride 9a obtained from this intermediate. Despite their low reactivity, these enaminones 3 can be converted into chiral 2,6-cis-disubstituted piperidinones 12 with high stereoselectivity by reaction with organocuprates in combination with hard electrophiles. Enantiomerically pure alkaloids such as (-)-dihydropinidine and gephyrotoxine 167B have been synthesized according to this methodology.

  2,3,4,6-四-O-特戊酰基-β-D-半乳糖胺的烯胺与1-甲氧基-3-三甲基硅氧基丁-1,3-二烯在曼尼希-迈克尔缩合反应序列中反应，以高非对映选择性得到2-取代的N-半乳糖基-5,6-脱氢哌啶-4-酮3。2-丙基衍生物3a的X射线分析证实了主要非对映异构体的(R)构型，并纠正了我们之前对该中间体得到的(-)-毒芹碱盐酸盐9a的构型分配。尽管这些烯胺酮3的反应性较低，但通过与有机铜酸盐和硬亲电试剂的反应，可以高立体选择性地将其转化为手性的2,6-顺式-二取代哌啶酮12。根据这一方法，已经合成了高对映纯度的生物碱，如(-)-二氢矮牵牛素和gephyrotoxine 167B。
• Palladium-catalysed C–C coupling reactions in the enantioselective synthesis of 2,4-disubstituted 4,5-dehydropiperidines using galactosylamine as a stereodifferentiating auxiliary
  作者：Stephan Knauer、Horst Kunz

  DOI：10.1016/j.tetasy.2004.11.074

  日期：2005.1

  Stereoselective synthesis of enantiomerically pure 2,4-disubstituted piperidine derivatives, which are considered interesting pharmacophoric structures, was achieved starting with a tandem Mannich-Michael reaction sequence on O-pivaloylated N-galactosyl aldimines. Subsequent conversion of the thus formed 2-substituted dehydropiperidinones into the corresponding enol tri-flates was carried out by conjugate hydride addition and trapping the enolate with N,N-bis(trifluoromethanesulfonyl)aniline. Their Suzuki-Miyaura coupling with aryl and heteroaryl boronic acids was performed under, conditions compatible with the carbohydrate structure, in particular, with the sensitive N-glycosidic bond. (C) 2004 Elsevier Ltd. All rights reserved.