2,3,4,6-tetra-O-benzyl-D-galactothionolactam | 214784-10-8

• 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: 2,3,4,6-tetra-O-benzyl-D-galactothionolactam
• 英文别名: (3R,4S,5S,6R)-3,4,5-tris(phenylmethoxy)-6-(phenylmethoxymethyl)piperidine-2-thione
• CAS: 214784-10-8
• 化学式: C₃₄H₃₅NO₄S
• 分子量: 553.722
• InChiKey: PCPZQSDXDXNPSK-JDIHBLRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  40
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  81
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,3,4,6-tetra-O-benzyl-D-galactothionolactam 在 palladium on activated charcoal 、 氢气 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 36.0h， 生成 N-2-methylbenzyl-D-galactonoamidine
  参考文献：
  名称：

  N-Benzylgalactonoamidines as potent β-galactosidase inhibitors

  摘要：

  A series of N-benzylgalactonoamidines was synthesized to probe their inhibitory ability during the hydrolysis of o-nitrophenyl-beta-D-galactopyranoside by beta-galactosidase (Aspergillus oryzae). All compounds are characterized as potent competitive inhibitors with inhibition constants (K-i) in the low nanomolar range (12-48 nM). The structure of the inhibitors mimics the bond-lengthening during the hydrolysis and the aromatic aglycon of the substrate. The electronic nature of the substituent in p-position of the aglycon influences the overall inhibitory ability most when compared to the unsubstituted parent compound. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.10.048
• 作为产物：
  描述：

  (3R,4S,5S,6R)-3,4,5-tris(benzyloxy)-6-((benzyloxy)methyl)piperidin-2-one 在 劳森试剂 作用下， 以 苯 为溶剂， 反应 2.0h， 以93%的产率得到2,3,4,6-tetra-O-benzyl-D-galactothionolactam
  参考文献：
  名称：

  大体积和极性大半乳糖脒的溶剂控制合成

  摘要：

  本研究的目的是设计和合成大块和极性大的半乳糖脒，它们有可能与人 α-半乳糖苷酶活性位点中的两种催化氨基酸相互作用。虽然先前按照既定方案合成了超过 25 种化合物的库，但所选胺与活化的过苄基化半乳糖硫内酰胺的偶联对于一些过苄基化目标仅产生少量。一种计算方法揭示了选定加合物的相对能量差异，并建议改变溶剂，然后成功合成 20-75% 的前体化合物。随后尝试通过 Pd 催化氢化对过苄基化半乳糖脒进行全局脱保护，导致不需要的 Pd 配位、不完全脱苄基化反应、部分化合物水解、甚至完全分解。在修改去苄基化条件后，制定了一个冗长的协议来纯化目标碳水化合物衍生物。

  DOI：

  10.1016/j.carres.2022.108520

文献信息

• Inhibition of Glycosidases by Lactam Oximes: Influence of the Aglycon in Disaccharide Analogues
  作者：Stefan Vonhoff、Tom D. Heightman、Andrea Vasella

  DOI：10.1002/(sici)1522-2675(19980909)81:9<1710::aid-hlca1710>3.0.co;2-i

  日期：1998.9.9
• Structure–Activity Relationship of Highly Potent Galactonoamidine Inhibitors toward β-Galactosidase (<i>Aspergillus oryzae</i>)
  作者：Qiu-Hua Fan、Kailey A. Claunch、Susanne Striegler

  DOI：10.1021/jm501111y

  日期：2014.11.13

  A small library of 22 N-substituted galactonoamidines was synthesized, and their structure-activity relationship for inhibition of the hydrolytic activity of beta-galactosidase (Aspergillus oryzae) was evaluated. A fast screening assay in 96-well plate format was used to follow the enzymatic hydrolysis of 2-chloro-4-nitrophenyl-beta-d-galactopyranoside using UV-vis spectroscopy. The aglycon moiety of all compounds was found to have a profound effect on their inhibitory ability. In general, galactonoamidines derived from cyclic aliphatic and linear amines show higher inhibition activity than those derived from benzylamines. Hydrophobic interactions of the methyl group rather than pi-pi stacking interactions of the aromatic ring in p-methylbenzyl-d-galactonoamidine were identified to cause its transition-state-like character and the remarkably high inhibitory ability (K-i = 8 nM). A flexible 3-carbon methylene spacer between the exo N atom of the sugar moiety and a phenyl group furthermore increased the observed apparent inhibition drastically
• Multi gram-scale synthesis of galactothionolactam and its transformation into a galactonoamidine
  作者：Rami Kanso、Susanne Striegler

  DOI：10.1016/j.carres.2011.02.021

  日期：2011.5

  We recently proposed to conduct selective glycosylation reactions after in situ activation of a glycosyl donor promoted by a transition metal complex immobilized in a macromolecular matrix. In order to develop this catalytic entity, a feasible multi gram-scale synthesis for 2,3,4,6-tetra-O-benzyl-D-galactothionolactam, its transformation into galactonoamidines with aromatic aglycon, and subsequent debenzylation conditions were developed. The potential for epimerization reactions at C-2 of the glycosidic ring during the transformations from the 2,3,4,6-tetra-O-benzyl-o-galactonolactam into the N-benzy1-2,3,4,6-tetra-O-benzyl-D-galactonoamidines via the 2,3,4,6-tetra-O-benzyl-D-galactothionolactam are discussed and additionally characterized by using density functional theory calculations. (C) 2011 Elsevier Ltd. All rights reserved.