1-amino-2,5-anhydro-3,4,6-tri-O-benzoyl-1-deoxy-D-allitol | 137272-74-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-amino-2,5-anhydro-3,4,6-tri-O-benzoyl-1-deoxy-D-allitol
• 英文别名: [(2R,3R,4S,5S)-5-(aminomethyl)-3,4-dibenzoyloxyoxolan-2-yl]methyl benzoate
• CAS: 137272-74-3
• 化学式: C₂₇H₂₅NO₇
• 分子量: 475.498
• InChiKey: HLHPWGNTFMMRBC-UARRHKHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  35
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  114
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-amino-2,5-anhydro-3,4,6-tri-O-benzoyl-1-deoxy-D-allitol 在 4-二甲氨基吡啶 、 sodium methylate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 18.75h， 生成 N-((2S,3R,4S,5R)-3,4-Dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-ylmethyl)-acetamide
  参考文献：
  名称：

  A Convenient Synthesis of 4-Deoxypyrazofurin

  摘要：

  据报道，从 2,5-脱水-3,4 开始，分九步制备了 3-ß-D-呋喃核糖基-1H-吡唑-5-甲酰胺（4-脱氧吡唑呋林，3）（总产率为 21%） ,6-三-O-苯甲酰基-D-异腈(6)并通过丙炔酸甲酯和2,5-脱水-3,4,6-三-O-苄基-1-之间的1,3-偶极环加成反应进行脱氧-1-重氮-D-蒜醇 (4)。

  DOI：

  10.1055/s-1991-26565
• 作为产物：
  描述：

  2,3,5-tri-O-benzoyl-β-D-ribofuranosyl-1-carbonitrile 在 sodium (trifluoroacetoxy)borohydride 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 1-amino-2,5-anhydro-3,4,6-tri-O-benzoyl-1-deoxy-D-allitol
  参考文献：
  名称：

  Methylamine adenine dinucleotide (MAD): a co-factor to turn alcohol dehydrogenases into aldolases

  摘要：

  甲基胺腺嘌呤二核苷酸（MAD）是通过化酶合成从1-乙酰氧基-2,3,5-三-O-苯甲酰-D-核糖经过七个步骤制备的，总产率为15.3%。关键步骤是腺苷酸单磷酸和2,5-去水-1-脱氧-1-苯乙酰胺-6-磷酸-D-阿洛糖之间由碳酰二咪唑（CDI）介导的磷酸酯偶联，随后通过青霉素G酰化酶去除苯乙酰胺基团。MAD辅因子提供了一个适当位置的主要胺基官能团，促进了2-氧代丙酰胺与醛在醇脱氢酶的活性位点内的烯胺醛缩合反应，这应该导致这些立体选择性酶转化为醛酮酶。初步研究未发现马肝醇脱氢酶或酵母醇脱氢酶的任何活性。关键词：醛酮酶，醇脱氢酶，辅因子工程，核苷酸，酰化酶。

  DOI：

  10.1139/v02-074

文献信息

• [EN] CYCLIC DINUCLEOTIDES AS ANTICANCER AGENTS<br/>[FR] DINUCLÉOTIDES CYCLIQUES UTILISÉS EN TANT QU'AGENTS ANTICANCÉREUX
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2019046496A1

  公开（公告）日：2019-03-07

  The present invention is directed to compounds of the formula (I) wherein all substituents are defined herein, as well as pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.

  本发明涉及式(I)的化合物，其中所有取代基在此定义，以及包括本发明化合物的药学上可接受的组合物，以及使用这些组合物治疗各种疾病的方法。
• Synthesis and biochemical evaluation of guanidino-alkyl-ribitol derivatives as nucleoside hydrolase inhibitors
  作者：A. Goeminne、M. McNaughton、G. Bal、G. Surpateanu、P. Van Der Veken、S. De Prol、W. Versées、J. Steyaert、A. Haemers、K. Augustyns

  DOI：10.1016/j.ejmech.2007.03.027

  日期：2008.2

  Nucleoside hydrolase (NH) is a key enzyme in the purine salvage pathway. The purine specificity of the IAG-NH from Trypanosoma vivax is at least in part due to cation-pi-stacking interactions. Guanidinium ions can be involved in cation-pi-stacking interactions, therefore a series of guanidino-alkyl-ribitol derivatives were synthesized in order to examine the binding affinity of these compounds towards the target enzyme. The compounds show moderate to good inhibiting activity towards the IAG-NH from T. vivax. (c) 2007 Elsevier Masson SAS. All rights reserved.
• 1,2,3-Triazolylalkylribitol derivatives as nucleoside hydrolase inhibitors
  作者：A. Goeminne、M. McNaughton、G. Bal、G. Surpateanu、P. Van der Veken、S. De Prol、W. Versées、J. Steyaert、S. Apers、A. Haemers、K. Augustyns

  DOI：10.1016/j.bmcl.2007.02.017

  日期：2007.5

  A range of novel 1,2,3-triazolylalkyiribitol derivatives were synthesized and evaluated as nucleoside hydrolase inhibitors. The most active compound (11a) has low micromolar potency and is structurally diverse from previously reported nucleoside hydrolase inhibitors, which, along with the simplicity of the chemistry involved in its synthesis, makes it a good lead for the further development of novel nucleoside hydrolase inhibitors. (C) 2007 Elsevier Ltd. All rights reserved.
• CYCLIC DINUCLEOTIDES AS ANTICANCER AGENTS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20200270298A1

  公开（公告）日：2020-08-27

  The present invention is directed to compounds of the formula wherein all substituents are defined herein, as well as pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.
• Methylamine adenine dinucleotide (MAD): a co-factor to turn alcohol dehydrogenases into aldolases
  作者：Denis Wahler、Jean-Louis Reymond

  DOI：10.1139/v02-074

  日期：2002.6.1

  Methylamine adenine dinucleotide (MAD) was prepared in seven steps and 15.3% overall yield from 1-acetoxy-2,3,5-tri-O-benzoyl-D-ribose by chemoenzymatic synthesis. The key step was the phosphate–phosphate coupling between adenosine monophosphate and 2,5-anhydro-1-deoxy-1-phenylacetamide-6-phosphate-D-allitol (3) mediated by carbonyl diimidazole (CDI), followed by the removal of the phenylacetamido group by penicillin G acylase. The MAD co-factor provided a primary amine functionality that was suitably positioned to promote the enamine aldolization of 2-oxopropionamide with aldehydes within the active site of alcohol dehydrogenases, which should lead to the transformation of these stereoselective enzymes into aldolases. Preliminary investigations did not reveal any activity with horse liver alcohol dehydrogenase or yeast alcohol dehydrogenase.Key words: aldolases, alcohol dehydrogenases, co-factor enginering, nucleosides, acylases.

  甲基胺腺嘌呤二核苷酸（MAD）是通过化酶合成从1-乙酰氧基-2,3,5-三-O-苯甲酰-D-核糖经过七个步骤制备的，总产率为15.3%。关键步骤是腺苷酸单磷酸和2,5-去水-1-脱氧-1-苯乙酰胺-6-磷酸-D-阿洛糖之间由碳酰二咪唑（CDI）介导的磷酸酯偶联，随后通过青霉素G酰化酶去除苯乙酰胺基团。MAD辅因子提供了一个适当位置的主要胺基官能团，促进了2-氧代丙酰胺与醛在醇脱氢酶的活性位点内的烯胺醛缩合反应，这应该导致这些立体选择性酶转化为醛酮酶。初步研究未发现马肝醇脱氢酶或酵母醇脱氢酶的任何活性。关键词：醛酮酶，醇脱氢酶，辅因子工程，核苷酸，酰化酶。