[(3aS,4S,6R,6aR)-4-(3-carbamoylphenyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy-imidazol-1-ylphosphinic acid | 176597-88-9

• 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: [(3aS,4S,6R,6aR)-4-(3-carbamoylphenyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy-imidazol-1-ylphosphinic acid
• CAS: 176597-88-9
• 化学式: C₁₈H₂₂N₃O₇P
• 分子量: 423.362
• InChiKey: SNMLEAFAWYNIES-QXSJWSMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  135
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [(3aS,4S,6R,6aR)-4-(3-carbamoylphenyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy-imidazol-1-ylphosphinic acid 在 Dowex 50-X₈(H⁺) 作用下， 以 N,N-二甲基甲酰胺-d7 、 水 为溶剂， 反应 206.0h， 生成 NADH
  参考文献：
  名称：

  Chemical Synthesis of Benzamide Adenine Dinucleotide:  Inhibition of Inosine Monophosphate Dehydrogenase (Types I and II)

  摘要：

  Treatment of 3-(2,3-O-isopropylidene-beta-D-ribofuranosyl)benzamide (6) with POCl3 in (EtO)(3)-PO afforded only little phosphorylation product (8, 5%), but the major product was 5'-chlorobenzamide riboside (7, 85%). Reaction of 6 with 2-cyanoethyl N,N-diisopropylchlorophosphoramidite followed by 2-cyanoethanol/tetrazole treatment and oxidation with tert-butyl peroxide gave a 1:1 mixture of the desired 5'-O-bis(2-cyanoethyl) phosphate 9 and the chloro derivative 7. This mixture was treated with methanolic ammonia and partitioned between CHCl3 and water. The 2',3'-O-isopropylidenebenzamide mononucleotide (8) was obtained in 21.2% overall yield from the aqueous layer. Compound 8 was then converted into the corresponding imidazolide 11b which, upon coupling with 2',3'-O-acetonide of AMP, afforded the acetonide of benzamide adenine dinucleotide (15) in 94% yield together with small amounts of symmetrical pyrophosphates P-1, P-2-bis(2',3'-O-isopropylideneadenosin-5'-yl)pyrophosphate(13, 3%) and P-1, P-2-bis(2',3'-O-isopropylidene-3-(carbamoylphenyl)-5'-ribosyl)pyrophosphate (14, 2%). Deprotection of 15 with Dowex 50/H+ in water afforded the desired benzamide adenine dinucleotide (BAD) in 93% yield. BAD inhibits inosine monophosphate dehydrogenase type I (IC50 = 0.78 mu M) and type II (IC50 = 0.88 mu M) with same degree of potency.

  DOI：

  10.1021/jm9601415
• 作为产物：
  描述：

  3-(2,3-O-isopropylidene-β-D-ribofuranosyl)benzamide 在 磷酸三乙酯 、 四乙基溴化铵 、 水 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺-d7 为溶剂， 反应 39.0h， 生成 [(3aS,4S,6R,6aR)-4-(3-carbamoylphenyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy-imidazol-1-ylphosphinic acid
  参考文献：
  名称：

  Chemical Synthesis of Benzamide Adenine Dinucleotide:  Inhibition of Inosine Monophosphate Dehydrogenase (Types I and II)

  摘要：

  Treatment of 3-(2,3-O-isopropylidene-beta-D-ribofuranosyl)benzamide (6) with POCl3 in (EtO)(3)-PO afforded only little phosphorylation product (8, 5%), but the major product was 5'-chlorobenzamide riboside (7, 85%). Reaction of 6 with 2-cyanoethyl N,N-diisopropylchlorophosphoramidite followed by 2-cyanoethanol/tetrazole treatment and oxidation with tert-butyl peroxide gave a 1:1 mixture of the desired 5'-O-bis(2-cyanoethyl) phosphate 9 and the chloro derivative 7. This mixture was treated with methanolic ammonia and partitioned between CHCl3 and water. The 2',3'-O-isopropylidenebenzamide mononucleotide (8) was obtained in 21.2% overall yield from the aqueous layer. Compound 8 was then converted into the corresponding imidazolide 11b which, upon coupling with 2',3'-O-acetonide of AMP, afforded the acetonide of benzamide adenine dinucleotide (15) in 94% yield together with small amounts of symmetrical pyrophosphates P-1, P-2-bis(2',3'-O-isopropylideneadenosin-5'-yl)pyrophosphate(13, 3%) and P-1, P-2-bis(2',3'-O-isopropylidene-3-(carbamoylphenyl)-5'-ribosyl)pyrophosphate (14, 2%). Deprotection of 15 with Dowex 50/H+ in water afforded the desired benzamide adenine dinucleotide (BAD) in 93% yield. BAD inhibits inosine monophosphate dehydrogenase type I (IC50 = 0.78 mu M) and type II (IC50 = 0.88 mu M) with same degree of potency.

  DOI：

  10.1021/jm9601415

文献信息

• Chemical Synthesis of Benzamide Adenine Dinucleotide:  Inhibition of Inosine Monophosphate Dehydrogenase (Types I and II)
  作者：Andrzej Zatorski、Kyoichi A. Watanabe、Stephen F. Carr、Barry M. Goldstein、Krzysztof W. Pankiewicz

  DOI：10.1021/jm9601415

  日期：1996.1.1

  Treatment of 3-(2,3-O-isopropylidene-beta-D-ribofuranosyl)benzamide (6) with POCl3 in (EtO)(3)-PO afforded only little phosphorylation product (8, 5%), but the major product was 5'-chlorobenzamide riboside (7, 85%). Reaction of 6 with 2-cyanoethyl N,N-diisopropylchlorophosphoramidite followed by 2-cyanoethanol/tetrazole treatment and oxidation with tert-butyl peroxide gave a 1:1 mixture of the desired 5'-O-bis(2-cyanoethyl) phosphate 9 and the chloro derivative 7. This mixture was treated with methanolic ammonia and partitioned between CHCl3 and water. The 2',3'-O-isopropylidenebenzamide mononucleotide (8) was obtained in 21.2% overall yield from the aqueous layer. Compound 8 was then converted into the corresponding imidazolide 11b which, upon coupling with 2',3'-O-acetonide of AMP, afforded the acetonide of benzamide adenine dinucleotide (15) in 94% yield together with small amounts of symmetrical pyrophosphates P-1, P-2-bis(2',3'-O-isopropylideneadenosin-5'-yl)pyrophosphate(13, 3%) and P-1, P-2-bis(2',3'-O-isopropylidene-3-(carbamoylphenyl)-5'-ribosyl)pyrophosphate (14, 2%). Deprotection of 15 with Dowex 50/H+ in water afforded the desired benzamide adenine dinucleotide (BAD) in 93% yield. BAD inhibits inosine monophosphate dehydrogenase type I (IC50 = 0.78 mu M) and type II (IC50 = 0.88 mu M) with same degree of potency.