3-(2,3-O-isopropylidene-β-D-ribofuranosyl)benzamide | 138385-43-0

• 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: 3-(2,3-O-isopropylidene-β-D-ribofuranosyl)benzamide
• 英文别名: 3-[(3aS,4S,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]benzamide
• CAS: 138385-43-0
• 化学式: C₁₅H₁₉NO₅
• 分子量: 293.32
• InChiKey: VWVNADGDHWZWDV-XQHKEYJVSA-N

物化性质

• 沸点：
  476.9±45.0 °C(Predicted)
• 密度：
  1.243±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  91
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(2,3-O-isopropylidene-β-D-ribofuranosyl)benzamide 在 磷酸三乙酯 、 Dowex 50-X₈(H⁺) 、 四乙基溴化铵 、 水 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺-d7 、 水 为溶剂， 反应 245.0h， 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：

  2-(3-溴苯基)-4,4-二甲基-4,5-二氢-1,3-恶唑 在 ammonium hydroxide 、 正丁基锂 、 氯化亚砜 、 三溴化硼 、 对甲苯磺酸 、 碘甲烷 作用下， 以 四氢呋喃 、 硝基甲烷 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 66.5h， 生成 3-(2,3-O-isopropylidene-β-D-ribofuranosyl)benzamide
  参考文献：
  名称：

  用于分析 NAD 相互作用组的化学蛋白质组学方法

  摘要：

  烟酰胺腺嘌呤二核苷酸（NAD +）是一种多功能分子。除了氧化还原代谢之外，NAD +作为翻译后修饰酶的底物也具有同样重要的功能，最大的家族是聚 ADP 核糖聚合酶（PARP，人类有 17 个家族成员）。最近令人惊讶的发现非经典 NAD（NAD +/NADH) 结合蛋白表明 NAD 相互作用组可能比之前想象的要大；然而，用于分析和发现 NAD 结合蛋白的广泛有用的化学工具还不存在。在这里，我们描述了用于询问 NAD 相互作用组的可点击光亲和标记 (PAL) 探针 2- 和 6-ad-BAD 的设计、合成和验证。我们发现 2-ad-BAD 以依赖于 UV 的方式有效地标记 PARP。使用 2- 和 6-ad-BAD 进行的化学蛋白质组学实验鉴定了已知和未知的 NAD + /NADH 结合蛋白。总之，我们的研究展示了 2-ad-BAD 和 6-ad-BAD 作为可点击 PAL NAD 探针的实用性。

  DOI：

  10.1021/jacs.1c01302
• 作为试剂：
  描述：

  2-氰乙基N,N-二异丙基氯亚磷酰胺 在 3-(2,3-O-isopropylidene-β-D-ribofuranosyl)benzamide 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (iPr2N)2PO(CH2)2CN 、 [(3aS,4S,6R,6aR)-4-(3-carbamoylphenyl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methyl bis(2-cyanoethyl) phosphate
  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

• Chemoselective and Diastereoselective Synthesis of <i>C</i> ‐Aryl Nucleoside Analogues by Nickel‐Catalyzed Cross‐Coupling of Furanosyl Acetates with Aryl Iodides
  作者：Yuxi Li、Zheng Wang、Luyang Li、Xiaoying Tian、Feng Shao、Chao Li

  DOI：10.1002/anie.202110391

  日期：2022.1.3

  The facile synthesis of C-aryl nucleoside analogues from readily available furanose acetates and aryl iodides is disclosed. This nickel-catalyzed cross-electrophile coupling showed good functional-group compatibility and excellent β-selectivity. The high chemoselectivity with respect to aryl iodides enabled the efficient preparation of a variety of C-aryl halide furanosides suitable for various po

  公开了从容易获得的呋喃糖乙酸酯和芳基碘化物轻松合成C-芳基核苷类似物。这种镍催化的交叉亲电偶联表现出良好的官能团相容性和优异的β-选择性。对芳基碘化物的高化学选择性使得能够有效制备适用于各种后官能化反应的各种C-芳基卤化物呋喃糖苷。
• The Synthesis and Biological Evaluation of Benzamide Riboside and Its Phosphordiamidates Prodrugs
  作者：Jianning Zhou、Chunyan Tan、Nan Zhang、Jian Fan、Chun Guo、Yuyang Jiang

  DOI：10.1080/10426500701808135

  日期：2008.1.14

  penetration ability of benzamide riboside [BR, (1-β-D-ribofuranosyl) benzene-3-carboxamide], which is a novel C-glycoside analogue of nicotinamide riboside and has excellent cytotoxic activity, we designed and synthesized two phosphordiamidates (1a and 1b) as prodrugs to deliver phosphorylated BR into cells. However, the bioactivity evaluation shows that 1a and 1b have lower biological activity (IC50 > 200 μM

  为了克服耐药性并增强苯甲酰胺核苷[BR, (1-β-D-呋喃核糖基) benzo-3-carboxamide]的膜穿透能力，它是烟酰胺核苷的新型C-糖苷类似物，具有优异的细胞毒性活性，我们设计并合成了两种磷酰胺（1a 和 1b）作为前药，将磷酸化的 BR 递送到细胞中。然而，生物活性评估表明，与 BR 相比，1a 和 1b 具有较低的生物活性（IC50 > 200 μM 和 173 μM，分别）。这可能是因为 1a 和 1b 只能作为 BR 储存形式，因此不能代谢为磷酸化苯甲酰胺核苷。
• Structure‐based design, synthesis and biological evaluation of a <scp>NAD</scp> ⁺ analogue targeting <i>Pseudomonas aeruginosa</i> <scp>NAD</scp> kinase
  作者：Rahila Rahimova、Pauline Nogaret、Valérie Huteau、Muriel Gelin、David A. Clément、Gilles Labesse、Sylvie Pochet、Anne‐Béatrice Blanc‐Potard、Corinne Lionne

  DOI：10.1111/febs.16604

  日期：2023.1

  activity against Staphylococcus aureus. Here, we show that this compound, a di-adenosine derivative, is inactive against the NADK enzyme from the Gram-negative bacteria Pseudomonas aeruginosa (PaNADK). This lack of activity can be explained by the crystal structure of PaNADK, which was determined in complex with NADP+ in this study. Structural analysis led us to design and synthesize a benzamide adenine

  多重耐药性是一个重大的公共卫生问题，需要紧急开发新的抗生素，因此需要确定新的细菌靶标。烟酰胺腺嘌呤二核苷酸激酶 NADK 的活性在迄今为止测试的所有细菌中都是必不可少的，包括许多表现出抗生素耐药性导致当前治疗失败的人类病原体。因此，抑制 NADK 是一种有前途的创新抗菌策略，因为目前市场上还没有针对这种酶的药物。通过基于片段的药物设计方法，我们最近开发了一种 NAD +竞争性 NADK 抑制剂，它显示出体内对金黄色葡萄球菌的活性. 在这里，我们表明该化合物是一种双腺苷衍生物，对来自革兰氏阴性菌铜绿假单胞菌(PaNADK) 的 NADK 酶没有活性。这种缺乏活性可以用 PaNADK 的晶体结构来解释，在本研究中它是在与 NADP +的复合物中确定的。结构分析使我们设计并合成了一种苯甲酰胺腺嘌呤二核苷类似物，对 PaNADK 具有活性。这种新型化合物在体外有效抑制 PaNADK 酶活性，K i为
• The Practical Synthesis of a Methylenebisphosphonate Analogue of Benzamide Adenine Dinucleotide:  Inhibition of Human Inosine Monophosphate Dehydrogenase (Type I and II)
  作者：Krzysztof W. Pankiewicz、Krystyna Lesiak、Andrzej Zatorski、Barry M. Goldstein、Stephen F. Carr、Marek Sochacki、Alokes Majumdar、Michael Seidman、Kyoichi A. Watanabe

  DOI：10.1021/jm960641y

  日期：1997.4.1

  beta-Methylene-BAD (8), a nonhydrolyzable analogue of benzamide adenine dinucleotide (BAD), was synthesized as potential inhibitor of human inosine monophosphate dehydrogenase (IMPDH). Treatment of 2',3'-O-isopropylideneadenosine 5'-methylenebisphosphonate (15) with DCC afforded P-1,P-4-bis(2',3'-O-isopropylideneadenosine) 5'-P-1,P-2:P-3,P-4-dimethylenetetrakisphosphonate (17). This compound was further converted with DCC to an active intermediate 18 which upon reaction with 3-(2',3'-O-isopropylidene-beta-D-ribofuranosyl)benzamide (19) gave, after hydrolysis and deisopropylidenation, the desired beta-methylene-BAD (8) in 95% yield. In a similar manner, treatment of 18 with 2',3'-O-isopropylidenetiazofurin (21) followed by hydrolysis and deprotection afforded beta-methylene-TAD (5) in 91% yield. Compound 8 (IC50 = 0.665 mu M) was found to be a 6-8 times less potent inhibitor of IMPDH than 5 (IC50 = 0.107 mu M) and was almost equally potent against IMPDH type I and type II. Although TAD and beta-methylene-TAD were bound by LADH with the same affinity, the binding affinity of 8 toward LADH (K-i = 333 mu M) was found to be 50-fold lower than that of the parent pyrophosphate 7 (K-i = 6.3 mu M).
• Synthesis and cytotoxic activity of C-glycosidic nicotinamide riboside analogs
  作者：Karsten Krohn、Heidi Heins、Klaus Wielckens

  DOI：10.1021/jm00081a012

  日期：1992.2

  The C-glycosidic nicotinamide riboside analogue (2) was prepared by reaction of ribonolactone 24 with the lithiated oxazoline 19 followed by triethylsilane reduction to 26 and deprotection. Selective phosphorylation to the pseudonucleotide 34 was effected via the isopropylidene compound 33. In contrast to the benzoic acid riboside (28) the benzamide riboside (2) showed extremely high cytotoxicity at nanomolar concentrations to S49.1 lymphoma cells but only slightly increased dexamethasone toxicity.