纯绿青霉素醇 | 14484-44-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 纯绿青霉素醇
• 英文名称: viridicatol
• 英文别名: 3-hydroxy-4-(3-hydroxyphenyl)quinolin-2(1H)-one；3-hydroxy-4-(3-hydroxyphenyl)-1H-quinolin-2-one
• CAS: 14484-44-7
• 化学式: C₁₅H₁₁NO₃
• 分子量: 253.257
• InChiKey: QIJIOTTYIGBOQA-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMF：可溶； DMSO：可溶；乙醇：可溶；甲醇：可溶

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  69.6
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 包装等级：
  III
• 危险类别：
  6.1
• 危险性防范说明：
  P261,P264,P270,P271,P280,P302+P352,P304+P340,P310,P330,P361,P403+P233,P405,P501
• 危险品运输编号：
  2811
• 危险性描述：
  H301,H311,H331

制备方法与用途

生物活性方面，viridicatol 是一种从夹竹桃内生真菌青霉菌属的发酵产物中分离出的喹诺酮类生物碱。研究显示，viridicatol 对金黄色葡萄球菌具有很强的抗真菌活性，其最低抑菌浓度（MIC）为 15.6 μg/mL。

反应信息

• 作为反应物：
  描述：

  纯绿青霉素醇 、 三甲基硅烷化重氮甲烷 以 N,N-dimethyl-d₆-formamide 为溶剂， 反应 3.0h， 生成 2,3-dimethoxy-4-(3-methoxyphenyl)quinoline
  参考文献：
  名称：

  A new quinolinone and its natural/artificial derivatives from a shark gill-derived fungus Penicillium polonicum AP2T1

  摘要：

  Four quinolinones (1-4; 1 is a new compound) were isolated from the static fermentation culture of a shark gill-derived fungus Penicillium polonicum AP2T1. In addition, five new quinolinone derivatives (5-9) and also 1 were obtained in a trimethylsilyldiazomethane-induced methylation reaction of 4. Their structures were elucidated by spectroscopic analyses. In bioassays, compounds 7 and 5 with lactim structures moderately inhibited the proliferation of human cancer cell line HCT116 (wild-type) with IC50-24 h of 8.4 mu g/mL and 30.7 mu g/mL, respectively; the other compounds displayed weaker inhibition. The p53 gene may play some role in their action as suggested by their much weakened activity towards p53-knockout HCT116 cell line. Besides, 6 and 8 exhibited moderate or weak toxicity to brine shrimp larvae, and 3, 4, 8 and 9 showed weak inhibition against Staphylococcus aureus. It is the first report on elucidation of new compounds with origin of shark-derived fungi.

  DOI：

  10.1080/14786419.2015.1045906
• 作为产物：
  描述：

  在 硫酸 、 sodium nitrite 作用下， 以 四氢呋喃 、 水 为溶剂， 以98%的产率得到纯绿青霉素醇
  参考文献：
  名称：

  通过Darzens缩合/ Friedel-Crafts烷基化策略合成包括羟基吡啶的3-羟基-4-芳基喹啉-2-酮

  摘要：

  描述了一种新的有效的生物重要的3-羟基-4-芳基喹啉-2-酮的有效合成方法，该方法是通过二氯乙苯胺与芳族醛的Darzens缩合（环氧化），然后进行一锅式脱氯环氧-芳烃环化。该方法已用于合成天然存在的维地卡多，这是一种从青霉菌属中分离出来的真菌代谢产物。

  DOI：

  10.1021/acs.joc.8b01871

文献信息

• Regioselective Ring Expansion of Isatins with <i>In Situ</i> Generated α-Aryldiazomethanes: Direct Access to Viridicatin Alkaloids
  作者：Yellaiah Tangella、Kesari Lakshmi Manasa、Namballa Hari Krishna、B. Sridhar、Ahmed Kamal、Bathini Nagendra Babu

  DOI：10.1021/acs.orglett.8b01417

  日期：2018.6.15

  A novel efficient one-pot regioselective ring-expansion reaction of isatins with in situ generated α-aryl/heteroaryldiazomethanes for the construction of viridicatin alkaloids has been described under metal-free conditions. The utility of this protocol is further demonstrated in the synthesis of naturally occurring viridicatin, viridicatol, and substituted 3-O-methyl viridicatin and their scale up

  在无金属条件下，已经描述了一种新型的靛红与原位生成的α-芳基/杂芳基重氮甲烷的有效的一锅区域选择性环扩环反应，用于构建ridicatin的生物碱。该协议的效用在天然存在的viridicatin，viridicatol和取代的3- O-甲基viridicatin的合成及其规模放大中得到了进一步证明。
• Scalable total synthesis of aflaquinolone I and confirmation of the absolute configuration
  作者：Feng-Wei Guo、Yang Gao、Yu-Cheng Gu、Chang-Lun Shao

  DOI：10.1016/j.tet.2023.133299

  日期：2023.3

  α-hydroxyanilide and a diastereoselective aldol cyclization to construct the 3,4-dioxygenated-4-aryl-quinolin-2(1H)-one core. The second approach included a regioselective insertion of aryne into unsymmetric imide to build the N-glycolated 2-amino-benzophenone as a key step. In addition, the dehydrated product of aflaquinolone I, viridicatol (2), was successfully synthesized. We also achieved the chiral resolution

  黄喹诺酮 I ( 1 )的首次全合成，它代表了天然存在的 3,4-二氧化 4-芳基喹啉-2(1 H )-一种具有 3 R和 4 R配置的生物碱的第一个实例，于 9 年实现和 4 个步骤，分别采用两种并行策略。第一种方法的关键步骤包括碱催化偶联反应以形成α-羟基苯胺和非对映选择性羟醛环化以构建 3,4-二氧化-4-芳基-喹啉-2(1 H )-一核。第二种方法包括将芳炔区域选择性地插入不对称酰亚胺中以构建N-glycolated 2-amino-benzophenone 作为关键步骤。此外，还成功合成了黄喹诺酮 I 的脱水产物 viridicatol ( 2 )。我们还使用手性色谱实现了 (±)-黄喹诺酮 I ( 1 ) 和 (±)- 20的手性拆分，并通过电子圆二色性 (ECD) 确定了对映体的绝对构型。进一步证实了黄喹诺酮Ⅰ的绝对构型。有趣的是，我们发现黄喹诺酮 I 及其相关类似物的 ECD
• A Concise and Versatile Synthesis of Viridicatin Alkaloids from Cyanoacetanilides
  作者：Yusuke Kobayashi、Takashi Harayama

  DOI：10.1021/ol900255g

  日期：2009.4.2

  The efficient synthesis of 3-hydroxy-4-arylquinolin-2(1H)-ones through one-pot Knoevenagel condensation/epoxidation of cyanoacetanilides followed by decyanative epoxide-arene cyclization is described. A convergent assembly with functionalized aldehydes allows for rapid synthesis with diverse substitution patterns. Isolation of 3-hydroxy-4-arylquinolin-2(1H)-ones is readily accomplished by precipitation and filtration.
• Synthesis of 3-Hydroxy-4-arylquinolin-2-ones Including Viridicatol via a Darzens Condensation/Friedel–Crafts Alkylation Strategy
  作者：Vakhid A. Mamedov、Vera L. Mamedova、Saniya F. Kadyrova、Venera R. Galimullina、Gul’naz Z. Khikmatova、Dmitry E. Korshin、Aidar T. Gubaidullin、Dmitry B. Krivolapov、Il’dar Kh. Rizvanov、Olga B. Bazanova、Oleg G. Sinyashin、Shamil K. Latypov

  DOI：10.1021/acs.joc.8b01871

  日期：2018.11.2

  The new efficient synthesis of biologically important 3-hydroxy-4-arylquinolin-2-ones through the Darzens condensation (epoxidation) of dichloroacetanilides with aromatic aldehydes followed by one-pot dechlorative epoxide-arene cyclization is described. This methodology has been utilized for the synthesis of naturally occurring viridicatol, a fungal metabolite isolated from the penicillium species

  描述了一种新的有效的生物重要的3-羟基-4-芳基喹啉-2-酮的有效合成方法，该方法是通过二氯乙苯胺与芳族醛的Darzens缩合（环氧化），然后进行一锅式脱氯环氧-芳烃环化。该方法已用于合成天然存在的维地卡多，这是一种从青霉菌属中分离出来的真菌代谢产物。
• A new quinolinone and its natural/artificial derivatives from a shark gill-derived fungus <i>Penicillium polonicum</i> AP2T1
  作者：Yi Zhang、Jun Mu、Frank Essmann、Yan Feng、Markus Kramer、Hai-yan Bao、Stephanie Grond

  DOI：10.1080/14786419.2015.1045906

  日期：2017.5.3

  Four quinolinones (1-4; 1 is a new compound) were isolated from the static fermentation culture of a shark gill-derived fungus Penicillium polonicum AP2T1. In addition, five new quinolinone derivatives (5-9) and also 1 were obtained in a trimethylsilyldiazomethane-induced methylation reaction of 4. Their structures were elucidated by spectroscopic analyses. In bioassays, compounds 7 and 5 with lactim structures moderately inhibited the proliferation of human cancer cell line HCT116 (wild-type) with IC50-24 h of 8.4 mu g/mL and 30.7 mu g/mL, respectively; the other compounds displayed weaker inhibition. The p53 gene may play some role in their action as suggested by their much weakened activity towards p53-knockout HCT116 cell line. Besides, 6 and 8 exhibited moderate or weak toxicity to brine shrimp larvae, and 3, 4, 8 and 9 showed weak inhibition against Staphylococcus aureus. It is the first report on elucidation of new compounds with origin of shark-derived fungi.