5-hydroxy-4-oxo-2-phenyl-4H-1-benzopyran-6,7-diyl diacetate | 731817-58-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 5-hydroxy-4-oxo-2-phenyl-4H-1-benzopyran-6,7-diyl diacetate
• 英文别名: 5-hydroxy-4-oxo-2-phenyl-4H-chromene-6,7-diyl diacetate；5-hydroxy-6,7-diacetoxy-2-phenyl-4H-benzopyran-4-one；6,7-diacetoxy-5-hydroxyflavone；6,7-diacetyl baicalein；(6-Acetyloxy-5-hydroxy-4-oxo-2-phenylchromen-7-yl) acetate
• CAS: 731817-58-6
• 化学式: C₁₉H₁₄O₇
• 分子量: 354.316
• InChiKey: ZECOOWYIOUNSNT-UHFFFAOYSA-N

物化性质

• 熔点：
  194 °C
• 沸点：
  563.9±50.0 °C(Predicted)
• 密度：
  1.400±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  99.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-hydroxy-4-oxo-2-phenyl-4H-1-benzopyran-6,7-diyl diacetate 在 盐酸 、 sodium dithionite 、 水 、 potassium carbonate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.17h， 生成 千层纸素A
  参考文献：
  名称：

  Synthesis of Oroxylin a Starting from Naturally Abundant Baicalin

  摘要：

  A new approach to oroxylin A, a monomethylated trihydroxyflavone, is described. The starting material was baicalin, a representative naturally abundant flavonoid glucuronide. First, conditions for the cleavage of the glycosidic bond were established, using a mixture of water and conc. sulfuric acid (5:2) at 121 degrees C for 40 min. The hydrolysis was performed in a high-pressure steam sterilizer so that the temperature and reaction time were precisely controlled. Subsequent acetylation of the crude material furnished baicalein 6,7-diacetate on a preparative scale and in a reproducible manner Next, the C-7 position was protected site-selectively with a methoxymethyl (MOM) group, taking advantage of an unexpected sequential migration of the two acetyl groups among the C-5, C-6, and C-7 positions under basic conditions. The removal of the two remaining acetyl groups followed by site-selective methylation of the C-6 position furnished 5-hydroxy-6-methoxy-7-methoxymethoxyflavone (oroxylin A C-7 MOM ether). Finally, by the deprotection of the MOM ether, oroxylin A was obtained in 6 total steps and 62% overall yield from baicalin.

  DOI：

  10.3987/com-18-s(t)59
• 作为产物：
  描述：

  黄芩苷 在 硫酸 、 水 、 sodium acetate 作用下， 反应 1.34h， 生成 5,6,7-triacetoxyflavone 、 5-hydroxy-4-oxo-2-phenyl-4H-1-benzopyran-6,7-diyl diacetate
  参考文献：
  名称：

  Synthesis of Oroxylin a Starting from Naturally Abundant Baicalin

  摘要：

  A new approach to oroxylin A, a monomethylated trihydroxyflavone, is described. The starting material was baicalin, a representative naturally abundant flavonoid glucuronide. First, conditions for the cleavage of the glycosidic bond were established, using a mixture of water and conc. sulfuric acid (5:2) at 121 degrees C for 40 min. The hydrolysis was performed in a high-pressure steam sterilizer so that the temperature and reaction time were precisely controlled. Subsequent acetylation of the crude material furnished baicalein 6,7-diacetate on a preparative scale and in a reproducible manner Next, the C-7 position was protected site-selectively with a methoxymethyl (MOM) group, taking advantage of an unexpected sequential migration of the two acetyl groups among the C-5, C-6, and C-7 positions under basic conditions. The removal of the two remaining acetyl groups followed by site-selective methylation of the C-6 position furnished 5-hydroxy-6-methoxy-7-methoxymethoxyflavone (oroxylin A C-7 MOM ether). Finally, by the deprotection of the MOM ether, oroxylin A was obtained in 6 total steps and 62% overall yield from baicalin.

  DOI：

  10.3987/com-18-s(t)59

文献信息

• 一种2-取代苯并吡喃-4-酮类化合物及其应用
  申请人：中国人民解放军第二军医大学

  公开号：CN105669625B

  公开（公告）日：2018-05-25

  本发明涉及医药技术领域，公开了一类具有通式I结构的2‑取代苯并吡喃‑4‑酮类化合物及其在制备抗真菌和协同抗真菌药物中的应用。该类化合物可以与氮唑类抗真菌药物共同使用，可提高耐药菌对氮唑类药物的敏感性，实现逆转耐药作用，产生协同抗真菌作用。
• [EN] COMPOUNDS AND METHODS TO INCREASE ANTI-P-GLYCOPROTEIN ACTIVITY OF BAICALEIN BY ALKYLATION ON THE A RING<br/>[FR] COMPOSES ET METHODES DESTINEES A AUGMENTER L'ACTIVITE ANTI-GLYCOPROTEINE P PAR ALKYLATION SUR LE NOYAU A
  申请人：UNIV YALE

  公开号：WO2005075449A1

  公开（公告）日：2005-08-18

  The present invention is directed to analogs of baicalein according to formula (I): where R5 is H, (CI-C12)alkyl, (C2-C13)acyl, or an optionally substituted phenyl or benzyl group, an acyl group, a C1-C20 alkyl or ether group, a phosphate, diphosphate, triphosphate or phosphodiester group; R6 and R7 are each independently H, (C1-C12)alkyl, (C2-C13)acyl, or an optionally substituted phenyl or benzyl or together form a -OCR1R20- group wherein each of R1 and R2 is independently H, a C1-C3 alkyl group or an optionally substituted phenyl or benzyl group; and R8 is H, OH, an O-acyl group, a C1,-C4 alkyl or alkoxy group, F, Cl, Br or I, or a pharmaceutically acceptable salt thereof, which exhibit anti-P-glycoprotein activity and methods of enhancing the bioavailability of active compounds, especially orally administered compounds, by inhibition of P-glycoprotein 170 (P-gp 170) and/or CYP450 enzyme, especially CYP450 3A4 enzyme. Pharmaceutical compositions based upon these novel derivatives according to the present invention are also described herein.

  本发明涉及根据式(I)的黄芩素类似物：其中R5为H，(C1-C12)烷基，(C2-C13)酰基，或者一个可选择取代的苯基或苄基团，酰基，C1-C20烷基或醚基，磷酸酯，二磷酸酯，三磷酸酯或磷酸二酯基团；R6和R7各自独立地为H，(C1-C12)烷基，(C2-C13)酰基，或者一个可选择取代的苯基或苄基，或者一起形成一个-OCR1R20-基团，其中R1和R2中的每一个独立地为H，C1-C3烷基或可选择取代的苯基或苄基团；以及R8为H，OH，一个O-酰基团，一个C1-C4烷基或烷氧基团，F，Cl，Br或I，或其药学上可接受的盐，具有抗P-糖蛋白活性，并通过抑制P-糖蛋白170 (P-gp 170)和/或CYP450酶，特别是CYP450 3A4酶，来增强活性化合物的生物利用度的方法。根据本发明的这些新颖衍生物基础上的药物组合物也在此描述。
• Convenient Method of Synthesizing Aryloxyalkyl Esters from Phenolic Esters Using Halogenated Alcohols
  作者：Xueyang Jiang、Junting Zhou、Yue Zhou、Haopeng Sun、Jian Xu、Feng Feng、Wei Qu

  DOI：10.3390/molecules23071715

  日期：——

  A facile one-pot synthetic method of building aryloxyalkyl esters was developed using various types of phenolic esters with halogenated alcohols. The ready availability of both starting materials, coupled with the required simple experimental technique, enables the current synthetic method of producing aryloxyalkyl esters in a fast and efficient way. It is noteworthy that acyl transfer was demonstrated

  使用各种类型的酚酸酯与卤代醇开发了一种简便的一锅合成方法来构建芳氧基烷基酯。两种起始材料的现成可用性，再加上所需的简单实验技术，使当前能够以快速有效的方式生产芳氧基烷基酯的合成方法成为可能。值得注意的是，在该反应中证实了酰基转移。
• Synthesis of Ring A-Modified Baicalein Derivatives
  作者：Jun-Fei Wang、Ning Ding、Wei Zhang、Peng Wang、Ying-Xia Li

  DOI：10.1002/hlca.201100162

  日期：2011.12

  Baicalein, an important active constituent of the traditional Chinese herb Scutellaria baicalensis, exhibited antitumor activity and inhibitory activity against P‐gp 170. The syntheses of 25 baicalein derivatives, 2–26 (Table), are described here (Scheme 1). These compounds were systematically modified with O‐alkylation and O‐acylation at HOC(5), HOC(6), and HOC(7), singly or in combination, on

  黄ical素是传统中草药黄cut的重要活性成分，具有抗P-gp 170的抗肿瘤活性和抑制活性。这里描述了25种黄ical素衍生物2 – 26的合成（表1）（方案1）。这些化合物进行了系统的修饰ö烷基化和ö酰化在HO  C（5），HO  C（6），和HO  C（7），单独或组合，在环甲为了评价这样的修改对他们的抑制活性对耐多药的肿瘤细胞系和P-gp的作用的黄芩素170在110的高选择性，高效的烷基化全乙酰化的黄芩素C（7）是关键的区别HO  C（6）和HO 黄芩素的C（7）。
• Increased Anti-P-glycoprotein Activity of Baicalein by Alkylation on the A Ring
  作者：Yashang Lee、Hosup Yeo、Shwu-Huey Liu、Zaoli Jiang、Ruben M. Savizky、David J. Austin、Yung-chi Cheng

  DOI：10.1021/jm049949c

  日期：2004.10.1

  The aqueous extract of Scutellariae baicalensis Georgi has inhibitory activity against P-gp 170, a multiple drug resistant gene product. Baicalein, one of the major flavones, was found to be responsible for this activity. The hydroxyl groups of the A ring of baicalein were systematically alkylated in order to assess the effect of such modifications on the activity against P-gp 170. The impact of the baicalein modifications on activity against the growth of a human nasopharyngeal. cancer cell line KB and its P-gp 170 overexpressing cell line KB/MDR were also examined. The results indicate that alkylation of R5 of baicalein does not have a major impact on the interaction with P-gp 170, whereas alkylation of R6 or R7 alone or both, could enhance the interaction of baicalein with P-gp 170 as well as the amount of intracellular accumulation of vinblastine, a surrogate marker for the activity of P-gp 170 pump of KB/MDR cells. In this case, the optimal linear alkyl functionality is a propyl side chain. These modifications could also alter the activity of compounds inhibiting cell growth. Among the different compounds synthesized, the most potent molecule against P-gp 170 is 5-methoxy-6,7-dipropyloxyflavone (23). Its inhibitory activity against P-gp 170 is approximately 40 times better, based on EC50 (concentration of the compound enhancing 50% of the intracellular vinblastine accumulation in the KB/MDR cells) and 3 times higher, based on A(max) (the intracellular vinblastine accumulation of the KB/MDR cells caused by the compound) as compared to baicalein. Compound 23 is also a more selective inhibitor than baicalein against P-gp 170, because its cytotoxicity is less than that observed for baicalein. The growth inhibitory IC50 of compound 23 against KB and KB/MDR cells are about the same, suggesting that compound 23 is unlikely to be a substrate of P-gp 170 pump. Acetylation of R6, R7 or both could also decrease EC50 and increase A(max). Acetylated compounds are more toxic than baicalein, and their potency against cell growth is compromised by the presence of P-gp 170, suggesting that these compounds are substrates of P-gp 170. Benzylation of R6 or R7 but not both also enhanced anti-P-gp170 activity and potency against cell growth; however, the presence of P-gp 170 in cells did not have an impact on their sensitivity to these molecules, suggesting that the benzylated compounds are inhibitors but not substrates of P-gp 170, and perhaps have a different mechanism of action. In conclusion, the substitutions of R6 and R7 hydroxyl groups by alkoxy groups, acetoxy groups, or benzyloxy groups could yield compounds with different modes of action against P-gp 170 with different mechanisms of action against cell growth.