罗波斯塔双黄酮 | 49620-13-5

• 物质功能分类: 有机原料 - 酮类化合物
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 中文名称: 罗波斯塔双黄酮
• 英文名称: robustaflavone
• 英文别名: robustflavone；5,7,5',7'-tetrahydroxy-2'-(4-hydroxy-phenyl)-2,6'-(4-hydroxy-m-phenylene)-bis-chromen-4-one；6-[5-(5,7-dihydroxy-4-oxochromen-2-yl)-2-hydroxyphenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl)chromen-4-one
• CAS: 49620-13-5
• 化学式: C₃₀H₁₈O₁₀
• 分子量: 538.467
• InChiKey: BORWSEZUWHQTOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  40
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  174
• 氢给体数：
  6
• 氢受体数：
  10

制备方法与用途

化学性质
这是一种黄色粉末，能溶解于甲醇、乙醇和DMSO等有机溶剂中。它来源于多种植物，包括翠云草（Selaginella uncinata）、红麸杨叶、鸡毛松的枝叶、薄叶卷柏、中华卷柏、卷柏以及江南卷柏。

反应信息

• 作为产物：
  描述：

  5-羟基-4',7-二甲氧基黄酮 在 sodium hydroxide 、 四(三苯基膦)钯 、 碘 、 thallium(I) acetate 、 三溴化硼 、 potassium carbonate 作用下， 以 二氯甲烷 、 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 罗波斯塔双黄酮
  参考文献：
  名称：

  Total Synthesis of Robustaflavone, a Potential Anti-Hepatitis B Agent

  摘要：

  Robustaflavone, a naturally occurring compound, is an inhibitor of hepatitis B virus replication in vitro. Robustaflavone is a biflavanoid composed of two units of apigenin (5,7,4'-trihydroxyflavone) joined via a biaryl linkage between the g-position of one unit and the 3'-position of the other (I6,II3'-biapigenin). The natural material was isolated from the seed-kernels of Rhus succedanea. To provide ready access to sufficient quantities of material for continued biological studies, as well as to provide a general route for the preparation of structural analogues, a total synthesis of robustaflavone was pursued. The total synthesis was approached by constructing apigenin ethers containing functionalities at the 6- and 3'-positions which could be cross-coupled using transition metal catalysis. Key steps of the synthesis included development of a regioselective iodination of an apigenin derivative at the 6-position. Also key was the formation of an apigenin 3'-boronate using a palladium-catalyzed exchange of the corresponding 3'-iodide with a diboron reagent. Finally, identification of appropriate reaction conditions for Suzuki coupling to form the sterically congested 6-3''' biaryl bond of robustaflavone provided access to the desired biflavanoid system. This work represents the first total synthesis of robustaflavone.

  DOI：

  10.1021/jo981186b
• 作为试剂：
  描述：

  氢溴酸 、 氢碘酸 、 Robustaflavone hexamethyl ether 、 三溴化硼 、 三氯化硼 在 罗波斯塔双黄酮 、 silica gel 作用下， 以 溶剂黄146 、 氯仿 为溶剂， 以crude robustaflavone was obtained in 88.9% yield的产率得到罗波斯塔双黄酮
  参考文献：
  名称：

  Robustaflavone, intermediates and analogues and method for preparation thereof

  摘要：

  本文提供了Robustaflavone、其中间体和类似物的合成方法。该方法涉及构建含有6位和3'位官能团的黄烷酮醚，可以使用过渡金属催化交叉偶联。该方法还涉及开发一种在6位上碘化黄烷酮衍生物的区域选择性碘化方法，使用钯催化将相应的3'位碘化物与二硼试剂交换形成黄烷酮3'硼酸酯。最后，使用Suzuki偶联反应形成Robustaflavone的立体阻碍的6-3'双芳基键，从而获得所需的双黄烷类系统。Robustaflavone中间体和类似物可用于制备其他双黄烷类化合物的类似物，如hinokifavone、rhusflavone和succedaneaflavone。

  公开号：

  US06225481B1

文献信息

• [EN] VIRAL POLYMERASE INHIBITORS<br/>[FR] INHIBITEURS DE POLYMERASE VIRALE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2004065367A1

  公开（公告）日：2004-08-05

  An isomer, enantiomer, diastereoisomer or tautomer of a compound, represented by formula (I): wherein wherein A, B, R2, R3, L, M1, M2, M3, M4, Y1, Y0, Z and Sp are as defined in claim 1, or a salt thereof, as an inhibitor of HCV NS5B polymerase.

  化合物的异构体、对映体、非对映异构体或互变异构体，由式(I)所代表：其中A、B、R2、R3、L、M1、M2、M3、M4、Y1、Y0、Z和Sp如权利要求1中定义，或其盐，作为HCV NS5B聚合酶的抑制剂。
• [EN] HEPATITIS C INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS DE L'HÉPATITE C
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2013026163A1

  公开（公告）日：2013-02-28

  A compound of formula (I) useful for the treatment or prevention of hepatitis C viral infection, (Formula (I)) wherein: X1 and X2 are each independently CRB or N; RB is H, (C1-6)alkyl, (C1-6)haloalkyl, halo. -O-(C1-6)alkyl, NH2, NH(C1-6)alkyl or N((C1-6)alkyl)2; R1 and R2 are each independently (C1-6)alkyl optionally mono- or di-substituted with -O-(C1-6)alkyl, NH2, NH(C1-6)alkyl or N((C1-6)alkyl)2; or R1 and R2, together with the carbon to which they are attached, are linked to form a (C3-7)cycloalkyl group or a 3- to 7-membered heterocyclyl, said cycloalkyl and heterocyclyl being optionally mono- or di-substituted with -(C1-6)alkyl; RA is -C(=O)N(R3)(R4), -C(=O)O(R4), heterocyclyl or heteroaryl, wherein each said heterocyclyl and heteroaryl is optionally substituted 1 to 3 times with R41; R5 and R6 are each independently H or (C1-6)alkyl optionally mono- or di-substituted with -O-(C1-6)alkyl, NH2, NH(C1-6)alkyl or N((C1-6)alkyl)2; or R5 and R6, together with the carbon to which they are attached, are linked to form a (C3-7)cycloalkyl group or a 3- to 7-membered heterocyclyl, said cycloalkyl and heterocyclyl being optionally mono- or di-substituted with -(C1-6)alkyl; and n is 0, 1 or 2.

  一种化合物，其化学式为（I），用于治疗或预防丙型肝炎病毒感染，其中：X1和X2分别独立地为CRB或N；RB为H，（C1-6）烷基，（C1-6）卤代烷基，卤基，-O-（C1-6）烷基，NH2，NH（C1-6）烷基或N（（C1-6）烷基）2；R1和R2分别独立地为（C1-6）烷基，可选择地单取代或双取代为-O-（C1-6）烷基，NH2，NH（C1-6）烷基或N（（C1-6）烷基）2；或者R1和R2与它们连接的碳原子一起形成（C3-7）环烷基或3-至7-成员杂环烷基，所述环烷基和杂环烷基可选择地单取代或双取代为-（C1-6）烷基；RA为-C（=O）N（R3）（R4），-C（=O）O（R4），杂环烷基或杂芳基，其中每个所述杂环烷基和杂芳基可选择地用R41取代1至3次；R5和R6分别独立地为H或（C1-6）烷基，可选择地单取代或双取代为-O-（C1-6）烷基，NH2，NH（C1-6）烷基或N（（C1-6）烷基）2；或者R5和R6与它们连接的碳原子一起形成（C3-7）环烷基或3-至7-成员杂环烷基，所述环烷基和杂环烷基可选择地单取代或双取代为-（C1-6）烷基；n为0、1或2。
• [EN] HEPATITIS C INHIBITOR PEPTIDE ANALOGS<br/>[FR] ANALOGUES PEPTIDIQUES D'INHIBITEURS DE L'HEPATITE C
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2006000085A1

  公开（公告）日：2006-01-05

  The invention relates to compounds of formula (I) wherein R', R2, R3, R4, R5, R6, Y, n and m are as defined herein. The compounds are useful for the treatment and prevention of hepatitis C viral infections in mammals by inhibiting HCV NS3 protease. The invention further relates to azalactone compounds of the formula (III) which can be reacted with an amide anion to produce the compounds of formula (I).

  本发明涉及式(I)的化合物，其中R'，R2，R3，R4，R5，R6，Y，n和m如本文所述定义。这些化合物通过抑制HCV NS3蛋白酶，用于治疗和预防哺乳动物中的丙型肝炎病毒感染。本发明进一步涉及可以与酰胺阴离子反应以产生式(I)化合物的azalactone化合物（III）。
• [EN] HEPATITIS C INHIBITOR DIPEPTIDE ANALOGS<br/>[FR] ANALOGUES DIPEPTIDIQUES D'INHIBITEURS DE L'HEPATITE C
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2006007700A1

  公开（公告）日：2006-01-26

  The present invention relates to compounds of formula (I): wherein R1, R2, R4, n and m are as defined herein and R3 is selected from: (i) -C(O)OR31 wherein R31 is (C1-6)alkyl or aryl, wherein the (C1-6)alkyl is optionally substituted with one to three halogen substituents; (ii) -C(O)NR32R33, wherein R32 and R33 are each independently selected form H, (C1-6)alkyl, and Het; (iii) -SOvR34, wherein v is 1 or 2 and R34 is selected from: (C1-6)alkyl, aryl, Het, and NR32R33 wherein R32 and R33 are as defined above; and (iv) -CO(O)-R35, wherein R35 is selected from (C1-8)alkyl, (C3-7)cycloalkyl-(C1-4)alkyl, aryl, aryl-(C1-6)alkyl, Het and Het-(C1-6)alkyl, each of which are optionally substituted with one or more substituents each independently selected from halo, (C1-6)alkyl, (C3-7)cycloalkyl, aryl, Het, hydroxyl, -O-(C1-6)alkyl, -S-(C1-6)alkyl, -SO-(C1-6)alkyl, -SO2-(C1-6)alkyl, -O-aryl, -S-aryl, -SO-aryl and -SO2-aryl, wherein the aryl portion of the -O-aryl, -S-aryl, -SO-aryl and -SO2-aryl are each optionally substituted with one to five halo substituents. The present invention further relates to pharmaceutical compositions containing the compounds of formula (I) and methods for using these analogs in the treatment of HCV infection.

  本发明涉及以下式(I)的化合物：其中R1、R2、R4、n和m如本文所定义，R3选自：(i)-C(O)OR31，其中R31为(C1-6)烷基或芳基，其中(C1-6)烷基可选择地用一到三个卤素取代基取代；(ii)-C(O)NR32R33，其中R32和R33各自独立地选自H、(C1-6)烷基和Het；(iii)-SOvR34，其中v为1或2，R34选自：(C1-6)烷基、芳基、Het和NR32R33，其中R32和R33如上所定义；和(iv)-CO(O)-R35，其中R35选自(C1-8)烷基、(C3-7)环烷基-(C1-4)烷基、芳基、芳基-(C1-6)烷基、Het和Het-(C1-6)烷基，每种均可选择地用一种或多种取代基取代，每种取代基各自独立地选自卤素、(C1-6)烷基、(C3-7)环烷基、芳基、Het、羟基、-O-(C1-6)烷基、-S-(C1-6)烷基、-SO-(C1-6)烷基、-SO2-(C1-6)烷基、-O-芳基、-S-芳基、-SO-芳基和-SO2-芳基，其中-O-芳基、-S-芳基、-SO-芳基和-SO2-芳基的芳基部分可选择地用一到五个卤素取代基取代。本发明还涉及含有式(I)化合物的药物组合物以及在治疗HCV感染中使用这些类似物的方法。
• [EN] VIRAL POLYMERASE INHIBITORS<br/>[FR] INHIBITEURS DE LA POLYMERASE VIRALE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2005080388A1

  公开（公告）日：2005-09-01

  An enantiomer, diastereoisomer or tautomer of a compound, represented by formula (I): wherein either A or B is nitrogen and the other B or A is C, and the radicals R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are as defined herein, or a salt or ester thereof as viral polymerase inhibitors. The compound is used as an inhibitor of RNA dependent RNA polymerases, particularly those viral polymerases within the Flaviviridae family, more particularly to HCV polymerase.

  一个化合物的对映异构体、顺反异构体或互变异构体，由式(I)表示：其中A或B为氮，另一个为B或A为C，基团R1、R2、R3、R4、R5、R6、R7、R8、R9和R10如本文所定义，或其盐或酯作为病毒聚合酶抑制剂。该化合物用作RNA依赖性RNA聚合酶的抑制剂，特别是用于Flaviviridae家族内的病毒聚合酶，更具体地用于HCV聚合酶。