2,3-methylenedioxy-9,10-dimethoxy-13-ethylprotoberberine chloride | 54260-73-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 原小檗碱生物碱及其衍生物
• 英文名称: 2,3-methylenedioxy-9,10-dimethoxy-13-ethylprotoberberine chloride
• 英文别名: 13-ethylberberine chloride；13-Ethylberberine；5,6-dihydro-2,3-methylenedioxybenzo[a]-9,10-dimethoxy-13-ethyl-benzo[g]quinolizinium chloride；21-Ethyl-16,17-dimethoxy-5,7-dioxa-13-azoniapentacyclo[11.8.0.02,10.04,8.015,20]henicosa-1(13),2,4(8),9,14,16,18,20-octaene;chloride
• CAS: 54260-73-0
• 化学式: C₂₂H₂₂NO₄*Cl
• 分子量: 399.874
• InChiKey: HLJAOZVEVJETCY-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.66
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  40.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,3-methylenedioxy-9,10-dimethoxy-13-ethylprotoberberine chloride 在 aluminum (III) chloride 、 盐酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 5,6-dihydro-2,3-dihydroxybenzo[a]-13-ethyl-9-hydroxy-10-methoxybenzo[g]quinolizinium chloride
  参考文献：
  名称：

  DIBENZO a,g]QUINOLIZINIUM DERIVATIVES AND THE SALTS THEREOF

  摘要：

  公开号：

  EP1140930B1
• 作为产物：
  描述：

  盐酸小檗碱 在 sodium tetrahydroborate 、 potassium carbonate 、 溶剂黄146 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 5.5h， 生成 2,3-methylenedioxy-9,10-dimethoxy-13-ethylprotoberberine chloride
  参考文献：
  名称：

  小ber碱的13个取代衍生物的合成：聚集诱导的发射增强和pH敏感性

  摘要：

  合成并表征了13种羟基，甲基，乙基，苄基和（4-甲基）苄基的5种黄连衍生物。13-羟基小ber碱氯化物由于具有羟基而具有聚集诱导的发射增强（AIEE）特性，有利于通过扩大共轭体系来提高分子的刚性。纯溶液中的光学性质，CH 3 OH / H 2在混合溶液中，对非晶态和结晶态进行了比较研究。通过扫描电子显微镜（SEM）和动态光散射（DLS）方法分别获得了不同水含量（0–90 vol％）的13-羟基小ber碱的聚合物形态和粒径，这为小球状的形成提供了合理的解释。纳米粒子在混合溶液中有利于荧光发射。通过单晶X射线衍射测定13-羟基小ber碱的单晶结构。晶体学数据表明，AIEE现象的主要机理是结合分子平面化的J聚集（头尾偶极子堆叠）的存在。通过DFT进行的计算表明，HOMO-LUMO带隙与实验数据一致。为了进一步探索13-羟基小ber碱的生物医学应用，对其细胞活力和细胞成像性能进行了检测，证明13-

  DOI：

  10.1016/j.jphotochem.2017.01.017

文献信息

• A novel and efficient synthesis of 13-methylprotoberberine alkaloids
  作者：Miyoji Hanaoka、Shuji Yoshida、Chisato Mukai

  DOI：10.1039/c39850001257

  日期：——

  13-Methylberberine (6a), dehydrocorydaline (6b), and corysamine (6c, and their tetrahydro derivatives (9a–c) were efficiently synthesised from the corresponding protoberberines (1) through photochemical electrocyclic reaction of 13-methylene-8, 14-cycloberbines (3).

  通过相应的原小-8碱（1）通过13-亚甲基-8、14-环小bin碱的光化学环化反应，有效地合成了13-甲基小ber碱（6a），脱氢科达林（6b）和corysamine（6c及其四氢衍生物（9a - c）。（3）。
• Chemical transformation of protoberberines. XV. A novel and efficient method for the introduction of alkyl groups on the C-13 position in the protoberberine skeleton.
  作者：Miyoji HANAOKA、Shuji YOSHIDA、Chisato MUKAI

  DOI：10.1248/cpb.37.3264

  日期：——

  The Wittig reaction of 8, 14-cycloberbin-13-ones (4), derived from the corresponding protoberberine alkaloids (2), with methylenetriphenylphosphorane afforded 13-methylene-8, 14-cycloberbines (5). Irradiation of 5 with a 100 W high pressure mercury lamp effected photochemically-induced electrocyclic fission of the aziridine ring to yield 13-methylberberine (1a), dehydrocorydaline (1b), and corysamine (1c) in high yield. Introduction of ethyl and propyl groups on the C-13 position in 2 was also conveniently achieved via photochemical reaction of the corresponding alkylidene derivatives (8 and 9, respectively).

  8, 14-环贝尔本-13-酮（4）通过与甲烯三苯基膦的维蒂格反应，来自相应的原贝尔巴林生物碱（2），得到13-亚甲基-8, 14-环贝尔本（5）。使用100 W高压汞灯对5进行辐照，促进了光化学诱导的电环裂解，生成高产率的13-甲基贝尔巴林（1a）、去氢可可碱（1b）和可可酸（1c）。通过相应烷基烯烃衍生物（8和9）进行光化学反应，还方便地在2的C-13位引入了乙基和丙基取代基。
• Dibenzo[a,g]quinolizinium derivatives and the salts thereof
  申请人：Hanwha Corporation

  公开号：US06028197A1

  公开（公告）日：2000-02-22

  The present invention provides a 5,6-dihydrodibenzo[a,g]quinolizinium derivative and the salts thereof of formula (I) which specifically inhibits the sterol 14-reductase which is involved in the distal pathway of cholesterol biosynthesis, and the use of the compound of formula (I) for treating hypercholesterolaemia or hyperlipidaemia. ##STR1## wherein, R.sup.1 and R.sup.2 which may be the same or different from each other, represent a hydroxy group or an alkoxy group having 1 to 4 carbons or R.sup.1 and R.sup.2 together represent a methylenedioxy group; R.sup.3 represents a hydroxy group or an alkoxy group having 1 to 4 carbons; R.sup.4 represents a hydrogen atom, an alkyl group having 1 to 8 carbons, or an alkenyl group having 3 to 8 carbons; X represents inorganic acid ion, organic acid ion or halide, more particularly, nitrate, sulfate, acetate, tartrate, maleate, succinate, citrate, fumarate, aspartate, salicylate, glycerate, ascorbate, fluoride, chloride, iodide or bromide, Z represents an alkyl group having 5 to 12 carbons, or an alkenyl group having 4 to 6 carbons, a N-benzotriazolyl group, a quinolinyl group, a furyl group, a substituted furyl group, or a radical represented by the formula ##STR2## wherein Z.sup.1, Z.sup.2, Z.sup.3, Z.sup.4 and Z.sup.5 which may be the same or different from each other, represent a hydrogen atom, halogen, an alkyl group having 1 to 5 carbons, a trifluoromethyl group, a phenyl group, a substituted phenyl group, a nitro group, an alkoxy group having 1 to 4 carbons, a methylenedioxy group, a trifluoromethoxy group, a hydroxy group, a benzyloxy group, a phenoxy group, a vinyl group, a benzenesulfonylmethyl group or a methoxycarbonyl group; and A and B which may be the same or different from each other, represent carbon or nitrogen.

  本发明提供了一种5,6-二氢二苯并[a,g]喹啉铵衍生物及其盐，其具有式(I)的结构，特异性地抑制参与胆固醇生物合成远端途径的甾醇14-还原酶，并且利用式(I)化合物治疗高胆固醇血症或高脂血症。其中，R.sup.1和R.sup.2可以相同也可以不同，代表一个具有1到4个碳的羟基或烷氧基，或者R.sup.1和R.sup.2一起代表一个亚甲二氧基基团；R.sup.3代表一个具有1到4个碳的羟基或烷氧基；R.sup.4代表一个氢原子，一个具有1到8个碳的烷基，或一个具有3到8个碳的烯基；X代表无机酸离子、有机酸离子或卤素，更具体地说，是硝酸根离子、硫酸根离子、乙酸根离子、酒石酸根离子、马来酸根离子、琥珀酸根离子、柠檬酸根离子、富马酸根离子、天冬氨酸根离子、水杨酸根离子、甘油酸根离子、抗坏血酸根离子、氟化物、氯化物、碘化物或溴化物；Z代表一个具有5到12个碳的烷基，或一个具有4到6个碳的烯基，一个N-苯并三唑基团，一个喹啉基团，一个呋喃基团，一个取代呋喃基团，或一个由式子所代表的基团。其中，Z.sup.1、Z.sup.2、Z.sup.3、Z.sup.4和Z.sup.5可以相同也可以不同，代表一个氢原子、卤素、一个具有1到5个碳的烷基，三氟甲基基团，苯基，取代苯基，硝基，一个具有1到4个碳的烷氧基，亚甲二氧基基团，三氟甲氧基基团，羟基，苄氧基，苯氧基，乙烯基，苯甲磺酰甲基，或甲氧羰基；A和B可以相同也可以不同，代表碳或氮。
• Berberine Analogues as a Novel Class of the Low-Density-Lipoprotein Receptor Up-Regulators: Synthesis, Structure−Activity Relationships, and Cholesterol-Lowering Efficacy
  作者：Ying-Hong Li、Peng Yang、Wei-Jia Kong、Yan-Xiang Wang、Chang-Qin Hu、Zeng-Yan Zuo、Yue-Ming Wang、Hong Gao、Li-Mei Gao、Yan-Chun Feng、Na-Na Du、Ying Liu、Dan-Qing Song、Jian-Dong Jiang

  DOI：10.1021/jm801157z

  日期：2009.1.22

  Twenty-nine derivatives of berberine (1) or pseudoberberine (2) were designed, semisynthesized, and evaluated for their up-regulatory activity on the low-density-lipoprotein receptor (LDLR) expression. SAR analysis revealed that (i) the methylenedioxy group at the 2- and 3-position is an essential element to keep the activity, (ii) the 7-position quaternary ammonium and planar structure of the compound are activity-required, and (iii) addition of electron-donating groups at the 7- or 13-position reduced the activity. Of the compound I analogues, compound 2 exhibited an increased activity on LDLR expression compared to 1. In the hyperlipidemic rats, compound 2 (100 (mg/kg)/day) reduced blood CHO and LDL-c by 42.6% and 49.4%, respectively, more efficient than I did (p < 0.01 for both). The results were confirmed in the hyperlipidemic mice. LD50 of 2 in mice was over 5000 mg/kg (oral). We consider compound 2 a promising cholesterol-lowering drug candidate.
• HANAOKA, MIYOJI;YOSHIDA, SHUJI;MUKAI, CHISATO, CHEM. AND PHARM. BULL., 37,(1989) N2, C. 3264-3267
  作者：HANAOKA, MIYOJI、YOSHIDA, SHUJI、MUKAI, CHISATO

  DOI：——

  日期：——