methyl 3,3-dihydroperoxy-7α,12α-diacetoxy-5β-cholan-24-oate | 452302-69-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: methyl 3,3-dihydroperoxy-7α,12α-diacetoxy-5β-cholan-24-oate
• 英文别名: methyl (4R)-4-[(5R,7R,8R,9S,10S,12S,13R,14S,17R)-7,12-diacetyloxy-3,3-dihydroperoxy-10,13-dimethyl-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]pentanoate
• CAS: 452302-69-1
• 化学式: C₂₉H₄₆O₁₀
• 分子量: 554.678
• InChiKey: UQLUDCJFAVIJPH-TVAYOAIPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  138
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  methyl 3,3-dihydroperoxy-7α,12α-diacetoxy-5β-cholan-24-oate 在 sodium hydroxide 、 硫酸 、 potassium carbonate 、 乙腈 作用下， 以 二氯甲烷 、 水 、 异丙醇 为溶剂， 反应 3.0h， 生成 7α,12α-diacetoxy-5β-cholan-24-oic acid 3-spiro-6'-(1',2',4',5'-tetraoxacyclohexane)-3'-spiro-1''-((4''R)-carboxy)cyclohexane
  参考文献：
  名称：

  Tetraoxane Antimalarials and Their Reaction with Fe(II)

  摘要：

  Mixed tetraoxanes 5a and 13 synthesized from cholic acid and 4-oxocyclohexanecarboxylic acid were as active as artemisinin against chloroquine-susceptible, chloroquine-resistant, and multidrug-resistant Plasmodium falciparum strains (IC50, IC90). Most active 13 is metabolically stable in in vitro metabolism studies. In vivo studies on tetraoxanes with a C(4'') methyl group afforded compound 15, which cured 4/5 mice at 600 and 200 mg, kg(-1), day(-1), and 2/5 mice at 50 mg, kg(-1), day(-1), showing no toxic effects. Tetraoxane 19 was an extremely active antiproliferative with LC50 of 17 nM and maximum tolerated dose of 400 mg/kg. In Fe(II)-induced scission of tetraoxane antimalarials only RO center dot radicals were detected by EPR experiments. This finding and the indication of Fe(IV)=O species led us to propose that RO center dot radicals are probably capable of inducing the parasite's death. Our results suggest that C radicals are possibly not the only lethal species derived from peroxide prodrug antimalarials, as currently believed.

  DOI：

  10.1021/jm050966r
• 作为产物：
  描述：

  methyl 3-keto-7,12-diacetylcholate 在 盐酸 、 双氧水 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 生成 methyl 3,3-dihydroperoxy-7α,12α-diacetoxy-5β-cholan-24-oate
  参考文献：
  名称：

  Elicitation effects of synthetic 1,2,4,5-tetraoxane and 2,5-diphenyltiophene in shoot cultures of two Nepeta species

  摘要：

  本研究的目的是调查 Nepeta cataria L. 和 N. pannonica 主要次生代谢物产生的可能性。 L. 植物中主要次生代谢物产生的可能性。 四氧杂环己烷和噻吩类合成化合物。DO63（1,2,4,5-四氧杂环戊烷）和 DOVF15（2,5-二苯基噻吩）对顺式、反式庚内酯（NL）和迷迭香内酯（RL）生产的影响。 (和迷迭香酸（RA）的影响进行了研究。 在培养基上生长的嫩枝中，加入浓度为 浓度范围为 0.1 至 2 mg L-1。目标 代谢物的含量取决于所使用合成化合物的类型和浓度。 浓度而定。施用 DO63，主要是 浓度为 0.1 毫克/升-1 至 1 毫克/升-1 的 DO63 只影响 NL 的产生。 这两种植物的 NL 产量，结果是处理后的嫩芽中 NL 含量增加、 而 RA 的产生则不受影响。添加 DOVF15 会导致 pannonica 嫩芽中的 RA 含量降低，而 N. cataria 嫩芽中的 RA 含量降低，而 N. cataria 嫩芽中的 RA 含量增加，而 NL 产量未受影响。以上结果 结果表明，DO63 和 DOVF15 有可能诱导 的可能性。 Nepeta。

  DOI：

  10.2298/jsc160226054d

文献信息

• Mixed steroidal 1, 2, 4, 5- tetraoxane compounds and methods of making and using thereof
  申请人：——

  公开号：US20040019200A1

  公开（公告）日：2004-01-29

  Disclosed herein are mixed steroidal tetraoxanes having the following structural formula 1 1 wherein n is 0, 1, 2, or 3; R is H; ethanoyl, propanoyl, or benzoyl; R1 is H, methyl, ethyl, or isopropyl; R2 is H, methyl, or ethyl; R3 is H, methyl, or ethyl; R4 is H, methyl, ethyl, tert-butyl, phenyl, p-hydroxyphenyl, p-methoxyphenyl, or p-nitrophenyl, or 2 wherein Y is a C 1 -C 4 straight or branched-chain alkoxy, or 3 wherein W is N, R5 is hydrogen, methyl, ethyl, n-propyl, isopropyl, or methyl ethanoate 2-yl, and R6 is hydrogen, methyl, ethyl, or n-propyl, or R5 and R6 are part of a pyrrolidine or piperidine ring; X is a C 1 -C 4 straight or branched-chain alkoxy, a primary amino, a N-alkylamino wherein the alkyl is a straight-chain alkyl groups containing from 1 to 4 carbon atoms, methyl ethanoate-2-yl, N-phenylamino, p-nitrophenyl, N,N-dimethylamino, N,N-diethylamino, N,N-di(n-propyl)amino, N-pyrrolidino, or N-piperidino as single compounds, and any mixture of all possible stereoisomers at C(4″). n may be 0, 1, 2, or 3, and methods of making and using thereof. As disclosed herein, the mixed steroidal tetraoxanes of the present invention exhibit antimalarial, antibacterial, and antiproliferative activity. Thus, as disclosed herein, the mixed steroidal tetraoxanes of the present invention may be used to treat, prevent, or inhibit malaria, bacterial infections, and diseases and disorders associated with cell proliferation in a subject.

  本文披露了具有以下结构式1的混合类固醇四氧杂环戊烷： 1 其中n为0、1、2或3；R为H；乙酰基、丙酰基或苯甲酰基；R1为H、甲基、乙基或异丙基；R2为H、甲基或乙基；R3为H、甲基或乙基；R4为H、甲基、乙基、叔丁基、苯基、对羟基苯基、对甲氧基苯基或对硝基苯基，或 2 其中Y为C 1 -C 4 直链或支链烷氧基，或 3 其中W为N，R5为氢、甲基、乙基、正丙基、异丙基或乙酸甲酯-2-基，R6为氢、甲基、乙基或正丙基，或R5和R6是吡咯烷或哌啶环的一部分；X为C 1 -C 4 直链或支链烷氧基、一级氨基、N-烷基氨基，其中烷基是含有1至4个碳原子的直链烷基，乙酸甲酯-2-基、N-苯基氨基、对硝基苯基、N,N-二甲基氨基、N,N-二乙基氨基、N,N-二(正丙基)氨基、N-吡咯啉基或N-哌啶基作为单一化合物，以及在C(4″)处的所有可能立体异构体的任何混合物。n可以为0、1、2或3，以及其制备和使用方法。如本文所披露的，本发明的混合类固醇四氧杂环戊烷表现出抗疟疾、抗菌和抗增殖活性。因此，如本文所披露的，本发明的混合类固醇四氧杂环戊烷可用于治疗、预防或抑制受试者体内的疟疾、细菌感染以及与细胞增殖相关的疾病和疾病。
• Mixed Steroidal 1,2,4,5-Tetraoxanes:  Antimalarial and Antimycobacterial Activity
  作者：Bogdan A. Šolaja、Nataša Terzić、Gabriella Pocsfalvi、Lucia Gerena、Bernard Tinant、Dejan Opsenica、Wilbur K. Milhous

  DOI：10.1021/jm020891g

  日期：2002.8.1

  Mixed 1,2,4,5-tetraoxanes possessing simple spirocycloalkane and spirocholic acid-derived substituents were prepared and shown to have significantly higher in vitro antimalarial activity than bis-substituted tetraoxanes. Out of 41 synthesized tetraoxanes, 12 were in vitro more potent against Plasmodium falciparum chloroquine-resistant W2 clone than artemisinin, and the most potent one was 2.4 times as active as arteether. In addition, 9 compounds exhibit higher activity than chloroquine against P. falciparum chloroquine-susceptible D6 clone. Cytotoxicity was assessed for most active compounds against the Vero cell line, showing a cytotoxicity/antimalarial potency ratio of 1/(1400-9500). For the first time, tetraoxanes were screened against Mycobacterium tuberculosis with MICs as low as 4.73 muM against H37Rv strain. Mixed tetraoxanes were synthesized in a simple procedure from cholic acid methyl esters by direct coupling of steroidal gem-dihydroperoxide to simple ketones and further transformed into corresponding acids and amides.
• Mixed tetraoxanes containing the acetone subunit as antimalarials
  作者：Dejan M. Opsenica、Nataša Terzić、Philip L. Smith、Youngsun Yang、Lalaine Anova、Kirsten S. Smith、Bogdan A. Šolaja

  DOI：10.1016/j.bmc.2008.05.017

  日期：2008.7

  Eleven new tetraoxanes possessing cholic acid-derived carrier and isopropylidene moiety were synthesized and were tested in vitro and in vivo. In vitro screening revealed that nine of them were more potent against CQ-resistant W2 than CQ-susceptible D6 strain and that two of them were equally or more potent than artemisinin and mefloquine against multi- drug resistant TM91C235 strain. Amine 8 cured all mice at the dose of 160 mg/kg/day, while the anilide 9 exhibited MCD <= 20 mg/kg/day. The diol 13 was most potent antiproliferative with GI(50), TGI, LC50 MG_MID 0.98 mu M, 3.80 mu M, 11.22 mu M, respectively. All tested compounds showed no toxic effects. (c) 2008 Elsevier Ltd. All rights reserved.
• US6906098B2
  申请人：——

  公开号：US6906098B2

  公开（公告）日：2005-06-14
• [EN] MIXED STEROIDAL 1,2,4,5-TETRAOXANE COMPOUNDS AND METHODS OF MAKING AND USING THEREOF<br/>[FR] COMPOSES MELANGES DE STEROIDES 1,2,4,5-TETRAOXANE ET PROCEDES DE FABRICATION ASSOCIES
  申请人：US ARMY MED RES MAT COMMAND

  公开号：WO2003068736A2

  公开（公告）日：2003-08-21

  Disclosed herein are mixed steroidal tetraoxanes having the following structural Formula (I), wherein n is 0, 1, 2, or 3; R is H; ethanoyl, propanoyl, or benzoyl; R1 is H, methyl, ethyl, or isopropyl; R2 is H, methyl, or ethyl; R3 is H, methyl, or ethyl; R4 is H, methyl, ethyl, tert-butyl, phenyl, p-hydroxyphenyl, p-methoxyphenyl, or p-nitrophenyl, or Formula (a), wherein Y is C1-C4 straight or branched-chain alkoxy, or Formula (b), wherein W is N, R5 is hydrogen, methyl, ethyl, or n-propyl, isopropyl, or methyl ethanoate 2-yl, and R6 is hydrogen, methyl, ethyl, or n-propyl, or R5 and R6 are part of a pyrrolidine or piperidine ring; X is a C1-C4 straight or branched-chain alkoxy, a primary amino, a N-akylamino wherein the alkyl is a straight-chain alkyl groups containing from 1 to 4 carbon atoms, methyl ethanoate-2-yl, N-phenylamino, p-nitrophenyl, N,N-dimethylamino, N,N-diethylamino, N,N-di(n-propyl)amino, N-pyrrolidino, or N-piperidino as single compounds, and any mixture of all possible stereoisomers at C(4’’). n may be 0, 1, 2, or 3, and methods of making and using thereof. As disclosed herein, the mixed steroidal tetraoxanes of the present invention exhibit antimalarial, antibacterial, and antiproliferative activity. Thus, as disclosed herein, the mixed steroidal tetraoxanes of the present invention may be used to treat, prevent, or inhibit malaria, bacterial infections, and diseases and disorders associated with cell proliferation in a subject.