methyl 7α,12α-diacetoxy-5β-cholan-24-oate-3-spiro-6'-(1',2',4',5'-tetraoxacyclohexane)-3'-spirocyclohexane | 452302-87-3

• 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 7α,12α-diacetoxy-5β-cholan-24-oate-3-spiro-6'-(1',2',4',5'-tetraoxacyclohexane)-3'-spirocyclohexane
• 英文别名: methyl 7α,12α-diacetoxy-3,3-[cyclohexylidenebis(dioxy)]-5β-cholan-24-oate
• CAS: 452302-87-3
• 化学式: C₃₅H₅₄O₁₀
• 分子量: 634.808
• InChiKey: WESCDBGGMVOYJU-AILUVKHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  45
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  116
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  methyl 7α,12α-diacetoxy-5β-cholan-24-oate-3-spiro-6'-(1',2',4',5'-tetraoxacyclohexane)-3'-spirocyclohexane 在 sodium hydroxide 作用下， 以 水 、 异丙醇 为溶剂， 反应 0.5h， 以89%的产率得到7α,12α-diacetoxy-5β-cholan-24-oic acid-3-spiro-6'-(1',2',4',5'-tetraoxacyclohexane)-3'-spirocyclohexane
  参考文献：
  名称：

  Mixed Steroidal 1,2,4,5-Tetraoxanes:  Antimalarial and Antimycobacterial Activity

  摘要：

  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.

  DOI：

  10.1021/jm020891g
• 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， 反应 0.75h， 生成 methyl 7α,12α-diacetoxy-5β-cholan-24-oate-3-spiro-6'-(1',2',4',5'-tetraoxacyclohexane)-3'-spirocyclohexane
  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

• Chemical Stability of the Peroxide Bond Enables Diversified Synthesis of Potent Tetraoxane Antimalarials
  作者：Igor Opsenica、Dejan Opsenica、Kirsten S. Smith、Wilbur K. Milhous、Bogdan A. Šolaja

  DOI：10.1021/jm701417a

  日期：2008.4.1

  The development of widespread drug resistance to chloroquine (CQ(a)) has resulted in severe health issues for countries in malaria endemic regions. The antimalarial properties of artemisinin 2 and of other peroxides, such as 1,2,4,5-tetraoxacy-cloalkanes (tetraoxanes), have recently begun to be exploited in the development of new approaches to fighting CQ-resistant strains of malaria. New tetraoxanes employing a steroidal backbone have now been prepared that are highly active, are inexpensive, and demonstrate low toXieity.(5,6) A part of our research in this field is focused on the development of a new type of tetraoxane with nonidentical substituents(6) that utilize a steroid and small cyclohexylidene carriers possessing secondary amide bonds. Also, during our work in this field we discovered that tetraoxanes are unusually stable, even. at pH 1.6,(6c) a characteristic that subsequently allowed the synthesis of many interesting derivatives. This communication encompasses the synthesis of various amino-functionalized antimalarials based on the appreciable stability of the tetraoxane moiety to reaction conditions such as reductive amination and LiAlH4 reduction. Their respective antimalarial activities and the pronounced antiproliferative activity of certain products are reported along with in vitro metabolism studies.
• 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.
• Elicitation effects of synthetic 1,2,4,5-tetraoxane and 2,5-diphenyltiophene in shoot cultures of two Nepeta species
  作者：Slavica Dmitrovic、Marijana Skoric、Jelena Boljevic、Neda Anicic、Dragana Bozic、Danijela Misic、Vuk Filipovic、Dejan Opsenica

  DOI：10.2298/jsc160226054d

  日期：——

  The present study was aimed to investigate the elicitation possibility of the main secondary metabolites production in Nepeta cataria L. and N. pannonica L. plants, by exposing them to synthetic compounds from the group of tetraoxanes and tiophenes. The effect of DO63 (1,2,4,5-tetraoxane) and DOVF15 (2,5-diphenyl-tiophene) on the production of cis,trans-nepetalactone (NL) and rosmarinic acid (RA) in two Nepeta species, was investigated in shoots grown on culture medium with addition of synthetic compounds in concentrations ranging from 0.1 to 2 mg L-1. The content of targeted metabolites in tested in vitro shoots depended on the type and the concentration of applied synthetic compounds. Application of DO63, primarily in concentration of 0.1 mg L-1 to 1 mg L-1, affected only NL production in both Nepeta species resulting in increased NL content in treated shoots, while production of RA was not influenced. Addition of DOVF15 caused decrease of RA content in N. pannonica shoots and increase in N. cataria shoots, whereas NL production was not affected. The presented results highlight the possibility of DO63 and DOVF15 application for the elicitation of the main secondary metabolites production in species from the genus Nepeta.

  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。