methyl 3-keto-7,12-diacetylcholate | 4947-65-3

• 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 3-keto-7,12-diacetylcholate
• 英文别名: methyl 3-oxo,7α,12α-diacetoxy-5β-cholan-24-oate；methyl 3-oxo-7α,12α-diacetoxy-5β-cholan-24-oate；methyl 7α,12α-diacetoxy-3-oxo-5β-cholan-24-oate；methyl 7,12-diacetoxy-3-oxo-5β-cholan-24-oic acid；methyl 7,12-diacetoxy-5β-cholan-24-oate；7α.12α-diacetoxy-3-oxo-5β-cholanoic acid-(24)-methyl ester；5beta-Cholan-24-oic acid, 7alpha,12alpha-dihydroxy-3-oxo-, methyl ester, diacetate；methyl (4R)-4-[(5R,7R,8R,9S,10S,12S,13R,14S,17R)-7,12-diacetyloxy-10,13-dimethyl-3-oxo-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-17-yl]pentanoate
• CAS: 4947-65-3
• 化学式: C₂₉H₄₄O₇
• 分子量: 504.664
• InChiKey: KTOYRTMQPLELSO-GDQXCEHNSA-N

物化性质

• 沸点：
  559.2±50.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  96
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 3-keto-7,12-diacetylcholate 在 盐酸 、 sodium hydroxide 、 硫酸 、 双氧水 作用下， 以 二氯甲烷 、 水 、 异丙醇 、 乙腈 为溶剂， 反应 2.75h， 生成 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：

  胆酸 在 吡啶 、 4-二甲氨基吡啶 、 乙酰氯 、 pyridinium chlorochromate 作用下， 以 甲醇 为溶剂， 生成 methyl 3-keto-7,12-diacetylcholate
  参考文献：
  名称：

  由胆酸合成甾族环二聚体；具有识别和催化潜力的分子框架

  摘要：

  大环化合物（2a – f）由胆酸（1a）合成，总收率高达33％；它们所基于的“胆碱”框架具有很大的潜在可变性，应该证明在仿生化学中很有用。

  DOI：

  10.1039/c39890001050

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。
• Synthesis and X-ray crystal structure of a new ‘cholaphane’ with externally directed functionality
  作者：Anthony P. Davis、Michael G. Orchard、Alexandra M. Z. Slawin、David J. Williams

  DOI：10.1039/c39910000612

  日期：——

  The ‘cholaphane’1 was synthesized in 26% overall yield from cholic acid and its structure determined by X-ray crystallography; the molecule adopts an open conformation and is able to surround two molecules of tetrahydrofuran.

  “胆酸酯（cholaphane）”是以26%的总产率从胆酸合成的，其结构通过X射线晶体学确定；该分子采用开放构象，并能够包围两个四氢呋喃分子。
• New 9-aminoacridine derivatives as inhibitors of Botulinum neurotoxins and P. falciparum malaria
  作者：Miklos Tot、Dejan Opsenica、Milena Mitric、James Burnett、Laura Gomba、Sina Bavari、Bogdan Solaja

  DOI：10.2298/jsc130924112t

  日期：——

  Steroidal and adamantane aminoacridine derivatives were prepared and tested as both botulinum neurotoxin (BoNT) inhibitors and antimalarials. Steroid-bound acridines provided good potency against both the BoNT/A and BoNT/B light chains (LCs). The observed inhibition of the BoNT/B LC by ca. 50% is the highest attained inhibitory activity against this serotype by acridine-based compounds to date. With respect to antimalarial activity, adamantane acridines were the most potent derivatives (IC50 = 6-9 nM, SI > 326), indicating that an adamantyl group is a better carries than a steroidal motif for this indication.

  制备了类固醇和金刚烷氨基吖啶衍生物，并将其作为肉毒杆菌神经毒素（BoNT）抑制剂和抗疟药物进行了测试。 作为肉毒杆菌神经毒素（BoNT）抑制剂和抗疟药物进行了测试。 类固醇结合的吖啶对 BoNT/A 和 BoNT/B轻链（LCs）都有很好的抑制作用。所观察到的对 BoNT/B LC 的抑制率约为 50%，是所达到的最高抑制率。 50%，这是迄今为止吖啶类化合物对该血清型达到的最高抑制活性。 吖啶类化合物对该血清型的最高抑制活性。在抗疟活性方面 金刚烷吖啶是最有效的衍生物（IC50 = 6-9 nM，SI >； 326），这表明金刚烷基比甾族 基团。
• Synthesis of heterosteroids. First synthesis of oxa steroid from cholic acid
  作者：Malika Ibrahim-Ouali、Nicaise Botsi-Nkomendi、Luc Rocheblave

  DOI：10.1016/j.tetlet.2009.10.141

  日期：2010.1

  We wish to report here a new and efficient partial synthesis of 3-oxa-5β-steroid, the first oxa steroid synthesized from cholic acid.

  我们希望在此报告3-oxa-5β-类固醇的一种新的有效部分合成方法，这是第一种由胆酸合成的oxa类固醇。
• First synthesis of thia steroids from cholic acid
  作者：Malika Ibrahim-Ouali、Luc Rocheblave

  DOI：10.1016/j.steroids.2010.04.006

  日期：2010.10

  Heterosteroids remain interesting due to their potential biological activities. This prompted us to synthesize novel thia steroids possessing the heteroatom in the A-ring. We set out to describe a new and versatile method for preparing 3-thia steroids from cholic acid via a selective oxidation of one hydroxyl group, a Baeyer-Villiger oxidation and a photolysis as the key steps. The characteristic (1)H

  由于其潜在的生物活性，异类固醇仍然令人感兴趣。这促使我们合成在 A 环中具有杂原子的新型硫杂类固醇。我们着手描述一种新的通用方法，通过一个羟基的选择性氧化、Baeyer-Villiger 氧化和光解作为关键步骤，从胆酸制备 3-硫杂类固醇。报告了合成化合物的特征 (1) H 和 (13) C NMR 光谱特征。