(3R,12aR)-3,6a,9b-三甲基-3b,12a-环氧-3,4,5,5aa,6,7,8,8aa,9,10-十氢-10a-乙氧基吡喃并[4,3-j]-1,2-苯并二氧杂卓 | 82534-75-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: (3R,12aR)-3,6a,9b-三甲基-3b,12a-环氧-3,4,5,5aa,6,7,8,8aa,9,10-十氢-10a-乙氧基吡喃并[4,3-j]-1,2-苯并二氧杂卓
• 英文名称: Alpha-Arteether
• 英文别名: α-arteether；(1R,4S,5R,8S,9R,10R,12R,13R)-10-ethoxy-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane
• CAS: 82534-75-6
• 化学式: C₁₇H₂₈O₅
• 分子量: 312.406
• InChiKey: NLYNIRQVMRLPIQ-LTLPSTFDSA-N

物化性质

• 沸点：
  372.4±42.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  46.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3R,12aR)-3,6a,9b-三甲基-3b,12a-环氧-3,4,5,5aa,6,7,8,8aa,9,10-十氢-10a-乙氧基吡喃并[4,3-j]-1,2-苯并二氧杂卓 在 Lindlar's catalyst 氢气 作用下， 以 乙醇 为溶剂， 以67%的产率得到α-deoxydihydroqinghaosu ethyl ether
  参考文献：
  名称：

  Arteether, a new antimalarial drug: synthesis and antimalarial properties

  摘要：

  Arteether (6) has been prepared from dihydroquinghaosu (3) by etherification with ethanol in the presence of Lewis acid and separated from its chromatographically slower moving alpha-dihydroqinghaosu ethyl ether (7). The absolute stereochemistry at C-12 has been determined by 1H NMR data (J11,12, NOESY). Ethyl ethers 6 and 7 showed potent in vitro inhibition of Plasmodium falciparum, and both compounds were highly potent antimalarials in mice infected with a drug-sensitive strain of Plasmodium berghei. Crystalline arteether (6) and its oily epimer 7 were 2-3 times more potent schizontocides than quinghaosu (1), but deoxy compounds 8, 9, and 11 were 100-300 times less potent in vitro than their corresponding peroxy precursors. Pharmacological studies have shown arteether(6) to have antimalarial activity in animals comparable to artesunate (2) and artemether (4), both of which are fast-acting blood schizontocides in humans. Arteether (6) has now been chosen for a clinical evaluation in high-risk malaria patients.

  DOI：

  10.1021/jm00398a026
• 作为产物：
  描述：

  青蒿素 在 sodium tetrahydroborate 、 三氟化硼乙醚 作用下， 以 甲醇 为溶剂， 生成 (3R,12aR)-3,6a,9b-三甲基-3b,12a-环氧-3,4,5,5aa,6,7,8,8aa,9,10-十氢-10a-乙氧基吡喃并[4,3-j]-1,2-苯并二氧杂卓
  参考文献：
  名称：

  Madhusudanan; Vishwakarma; Balachandran, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1989, vol. 28, # 9, p. 751 - 754

  摘要：

  DOI：

文献信息

• One-pot green synthesis of β-artemether/arteether
  作者：Atul Kumar、Ajay Kumar Bishnoi

  DOI：10.1039/c4ra05531d

  日期：——

  We have developed an efficient one pot green synthesis of β-artemether/arteether from artemisinin, which involves combination of a sodium borohydride – cellulose sulfuric acid (CellSA) catalyst system. This green methodology is high yielding and the catalyst has good recyclability. The developed methodology is simple, cost-effective and the catalyst used is eco-friendly, reusable, and biodegradable.

  我们已经开发出一种高效的一锅绿色合成β-青蒿素/青蒿醚的方法，该方法涉及将硼氢化钠和纤维素硫酸催化剂（CellSA）系统结合在一起。这种绿色方法产率高，催化剂具有良好的可回收性。所开发的方法简单、成本效益高，所使用的催化剂环保、可重复使用且可生物降解。
• [EN] SINGLE POT CONVERSION OF ARTEMISININ INTO ARTEETHER<br/>[FR] CONVERSION D'ARTEMISINE EN ARTEETHER EN FOUR MONOCELLULAIRE
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2004050662A1

  公开（公告）日：2004-06-17

  The present invention provides a method for the preparation of arteether from artemisinin in one pot in just about 4 hours comprising reduction of artemisinin into dihydroartemisinin by less quantity of sodium borohydride in ethanol at room temperature in the presence of a novel polyhydroxy catalyst, acylation of dihydroartemisinin in the presence of an acid catalyst, extraction of arteether from an aqueous reaction mixture using 1% ethyl acetate in n-hexane followed by workup and purification of the impure arteether to yield 80-86% (w/w) pure alpha, beta arteether.

  该发明提供了一种从青蒿素制备缬草酯的方法，该方法在一个锅中仅需约4小时，包括在室温下在乙醇中使用少量硼氢化钠将青蒿素还原为二氢青蒿素，在新型多羟基催化剂的存在下，通过酸催化剂对二氢青蒿素进行酰化，使用1%乙酸乙酯在正己烷中从水相反应混合物中提取缬草酯，然后进行处理和纯化以得到80-86%（质量百分比）纯度的α，β缬草酯。
• Structure-activity relationship study of dihydroartemisinin C-10 hemiacetal derivatives as Toll-like receptor 4 antagonists
  作者：Shuo Wang、Hongshuang Wang、Cong Lin、Tianshu Zhang、Jingwei Gao、Siru Wu、Yibo Wang、Hongyuan Li、Weihong Min、Chunlei Liu、Xiaohui Wang

  DOI：10.1016/j.bioorg.2021.105107

  日期：2021.9

  recently been discovered as a Toll-like Receptor 4 (TLR4) antagonist. However, the TLR4 antagonistic activity of DHA is modest and it exhibits cellular toxicity. In this work, the structure-activity relationship (SAR) of DHA as TLR4 antagonist was explored. Since destroying the sesquiterpene endoperoxide scaffold substantially compromised the TLR4 antagonistic activity and molecular dynamics analysis

  双氢青蒿素(DHA)，一种从传统中草药青蒿中分离出来的天然产物作为一种抗疟疾感染的临床一线药物，最近被发现是一种 Toll 样受体 4 (TLR4) 拮抗剂。然而，DHA 的 TLR4 拮抗活性是适度的，并且表现出细胞毒性。在这项工作中，探索了 DHA 作为 TLR4 拮抗剂的构效关系 (SAR)。由于破坏倍半萜内过氧化物支架显着损害了 TLR4 拮抗活性，分子动力学分析表明 C-10 羟基与髓细胞分化因子 2 (MD2) 的 E72 形成氢键以防止其深入 MD2，因此 DHA 的 SAR 为专注于 C-10 半缩醛位置。随着在 C10 位置延长直链烷烃链的长度，DHA 类似物的 TLR4 拮抗活性先增加后降低，最好的 TLR4 拮抗作用发生在 3-4 个碳的碳链长度处。相比之下，DHA 类似物的细胞毒性随着线性烷烃链长度的增加而增加。以取代卤素为末端官能团的DHA衍生物的TLR4拮抗活性
• New Method for the Synthesis of Ether Derivatives of Artemisinin
  作者：Pranjal P. Bora、Nabajyoti Baruah、Ghanashyam Bez、Nabin C. Barua

  DOI：10.1080/00397911.2010.538887

  日期：2012.4.15

  Dihydroartemisinin can be converted to its ether derivatives in good yields by reaction with different alcohols in the presence of a catalytic amount of dodecatungstophosphoric acid hydrate. Easy handling, trouble-free workup by filtration, excellent yields, and very short reaction times are some of the highlights of this protocol.
• Pathak, Ashish K.; Jain, Dharam C.; Sharma, Ram P., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1994, vol. 33, # 6, p. 613
  作者：Pathak, Ashish K.、Jain, Dharam C.、Sharma, Ram P.

  DOI：——

  日期：——