- Method and apparatus for the synthesis of dihydroartemisinin and artemisinin derivatives
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The present invention is directed to a method for continuous production of dihydroartemisinin and also artemisinin derivatives derived from dihydroartemisinin by using artemisinin or dihydroartemisinic acid (DHAA) as starting material as well as to a continuous flow reactor for producing dihydroartemisinin as well as the artemisinin derivatives. It was found that the reduction of artemisinin to dihydroartemisinin in a continuous process requires a special kind of reactor and a special combination of reagents comprising a hydride reducing agent, at least one activator such as an inorganic activator, at least one solid base, at least one aprotic solvent and at least one C1-C5 alcohol.
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- One-pot green synthesis of β-artemether/arteether
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An efficient one pot green synthesis of β-artemether/arteether from artemisinin has been developed using a sodium borohydride-cellulose sulfuric acid (CellSA) catalyst system. The green methodology is high yielding and the catalyst has good recyclability.
- Kumar, Atul,Bishnoi, Ajay Kumar
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p. 31973 - 31976
(2014/08/18)
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- New method for the synthesis of ether derivatives of artemisinin
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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. Copyright Taylor & Francis Group, LLC.
- Bora, Pranjal P.,Baruah, Nabajyoti,Bez, Ghanashyam,Barua, Nabin C.
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p. 1218 - 1225
(2012/04/04)
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- A NOVEL PROCESS FOR THE PREPARATION OF ETHERS OF DIHYDROARTEMISININ
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A process for the preparation of ethers of dihydroartemisinin containing more than 99 % of ? isomer from dihydroartemisinin which comprises: reacting dihydroartemisinin with an alcohol and hydrolysable organic halides as a pro-acid catalyst in the presence of a co-solvent at 0 - 45 °C; diluting the reaction mixture with an aqueous solution of mild bases such as sodium bicarbonate, sodium acetate or triethanolamine; cooling the reaction mass to 0 °C-5 °C and stirring to obtain the solid product; filtering the solid to obtain the ethers of dihydroartemisinin; recrystallizing the product from suitable solvent mixture such as alcohol and water to obtain ethers of dihydroartemisinin containing more than 99 % of ? isomer.
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Page/Page column 10
(2009/10/22)
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- PREPARATIVE PROCESS FOR ETHER DERIVATIVE OF ARTEMISININ
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The present invention relates to a process for synthesis of ether derivative of artemisinin by reducing artemisinin to dihydroartemisinin using a mixture of sodium borohydride and a dihydroxy compound, followed by etherification in presence of an acid catalyst and an alcohol.
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Page/Page column 11; 12; 14; 15
(2008/12/07)
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- SINGLE POT CONVERSION OF ARTEMISININ INTO ARTEETHER
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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.
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- SINGLE POT CONVERSION OF ARTEMISININ INTO ARTEETHER
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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.
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- Process for the preparation of arteethers from dihydroartemisinin
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The invention relates to an improved process for the preparation of arteether. The process comprises dissolving dihydroartemisinin in dry ethanol, adding a solid acid catalyst with trialkylorthoformate in the reaction mixture, stirring the reaction mixture at room temperature, adding H2O to the reaction mixture, extracting the reaction product with a non-polar organic solvent, and drying the solvent over anhydrous sodium sulphate and evaporating the solvent to obtain pure arteether.
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Page column 4
(2008/06/13)
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- Synthesis and cytotoxicity of novel artemisinin analogs
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A series of artemisinin-related analogs has been synthesized and assayed in vitro cytotoxicity. 12-Ethyl-, 12-n-butyl-, homo- and 12-(N,N-diethylaminomethylbenzoyl)- deoxoartemisinins show a good cytotoxicity against P388 and KB cell lines, respectively.
- Jung, Mankil
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p. 1091 - 1094
(2007/10/03)
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- An improved procedure for the synthesis of ethers of dihydroartemisinin
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A simple and efficient method for the preparation of ethers (3a-f) of dihydroartemisinin (2) has been developed using chlorotrimethylsilane as a catalyst.
- Bhakuni, Rajendra S.,Jain, Dharam C.,Sharma, Ram P.
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p. 529 - 530
(2007/10/02)
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- Antimalarial activity of new ethers and thioethers of dihydroartemisinin
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Various ethers and thioethers of dihydroartemisinin were prepared by treating dihydroartemisinin with hydroxy alkyl, substituted phenol, hydroxy aralkyl, hydroxy alkynyl and hydroxy heteroalkyl or thiols in the presence of BF3Et2O.The thioethers 64 and 65 were further oxidised to the respective sulfoxides.These derivatives were tested in the Plasmodium berghei K-173-infected mice and some active compounds were tested in chloroquine-resistant P yoelii nigeriensis (NS)-infected mice.Initially the compounds were administered subcutaneously and subsequently by the oral route.The antimalarial activity of the compounds 22, 23, 36, 66 and 79 were found to be comparable to that of arteether when tested in the K-173-infected mice.These compounds also showed activity in the P y nigieriensis (NS)-infected mice.Antimalarial activity / artemisinin / dihydroartemisinin / ether / thioether
- Venugopalan, B.,Karnik, P. J.,Bapat, C. P.,Chatterjee, D. K.,Iyer, N.,Lepcha, D.
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p. 697 - 706
(2007/10/03)
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- Diastereofacial Additions to a &β-Substituted Glycal, Anhydrodihydroartemisinin
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Triphenylphosphine hydrobromide catalyzed electrophilic addition of ethanol to the carbon-carbon double bond of anhydrodihydroartemisinin occurs predominately from the β-face of the molecule.
- Pu, Yu Ming,Ziffer, Herman
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p. 649 - 656
(2007/10/02)
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- Arteether, a new antimalarial drug: Synthesis and antimalarial properties
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Arteether (6) has been prepared from dihydroqinghaosu (3) by etherification with ethanol in the presence of Lewis acid and separated from its chromatographically slower moving α-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 qinghaosu (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.
- Brossi,Venugopalan,Gerpe,Yeh,Flippen-Anderson,Buchs,Luo,Milhous,Peters
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p. 645 - 650
(2007/10/02)
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