- Concise Synthesis of Anti-HIV-1 Active (+)-Inophyllum B and (+)-Calanolide A by Application of (-)-Quinine-Catalyzed Intramolecular Oxo-Michael Addition
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(-)-Quinine-catalyzed intramolecular oxo-Michael addition (IMA) of 7-hydroxy-5-methoxy-8-tigloylcoumarins was developed for the enantioselective construction of 2,3-dimethyl-4-chromanone systems in the context of the asymmetric synthesis of anti-HIV-1 act
- Sekino, Etsuko,Kumamoto, Takuya,Tanaka, Tomohiro,Ikeda, Tomoko,Ishikawa, Tsutomu
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p. 2760 - 2767
(2007/10/03)
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- PROCESSES FOR PREPARING CALANOLIDE A AND INTERMEDIATES THEREOF
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The present invention provides a production method of Calanolide A according to the following method wherein each symbol is as defined in the specification, as a more convenient and industrially practical method for the synthesis of Calanolide A from an easily available starting material.
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Page/Page column 22
(2008/06/13)
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- Methods for preparing antiviral calanolide compounds
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The present invention relates to methods for preparing 2,2-dimethyl-5-acyloxy-10-propyl-2H,8H-benzo[ 1,2-b:3,4-b ′]dipyran-8-one (5) and 2,2-dimethyl-5-hydroxy- 10-propyl-2H,8H-benzo[1,2-b:3,4-b ′]dipyran-8-one (6) and their use as intermediates for the synthesis of antiviral calanolide compounds. For example, Fries rearrangement on compound 5 or Friedel-Crafts reaction on 6, yields intermediate 2,2-dimethyl-5-hydroxy-6-propionyl-10-propyl-2H,8H-benzo[1,2-b:3,4-b′]dipyran-8-one (4), which, in turn, can be converted to (+)-calanolide A and (?)-calanolide B. The coupling of compound 6 with the appropriate chiral molecule under Mitsunobu or nucleophilic displacement leads to the asymmetric synthesis of antiviral calanolide compounds.
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- Methods for preparing antiviral calanolide compounds
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The present invention relates to methods for preparing 2,2-dimethyl-5-acyloxy-10-propyl-2H,8H-benzo[1,2-b:3,4-b′]dipyran-8-one (5) and 2,2-dimethyl-5-hydroxy-10-propyl-2H,8H-benzo[1,2-b:3,4-b′]dipyran-8-one (6) and their use as intermediates for the synthesis of antiviral calanolide compounds. For example, Fries rearrangement on compound 5 or Friedel-Crafts reaction on 6, yields intermediate 2,2-dimethyl-5-hydroxy-6-propionyl-10-propyl-2H,8H-benzo[1,2-b:3,4-b′]dipyran-8-one (4), which, in turn, can be converted to (+)-calanolide A and (?)-calanolide B. The coupling of compound 6 with the appropriate chiral molecule under Mitsunobu or nucleophilic displacement leads to the asymmetric synthesis of antiviral calanolide compounds.
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- Method for treating and preventing mycobacterium infections
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Calanolides and analogues thereof that demonstrate potent mycobacterium activity are provided. Also provided is a method of using calanolides and analogues thereof for treating or preventing mycobacterium infections. The calanolides and analogues thereof provided are obtained via syntheses employing chromene 4 and chromanone 7 as key intermediates.
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- Calanolide analogues and methods of their use
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Calanolide analogues that demonstrate potent antiviral activity against many viruses are provided. Also provided is a method of using calanolide analogues for treating or preventing viral infections. The calanolide analogues provided are obtained via syntheses employing chromene 4 and chromanone 7 as key intermediates.
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- Enantioselective total synthesis of anti HIV-1 active (+)-calanolide A through a quinine-catalyzed asymmetric intramolecular oxo-Michael addition
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Enantioselective total synthesis of anti HIV-1 active (+)-calanolide A was achieved by a quinine-catalyzed asymmetric intramolecular oxo-Michael addition as a key step. (C) 2000 Elsevier Science Ltd.
- Tanaka, Tomohiro,Kumamoto, Takuya,Ishikawa, Tsutomu
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p. 10229 - 10232
(2007/10/03)
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- Method for the preparation of (+)-calanolide a and analogues thereof
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A method of preparing (+)-calanolide A, 1, a potent HIV reverse transcriptase inhibitor, from chromene 4 is provided. According to the disclosed method, chromene 4 intermediate was subjected to a chlorotitanium-mediated aldol reaction with acetaldehyde to selectively produce (±)-8a. Separation and enzyme-mediated resolution of (±)-8a produced (+)-8a. Cyclization of (+)-8a under neutral Mitsunobu conditions followed by Luche reduction of (+)-7 produced (+)-calanolide A in high yield and enantiomeric purity. The method of the invention has been extended to produce potent antiviral calanolide A analogues.
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- Method for the preparation of (+)-calanolide A and analogues thereof
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A method of preparing (+)-calanolide A, 1, a potent HIV reverse transcriptase inhibitor, from chromene 4 is provided. According to the disclosed method, chromene 4 intermediate was subjected to a chlorotitanium-mediated aldol reaction with acetaldehyde to selectively produce (±)-8a. Separation and enzyme-mediated resolution of (±)-8a produced (+)-8a. Cyclization of (+)-8a under neutral Mitsunobu conditions followed by Luche reduction of (+)-7 produced (+)-calanolide A in high yield and enantiomeric purity. The method of the invention has been extended to produce potent antiviral calanolide A analogues.
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- Synthesis of (+)-calanolide A, an anti-HIV agent, via enzyme-catalyzed resolution of the aldol products
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The synthesis of (+)-calanolide A (1), an anti-HIV-1 agent, is described. A TiCl4-mediated aldol reaction of compound 2 stereoselectively produced the desired syn diastereomer (±)-5, which was resolved by a lipase-catalyzed acylation reaction. Under Mitsunobu conditions (Ph3P/DEAD), the syn aldol product (+)-5 led to the formation of trans-2,3-dimethyl chroman-4-one [(+)-3] with 94% ee, while the anti aldol product (+)-6 yielded both trans and cis derivatives (+)-3 and (+)-4 with 60% and 68% ee, respectively. Luche reduction on (+)-3 led to (+)-1 and (+)-calanolide B in a ratio of 9:1. Copyright (C) Elsevier Science Ltd.
- Khilevich, Albert,Mar, Aye,Flavin, Michael T.,Rizzo, John D.,Lin, Lin,Dzekhtser, Sergey,Brankovic, Darko,Zhang, Heping,Chen, Wei,Liao, Shuyuan,Zembower, David E.,Xu, Ze-Qi
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p. 3315 - 3326
(2007/10/03)
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- Structure-activity modifications of the HIV-1 inhibitors (+)-calanolide A and (-)-calanolide B
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The Δ7,8 olefinic linkages within (+)-calanolide A (1) and (-)- calanolide B (2) were catalytically reduced to determine impact on the anti- HIV activity of the parent compounds. In addition, a series of structure modifications of the C-12 hydroxyl group in (-)-calanolide B was made to investigate the importance of that substituent to the HIV-1 inhibitory activity of these coumarins. A total of 14 analogs were isolated or prepared and compared to (+)-calanolide A and (-)-calanolide B in the NCI primary anti-HIV assay. While none of the compounds showed activity superior to the two unmodified leads, some structure-activity requirements were apparent from the relative anti-HIV potencies of the various analogs.
- Galinis, Deborah L.,Fuller, Richard W.,McKee, Tawnya C.,Cardellina II, John H.,Gulakowski, Robert J.,McMahon, James B.,Boyd, Michael R.
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p. 4507 - 4510
(2007/10/03)
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