- AN IMPROVED PROCESS FOR THE PREPARATION OF TRIAZOLE DERIVATIVES
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The present invention relates to an improved process for the preparation of triazole derivatives such as ravuconazole and isavuconazole.
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- An enantioselective synthesis of the key intermediate for triazole antifungal agents; Application to the catalytic asymmetric synthesis of efinaconazole (jublia)
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A new synthetic route, the shortest reported to date, to access a key intermediate for the synthesis of various triazole antifungal agents was developed. The elusive tetrasubstituted stereogenic center that is essential in advanced triazole antifungal agents was constructed via the catalytic asymmetric cyanosilylation of a ketone. The subsequent transformations were performed in two one-pot operations, enhancing the overall synthetic efficiency toward the intermediate. This streamlined synthetic approach was successfully applied to efficient enantioselective syntheses of efinaconazole (Jublia) and ravuconazole.
- Tamura, Keiji,Kumagai, Naoya,Shibasaki, Masakatsu
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p. 3272 - 3278
(2014/05/06)
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- Process for the manufacture of enantiomerically pure antifungal azoles as ravuconazole and isavuconazole
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A new technical process for preparation of enantiomerically pure antifungal compounds of formula I by resolution of the racemates has been disclosed.
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Page/Page column 7-8
(2011/04/25)
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- The process development of ravuconazole: An efficient multikilogram scale preparation of an antifungal agent
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The development of a safe, robust process for the preparation of ravuconazole (1), an antifungal agent, is described. The discovery and development of procedures enabling the efficient synthesis of multikilogram quantities of 1 and the process demonstration through plant scale preparations are presented. A controlled means to prepare a Grignard reagent and utilization of Fourier Transform Infrared spectroscopy (FTIR) monitoring to safely conduct the reaction is featured.
- Pesti, Jaan,Chen, Chien-Kuang,Spangler, Lori,DelMonte, Albert J.,Benoit, Serge,Berglund, Derek,Xbien, Derek,Brodfuehrer, Paul,Chan, Yeung,Corbett, Elisabeth,Costello, Carrie,DeMena, Paul,Discordia, Robert P.,Doubleday, Wendel,Gao, Zhinong,Gingras, Stephane,Grosso, John,Haas, Oscar,Kacsur, David,Lai, Chiajen,Leung, Simon,Miller, Melanie,Muslehiddinoglu, Jale,Nguyen, Nina,Qiu, Jun,Olzog, Martina,Reiff, Emily,Thoraval, Dominique,Totleben, Michael,Vanyo, Dale,Vemishetti, Purushotham,Wasylak, John,Wei, Chenkou
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experimental part
p. 716 - 728
(2010/04/22)
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- Improved chiral synthesis of ravuconazole
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A short, elegant, and high yielding synthesis of ravoconazole is presented. The key step of this synthesis is an enantioselective palladium-catalyzed chiral zinc-allene addition reaction. The starting materials are 2-chloro-1-(2,4-difluorophenyl)-ethanone and (R)-4-phenylbutyn-2-ol obtained from enzymatic resolution of its racemate. Copyright Taylor & Francis Group, LLC.
- Xu, Lin,Muller, Marc R.,Yu, Xiong,Zhu, Bao-Quan
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experimental part
p. 1611 - 1625
(2009/10/17)
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- Synthesis and antifungal activity of novel thiazole-containing triazole antifungals. II. Optically active ER-30346 and its derivatives
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A series of novel thiazole-containing triazole antifungals was synthesized and evaluated for antifungal activity against a variety of clinically isolated pathogenic fungi in vitro and against systemic candidosis in vivo. These compounds showed potent antifungal activities in vitro and in vivo. In particular, (2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4- difluorophenyl)-1-(1H-1,2,4-triazol-l-yl)-2-butanol (12g; ER-30346) showed potent and well-balanced in vitro activities and potent in vivo efficacy, and had a good safety profile.
- Tsuruoka, Akihiko,Kaku, Yumiko,Kakinuma, Hiroyuki,Tsukada, Itaru,Yanagisawa, Manabu,Nara, Kazumasa,Naito, Toshihiko
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p. 623 - 630
(2007/10/03)
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