86386-74-5Relevant articles and documents
Organomagnesium Based Flash Chemistry: Continuous Flow Generation and Utilization of Halomethylmagnesium Intermediates
Von Keutz, Timo,Cantillo, David,Kappe, C. Oliver
supporting information, p. 7537 - 7541 (2020/10/12)
The generation of highly unstable chloromethylmagnesium chloride in a continuous flow reactor and its reaction with aldehydes and ketones is reported. With this strategy, chlorohydrins and epoxides were synthesized within a total residence time of only 2.6 s. The outcome of the reaction can be tuned by simply using either a basic or an acidic quench. Very good to excellent isolated yields, up to 97%, have been obtained for most cases (30 examples).
The Application of a Continuous Grignard Reaction in the Preparation of Fluconazole
Korwar, Sudha,Amir, Somi,Tosso, Perrer N.,Desai, Bimbisar K.,Kong, Caleb J.,Fadnis, Swara,Telang, Nakul S.,Ahmad, Saeed,Roper, Thomas D.,Gupton, B. Frank
supporting information, p. 6495 - 6498 (2017/11/16)
The application of continuous methods in the synthesis of active pharmaceutical ingredients continues to receive significant attention in the academic as well as the industrial research communities. One of the major advantages of continuous methods is the ability to safely access kinetic synthons as well as highly reactive reagents that are typically unavailable through traditional batch methods. In this work, we report the high-yielding, clean formation of an aryl-turbo Grignard and its selective addition to a highly-enolizable 1,3-dichloroacetone, for the continuous synthesis of a key intermediate for fluconazole, a widely-prescribed anti-fungal agent. In addition, process optimization of the final API was also carried out to arrive at a semi-continuous method to this essential medicine.
Asymmetric synthesis, antifungal activity and molecular modeling of iodiconazole isomers
Zhang, Yongqiang,Wang, Shengzheng,Miao, Zhenyuan,Yao, Jianzhong,Zhang, Wannian,Sheng, Chunquan
, p. 1139 - 1143 (2013/10/21)
Iodiconazole is a novel antifungal agent that was developed in its racemic form. In order to investigate the effects of the chiral center on the antifungal activity, R- and S-isomers of iodiconazole were prepared on the basis of the asymmetric Sharpless epoxidation. (S)-Iodiconazole was proved to have better antifungal activity than the (R)-isomer. The binding modes of the two isomers with lanosterol 14α-demethylase were clarified by molecular docking. Two isomers of iodiconazole, a novel antifungal agent, were prepared by asymmetric synthesis. Their antifungal activity and binding modes were investigated. Copyright
An improved method for the addition reactions of 1,3-dichloroacetone with combined organolithium-cerium trichloride reagents
Chen, Same-Ting,Fang, Jim-Min
, p. 927 - 930 (2007/10/03)
Alkyl-, phenyl- and alkynyllithium reagents in combination with anhydrous cerium(III) chloride underwent addition reactions with 1,3-dichloroacetone in a very efficient manner. The addition products are versatile precursors for 2-substituted epichlorohydrins and glycidols. Fluconazole, a potent antifungal agent, was thus synthesized in 67% yield by addition of 1,3-dichloroacetone to 2,4-difluorophenyllithium in the presence of cerium(III) chloride, followed by substitution of the chlorine atoms with 1,2,4-triazole.
A practical chemoenzymatic synthesis of a key intermediate of antifungal agents
Yasohara, Yoshihiko,Miyamoto, Kenji,Kizaki, Noriyuku,Hasegawa, Junzo,Ohashi, Takehisa
, p. 3331 - 3333 (2007/10/03)
A novel synthesis of an azole antifungal building block, the optically active diol, is described. The key step involves an enantioselective hydrolysis of a prochiral diester by a lipase.
