Development of the Efficient Synthetic Route for Itraconazole Antifungal Agent

이트라코나졸 항진균제의 효과적인 합성법 개발

  • Baek, Du-Jong (Department of Chemistry, College of Natural Sciences, Sangmyung University)
  • 백두종 (상명대학교 자연과학대학 화학과)
  • Received : 2006.08.24
  • Accepted : 2006.09.18
  • Published : 2006.12.10


In this study, the efficient large-scale synthetic route for itraconazole, triazole antifungal agent, was developed. The original synthetic route for medicinal chemistry reported by Janssen Pharmaceutica was linear (14 linear steps) starting from 2,4-dichloroacetophenone with the total yield of 1.4%, and potential hazardous materials such as methanesulfonyl chloride ($CH_{3}SO_{2}Cl$), hydrogen gas, and sodium hydride (NaH) were used. Furthermore, the expensive 1-acetyl-4-(4-hydroxyphenyl)piperazine and palladium were used in this medicinal chemistry route, thus the manufacturing cost would be practically high. In order to improve the commercial route, we developed the process of 12 step convergent synthesis combining two intermediates which are roughly halves of itraconazole with the total yield of 12.0%, and hazardous materials and expensive reagents were excluded in this process, thus the manufacturing cost could be cut down to a great extent.


Itraconazole;Antifungal agent;Synthesis;Process development


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