RESUMEN
The incidence of fungal infections is considered a serious public health problem worldwide. The limited number of antimycotic drugs available to treat human and animal mycosis, the undesirable side effects and toxicities of the currently available drugs, and the emergence of fungal resistance emphasizes the urgent need for more effective antimycotic medicines. In this paper, we describe a rapid, simple, and efficient synthetic route for preparation of the antifungal agent butenafine on a multigram scale. This novel synthetic route also facilitated the preparation of 17 butenafine analogues using Schiff bases as precursors in three steps or less. All the synthesized compounds were evaluated against the yeast, Cryptococcus neoformans/C. gattii species complexes and the filamentous fungi Trichophyton rubrum and Microsporum gypseum. Amine 4bd, a demethylated analogue of butenafine, and its corresponding hydrochloride salt showed low toxicity in vitro and in vivo while maintaining inhibitory activity against filamentous fungi.
RESUMEN
Nature is an irrefutable source of inspiration for the modern man in many aspects. The observation and understanding of nature have allowed the development of new materials, new sources of energies, new drugs etc. Specifically, natural products provide a great contribution to the development of new agents for the treatment of infections and antitumor agents. However, obtaining natural products directly from animals, fungi, bacteria, plants etc has been considered not enough to attend the high demand by pharmaceutical industries. In this regard, various strategies based on biotechnological processes or synthetic approaches have been developed. In this scenario the total synthesis can be undoubtedly a useful and powerful tool for obtaining higher amounts of natural products and/or structural modifications thereof. Herein, we emphasize successful examples of total synthesis of galanthamine, morphine, paclitaxel and podophyllotoxin - natural products approved as pharmaceuticals.