Natural product-based synthesis of novel anti-infective isothiocyanate- and isoselenocyanate-functionalized amphilectane diterpenes

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• 作者：Karinel Nieves^a ; Jacques Prudhomme^b ; Karine G. Le Roch^b ; Scott G. Franzblau^c ; Abimael D. Rodrí ; guez^a ; ^{abimael.rodriguez1@upr.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Malaria ; Tuberculosis ; Isothiocyanate ; Isoselenocyanate ; Isocyanide ; Synthesis of natural product derivatives
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：1 February 2016
• 年：2016
• 卷：26
• 期：3
• 页码：854-857
• 全文大小：434 K

文摘

The marine natural product (−)-8,15-diisocyano-11(20)-amphilectene (1), isolated from the Caribbean sponge Svenzea flava, was used as scaffold to synthetize five new products, all of which were tested against laboratory strains of Plasmodium falciparum and Mycobacterium tuberculosis H₃₇Rv. The scaffold contains two isocyanide units that are amenable to chemical manipulation, enabling them to be elaborated into a small library of sulfur and selenium compounds. Although most of the analogs prepared were less potent than the parent compound, 5 was nearly equipotent showing IC₅₀ values of 0.0066 μM and 0.0025 μM, respectively, against two strains (Dd2 and 3D7) of the malaria parasite. On the other hand, when assayed against the tuberculosis bacterium, analogs 5 and 6 were found to be more potent than 1.