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Synthesis and evaluation of simplified functionalized bongkrekic acid analogs
- Fujita, Satoshi, Suyama, Masaki, Matsumoto, Kenji, Yamamoto, Atsushi, Yamamoto, Takenori, Hiroshima, Yuka, Iwata, Takayuki, Kano, Arihiro, Shinohara, Yasuo, Shindo, Mitsuru
- Tetrahedron 2018 v.74 no.9 pp. 962-969
- adenosine triphosphate, benzene, carbon, chemical reactions, enzymes, mitochondria, moieties
- Bongkrekic acid (BKA) is a strong inhibitor of adenine nucleotide translocase (ANT), inducing inhibition of adenosine triphosphate synthesis. We designed and synthesized simplified benzene-ring-containing BKA analogs. The key reaction is the one-pot double Sonogashira reaction, which forms the main skeleton. The analogs were efficiently synthesized in 8–10 longest linear sequence steps. This synthetic method can be applied for the preparation of other analogs having different combinations of carbon chain lengths. Furthermore, the allyloxy group on the benzene ring can be easily replaced by other functional groups. Our preliminary biological evaluation based on mitochondrial inhibitory effects revealed the high potency of the analogs bearing the same carbon chain length as that of BKA. In particular, the prefunctionalized analogs are potential ANT inhibitors.