Synthesis and evaluation of simplified functionalized bongkrekic acid analogs

Satoshi Fujita, Masaki Suyama, Kenji Matsumoto, Atsushi Yamamoto, Takenori Yamamoto, Yuka Hiroshima, Takayuki Iwata, Arihiro Kano, Yasuo Shinohara, Mitsuru Shindo

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)962-969
Number of pages8
JournalTetrahedron
Volume74
Issue number9
DOIs
Publication statusPublished - Mar 1 2018

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Bongkrekic Acid
ATP Translocases Mitochondrial ADP
Benzene
Chain length
Bearings (structural)
Carbon
Skeleton
Functional groups
Adenosine Triphosphate

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

Fujita, S., Suyama, M., Matsumoto, K., Yamamoto, A., Yamamoto, T., Hiroshima, Y., ... Shindo, M. (2018). Synthesis and evaluation of simplified functionalized bongkrekic acid analogs. Tetrahedron, 74(9), 962-969. https://doi.org/10.1016/j.tet.2018.01.018

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.

In: Tetrahedron, Vol. 74, No. 9, 01.03.2018, p. 962-969.

Research output: Contribution to journalArticle

Fujita, S, Suyama, M, Matsumoto, K, Yamamoto, A, Yamamoto, T, Hiroshima, Y, Iwata, T, Kano, A, Shinohara, Y & Shindo, M 2018, 'Synthesis and evaluation of simplified functionalized bongkrekic acid analogs', Tetrahedron, vol. 74, no. 9, pp. 962-969. https://doi.org/10.1016/j.tet.2018.01.018
Fujita S, Suyama M, Matsumoto K, Yamamoto A, Yamamoto T, Hiroshima Y et al. Synthesis and evaluation of simplified functionalized bongkrekic acid analogs. Tetrahedron. 2018 Mar 1;74(9):962-969. https://doi.org/10.1016/j.tet.2018.01.018
Fujita, Satoshi ; Suyama, Masaki ; Matsumoto, Kenji ; Yamamoto, Atsushi ; Yamamoto, Takenori ; Hiroshima, Yuka ; Iwata, Takayuki ; Kano, Arihiro ; Shinohara, Yasuo ; Shindo, Mitsuru. / Synthesis and evaluation of simplified functionalized bongkrekic acid analogs. In: Tetrahedron. 2018 ; Vol. 74, No. 9. pp. 962-969.
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