TY - JOUR
T1 - アデニンヌクレオチド輸送担体(ANT 阻害剤:ボンクレキン酸の合成とその構造展開および生物活性
AU - Shindo, Mitsuru
AU - Iwata, Takayuki
AU - Kano, Arihiro
AU - Shinohara, Yasuo
N1 - Publisher Copyright:
© 2022 Society of Synthetic Organic Chemistry. All rights reserved.
PY - 2022
Y1 - 2022
N2 - Bongkrekic acid(BKA), isolated from the bacterium Burkholderia gladioli, is an inhibitor of adenine nucleotide translocator in the mitochondria inner membrane, and is also a suppressor of apoptosis. Therefore, BKA is an important tool for the investigation of apoptosis as well as mitochondria. Herein, we summarize our total synthesis of BKA and its analogues, and their biological activities. The total synthesis was achieved by employing a three-component convergent strategy based on Julia-Kocienski olefination and Suzuki coupling. Torquoselective olefination with an ynolate was applied for the efficient construction of an unsaturated ester. Based on the total synthesis, various BKA analogues were prepared for structure-activity relationship studies, which indicated that the carboxylic acid moieties were essential for the biological activities of BKA. More readily available BKA analogues with potent biological activity were also developed. A brief summary of the novel biological activities is also provided.
AB - Bongkrekic acid(BKA), isolated from the bacterium Burkholderia gladioli, is an inhibitor of adenine nucleotide translocator in the mitochondria inner membrane, and is also a suppressor of apoptosis. Therefore, BKA is an important tool for the investigation of apoptosis as well as mitochondria. Herein, we summarize our total synthesis of BKA and its analogues, and their biological activities. The total synthesis was achieved by employing a three-component convergent strategy based on Julia-Kocienski olefination and Suzuki coupling. Torquoselective olefination with an ynolate was applied for the efficient construction of an unsaturated ester. Based on the total synthesis, various BKA analogues were prepared for structure-activity relationship studies, which indicated that the carboxylic acid moieties were essential for the biological activities of BKA. More readily available BKA analogues with potent biological activity were also developed. A brief summary of the novel biological activities is also provided.
KW - adenine nucleotide translocator
KW - apoptosis
KW - bongkrekic acid
KW - inhibitors
KW - mitochondria
KW - structure-activity relationship
KW - total synthesis
UR - http://www.scopus.com/inward/record.url?scp=85145884162&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85145884162&partnerID=8YFLogxK
U2 - 10.5059/yukigoseikyokaishi.80.1136
DO - 10.5059/yukigoseikyokaishi.80.1136
M3 - 学術誌
AN - SCOPUS:85145884162
SN - 0037-9980
VL - 80
SP - 1136
EP - 1148
JO - Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
JF - Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
IS - 12
ER -