Synthesis and evaluation of simplified functionalized bongkrekic acid analogs
Synthesis and evaluation of simplified functionalized bongkrekic acid analogs
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DOI：
10.1016/j.tet.2018.01.018
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发表时间：
2018-03-01
期刊：
影响因子：
2.1
通讯作者：
Shindo, Mitsuru
中科院分区：
文献类型：
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作者：
Fujita, Satoshi;Suyama, Masaki;Shindo, Mitsuru
米酵菌酸（BKA）是腺嘌呤核苷酸转位酶（ANT）的强抑制剂，可抑制三磷酸腺苷的合成。我们设计并合成了简化的含苯环的BKA类似物。关键反应是一锅双Sonogashira反应，它形成了主骨架。类似物在8-10个最长线性序列步骤中有效合成。该合成方法可用于制备具有不同碳链长度组合的其他类似物。此外，苯环上的烯丙氧基可以容易地被其他官能团取代。我们基于线粒体抑制作用的初步生物学评价揭示了具有与BKA相同碳链长度的类似物的高效力。特别地，预官能化的类似物是潜在的ANT抑制剂。(C)2018爱思唯尔有限公司版权所有
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 mitochondria 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. (C) 2018 Elsevier Ltd. All rights reserved.