SR9009光学异构体的合成及抗衰老作用研究
Synthesis and anti-aging effect of SR9009 optical isomer
吕旭成 1乔学红 2刘嘉榆 3郑润琪 3夏晴 3张维娜 3何新华1
作者信息
- 1. 军事医学研究院毒物药物研究所 北京 100850
- 2. 沈阳药科大学 制药工程学院,辽宁 沈阳 110016
- 3. 军事医学研究院生物医学分析中心 北京 100850
- 折叠
摘要
目的 合成核受体Rev-Erbs受体激动剂SR9009 的光学异构体,并研究其抗衰老活性.方法 以5-硝基噻吩-2-甲醛、对氯苯甲醛、(S)-1-Boc-3-氨甲基吡咯烷或(R)-1-Boc-3-氨甲基吡咯烷等为起始原料,通过还原胺化、脱叔丁氧羰基(t-butyloxy carbonyl,Boc)保护基、酰胺缩合等 4 步,合成SR9009 的光学异构体;并通过秀丽隐杆线虫实验,测试其抗衰老活性.结果 通过4 步反应分别合成了SR9009 光学异构体,(S)-异构体和(R)-异构体的总收率分别为 54.8%和 49.0%;与空白对照相比,(S)-异构体能够显著延长秀丽隐杆线虫的平均寿命 7.8%.结论 首次报道了SR9009 的光学异构体及其合成方法;其(S)-异构体具有较好的抗衰老活性,值得进一步研究.
Abstract
Objective To synthesize and study the anti-aging activity of the optical isomers of SR9009,a nuclear receptor Rev-Erbs agonist.Methods Using 5-nitrothiophene-2-carboxaldehyde,p-chlorobenzaldehyde and(S)-1-Boc-3-aminomethyl pyrrolidine or(R)-1-Boc-3-aminomethyl pyrrolidine as start materials,the optical isomers of SR9009 were synthesized through reductive amination reaction,deprotection of tert-butoxycarbonyl group and amide condensation reaction respectively.And then their anti-aging activities were tested using Caenorhabditis elegans model.Results SR9009 optical isomers were synthesized in four steps,and the total yield of(S)-isomer and(R)-isomer were 54.8%and 49.0%,respectively.In the experiment of C.elegans,(S)-isomer could significantly prolong the average lifespan of C.elegans by 7.8%.Conclusion The optical isomers of SR9009 and their synthetic methods are reported for the first time,and the(S)-isomer has anti-aging activity,which is worthy of further study.
关键词
Rev-Erb/SR9009/光学异构体/合成/抗衰老Key words
Rev-Erb/SR9009/optical isomer/synthesis/anti-aging引用本文复制引用
出版年
2024
NETL
NSTL
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