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

作　　者：吕旭成 乔学红 刘嘉榆 郑润琪 夏晴 张维娜 何新华 LYU Xucheng;QIAO Xuehong;LIU Jiayu;ZHENG Runqi;XIA Qing;ZHANG Weina;HE Xinhua(Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China;School of Pharmaceutical Engineering,Shenyang Pharmaceutical University,Shenyang 110016,China;National Center for Biomedical Analysis,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China)

机构地区：[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

出　　处：《沈阳药科大学学报》2024年第6期712-719,725,共9页Journal of Shenyang Pharmaceutical University

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。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 

分 类 号：R914[医药卫生—药物化学]