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Isolation, structure elucidation and PTP1B inhibitory activity of serrulatane diterpenoids from the roots of Myoporum insulare
Phytochemistry Letters ( IF 1.3 ) Pub Date : 2020-07-17 , DOI: 10.1016/j.phytol.2020.07.001
Louise Kjaerulff , Alexander Baekager Just Jensen , Chi Ndi , Susan Semple , Birger Lindberg Møller , Dan Staerk

A methylene chloride extract of Myoporum insulare R. Br. (Scrophulariaceae) root material was investigated by dual high-resolution PTP1B/α-glucosidase inhibition profiling and LC-PDA-HRMS. Subsequent analytical-scale separation of the crude extract afforded serrulatanes 1-9 of which 2 ((1R,11S,18R)-5,18-epoxyserrulat-3,14-dien-8,18-diol or myoporulatane A), 6 ((1R,4S,11S)-8-hydroxy-serrulat-14-en-18,5-olide or myoporulatane B), 7 ((1R,4S,11S)-serrulat-14-en-5,8,18-trione or myoporulatane C), and 9 ((1S, 2R,4S,11S)-2β-hydroxy-serrulat-14-ene or myoporulatane D) are previously unreported. The structures of all isolated compounds were established by HRMS as well as 1D and 2D NMR analysis. Relative configurations were determined from combined analyses of chemical shifts, J-coupling constants and ROESY correlations, and absolute configurations were tentatively assigned by comparison to previous studies and from biosynthetic arguments. Compounds correlated with PTP1B inhibitory activity in the high-resolution inhibition profile were tested after isolation. However, the pure compounds exhibited weak or essentially no inhibitory activity against PTP1B with IC50 values of 97.4 μM for 2, 3.0 mM for 4, and > 100 μM for 7. This is the first study of the root chemistry of M. insulare.



中文翻译:

岛爪哇麦根根中拟南芥二萜类化合物的分离,结构鉴定和PTP1B抑制活性

Myoporum insulare R. Br。的二氯甲烷萃取物。通过双重高分辨率PTP1B /α-葡萄糖苷酶抑制谱和LC-PDA-HRMS研究了(玄参)根材料。粗提取物的随后的分析规模分离,得到serrulatanes 1 - 9其中2((1 - [R,11小号,18 - [R)-5,18-epoxyserrulat -3,14-二烯8,18二醇或myoporulatane A) ,6(((1 R,4 S,11 S)-8-羟基-serrulat-14-en-18,5-olide或myoporulatane B),7((1 R,4 S,11 S)-serrulat-14-en-5,8,18-trione或myoporulatane C)和9((1 S,2 R,4 S,11 S)-2β-羟基-serrulat-14-ene或myoporulatane D)以前未报告。通过HRMS以及1D和2D NMR分析确定所有分离的化合物的结构。相对构型是通过化学位移J的综合分析确定的通过与先前研究的比较以及来自生物合成论证,初步确定了偶联常数和ROESY相关性以及绝对构型。分离后测试高分辨率抑制曲线中与PTP1B抑制活性相关的化合物。但是,纯化合物对PTP1B表现出微弱或基本没有抑制活性,IC 50值分别为2的97.4μM ,4的3.0 mM和7的> 100μM 。这是对岛楠根化学的首次研究。

更新日期:2020-07-17
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