TY - JOUR
T1 - Stable Axially Chiral Isomers of Arylnaphthalene Lignan Glycosides with Antiviral Potential Discovered from Justicia procumbens
AU - Zhao, Yang
AU - Ku, Chuen-Fai
AU - Xu, Xin-Ya
AU - Tsang, Nga-Yi
AU - Zhu, Yu
AU - Zhao, Chen-Liang
AU - Liu, Kang-Lun
AU - Li, Chuang-Chuang
AU - Rong, Lijun
AU - Zhang, Hong-Jie
N1 - Funding Information:
The work described in this paper was supported by the Research Grant Council of the Hong Kong Special Administrative Region, China (Projects No. HKBU 12103618 and 12103917), the Innovation and Technology Commission of Hong Kong Special Administrative Region, China (MHP/105/19), and the Hong Kong Scholars Program Foundation (NO. XJ2017058). We are grateful to Dr. Liu Kai from Institute of Marine Drugs, Guangxi University of Chinese Medicine, for assistance with the ECD calculations and Professor Pei-Yuan Yu, Department of Chemistry, Southern University of Science and Technology, for assistance with the calculation of the barriers between the two atropisomers.
Publisher Copyright:
© 2021 American Chemical Society. All rights reserved.
PY - 2021/4/16
Y1 - 2021/4/16
N2 - Arylnaphthalene lignans (ANLs) were known to have axial chirality due to the biphenyl skeleton with hindered rotation at the single bond. However, the stable ANL atropisomers have not been isolated from nature until the present study. Phytochemical separation of the methanol extract of the stems and barks of Justicia procumbens led to the isolation of 11 ANL glycosides including four pairs of new atropisomers with stable confirmations at room temperature. Their structures were deduced from elucidation of the extensive spectral data, and their absolute configurations were determined by the circular dichroism, electronic circular dichroism, and X-ray methods as well as the total synthesis of one pair of the atropisomers. The ANL compounds were evaluated for their antiviral potential, and it was found that they displayed great antiviral activity discrepancy between a pair of atropisomers due to the geometric orientation. The 1′P-oriented atropisomers showed much more significant antiviral potency than their corresponding 1′M-oriented counterparts. The biological activity discrepancy caused by the axial chirality will not only inspire synthetic design of novel ANL atropisomers to enrich the structural diversity, but also provide important hints to direct the synthetic approaches toward the antiviral drug development of ANL compounds.
AB - Arylnaphthalene lignans (ANLs) were known to have axial chirality due to the biphenyl skeleton with hindered rotation at the single bond. However, the stable ANL atropisomers have not been isolated from nature until the present study. Phytochemical separation of the methanol extract of the stems and barks of Justicia procumbens led to the isolation of 11 ANL glycosides including four pairs of new atropisomers with stable confirmations at room temperature. Their structures were deduced from elucidation of the extensive spectral data, and their absolute configurations were determined by the circular dichroism, electronic circular dichroism, and X-ray methods as well as the total synthesis of one pair of the atropisomers. The ANL compounds were evaluated for their antiviral potential, and it was found that they displayed great antiviral activity discrepancy between a pair of atropisomers due to the geometric orientation. The 1′P-oriented atropisomers showed much more significant antiviral potency than their corresponding 1′M-oriented counterparts. The biological activity discrepancy caused by the axial chirality will not only inspire synthetic design of novel ANL atropisomers to enrich the structural diversity, but also provide important hints to direct the synthetic approaches toward the antiviral drug development of ANL compounds.
UR - http://www.scopus.com/inward/record.url?scp=85105041372&partnerID=8YFLogxK
U2 - 10.1021/acs.joc.1c00068
DO - 10.1021/acs.joc.1c00068
M3 - Article
AN - SCOPUS:85105041372
VL - 86
SP - 5568
EP - 5583
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
SN - 0022-3263
IS - 8
ER -