Conformational Analysis of Diterpene Lactone Andrographolide towards Reestablishment of Its Absolute Configuration via Theoretical and Experimental ECD and VCD Methods

Andrographolide, the major constituent from the terrestrial plant Andrographis paniculata is a much-studied bioactive ent-labdane diterpene lactone and has become an important medicinal intermediate. Its structure as determined by X-ray crystallography has been applied in molecular docking studies t...

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Autores principales:	Muhamad Faid A Kadir, Agustono Wibowo, Fatimah Salim, El Hassane Anouar, Khalijah Awang, Moses Kiprotich Langat, Rohaya Ahmad
Formato:	article
Lenguaje:	EN
Publicado:	Department of Chemistry, Universitas Gadjah Mada 2020
Materias:	andrographolide conformational analysis exciton coupling vibrational circular dichroism absolute configuration Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/93960032e2564071babd6ec9f5cba905
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spelling	oai:doaj.org-article:93960032e2564071babd6ec9f5cba9052021-12-02T13:24:41ZConformational Analysis of Diterpene Lactone Andrographolide towards Reestablishment of Its Absolute Configuration via Theoretical and Experimental ECD and VCD Methods1411-94202460-157810.22146/ijc.55206https://doaj.org/article/93960032e2564071babd6ec9f5cba9052020-12-01T00:00:00Zhttps://jurnal.ugm.ac.id/ijc/article/view/55206https://doaj.org/toc/1411-9420https://doaj.org/toc/2460-1578Andrographolide, the major constituent from the terrestrial plant Andrographis paniculata is a much-studied bioactive ent-labdane diterpene lactone and has become an important medicinal intermediate. Its structure as determined by X-ray crystallography has been applied in molecular docking studies to explain biological activities. Nevertheless, recently there has been a number of conflicting reports concerning the stereochemistry at the C-14 and C-10 positions affecting the absolute configuration (AC) of the compound. Since a lack of information on the molecular flexibility of the molecule can lead to misleading conclusions on biological activity, a conformational analysis of the molecule in the solution state was necessary. The conformational analysis was performed by the Spartan14 package using the Merck Molecular Force Field (MMFF). The exciton chirality method in electronic circular dichroism spectroscopy (ECM-ECD) and vibrational circular dichroism (VCD) techniques were then jointly employed to re-establish the AC of andrographolide. Theoretical calculations were performed using TD-DFT methods by using the hybrid functionals B3LYP and CAM-B3LYP combined with 6-31G(d,p) basis set. Long-range exciton coupling of 2-naphthoyl chromophores at C-14 and C-19 led to the establishment of the AC to be 3R, 4R, 5S, 9R, 10R and 14S. Comparison between the theoretical VCD data of 14-S and 14-R stereoisomer confirmed a configuration of S at C-14 position instead of R.Muhamad Faid A KadirAgustono WibowoFatimah SalimEl Hassane AnouarKhalijah AwangMoses Kiprotich LangatRohaya AhmadDepartment of Chemistry, Universitas Gadjah Madaarticleandrographolideconformational analysisexciton couplingvibrational circular dichroismabsolute configurationChemistryQD1-999ENIndonesian Journal of Chemistry, Vol 21, Iss 1, Pp 148-156 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	andrographolide conformational analysis exciton coupling vibrational circular dichroism absolute configuration Chemistry QD1-999
spellingShingle	andrographolide conformational analysis exciton coupling vibrational circular dichroism absolute configuration Chemistry QD1-999 Muhamad Faid A Kadir Agustono Wibowo Fatimah Salim El Hassane Anouar Khalijah Awang Moses Kiprotich Langat Rohaya Ahmad Conformational Analysis of Diterpene Lactone Andrographolide towards Reestablishment of Its Absolute Configuration via Theoretical and Experimental ECD and VCD Methods
description	Andrographolide, the major constituent from the terrestrial plant Andrographis paniculata is a much-studied bioactive ent-labdane diterpene lactone and has become an important medicinal intermediate. Its structure as determined by X-ray crystallography has been applied in molecular docking studies to explain biological activities. Nevertheless, recently there has been a number of conflicting reports concerning the stereochemistry at the C-14 and C-10 positions affecting the absolute configuration (AC) of the compound. Since a lack of information on the molecular flexibility of the molecule can lead to misleading conclusions on biological activity, a conformational analysis of the molecule in the solution state was necessary. The conformational analysis was performed by the Spartan14 package using the Merck Molecular Force Field (MMFF). The exciton chirality method in electronic circular dichroism spectroscopy (ECM-ECD) and vibrational circular dichroism (VCD) techniques were then jointly employed to re-establish the AC of andrographolide. Theoretical calculations were performed using TD-DFT methods by using the hybrid functionals B3LYP and CAM-B3LYP combined with 6-31G(d,p) basis set. Long-range exciton coupling of 2-naphthoyl chromophores at C-14 and C-19 led to the establishment of the AC to be 3R, 4R, 5S, 9R, 10R and 14S. Comparison between the theoretical VCD data of 14-S and 14-R stereoisomer confirmed a configuration of S at C-14 position instead of R.
format	article
author	Muhamad Faid A Kadir Agustono Wibowo Fatimah Salim El Hassane Anouar Khalijah Awang Moses Kiprotich Langat Rohaya Ahmad
author_facet	Muhamad Faid A Kadir Agustono Wibowo Fatimah Salim El Hassane Anouar Khalijah Awang Moses Kiprotich Langat Rohaya Ahmad
author_sort	Muhamad Faid A Kadir
title	Conformational Analysis of Diterpene Lactone Andrographolide towards Reestablishment of Its Absolute Configuration via Theoretical and Experimental ECD and VCD Methods
title_short	Conformational Analysis of Diterpene Lactone Andrographolide towards Reestablishment of Its Absolute Configuration via Theoretical and Experimental ECD and VCD Methods
title_full	Conformational Analysis of Diterpene Lactone Andrographolide towards Reestablishment of Its Absolute Configuration via Theoretical and Experimental ECD and VCD Methods
title_fullStr	Conformational Analysis of Diterpene Lactone Andrographolide towards Reestablishment of Its Absolute Configuration via Theoretical and Experimental ECD and VCD Methods
title_full_unstemmed	Conformational Analysis of Diterpene Lactone Andrographolide towards Reestablishment of Its Absolute Configuration via Theoretical and Experimental ECD and VCD Methods
title_sort	conformational analysis of diterpene lactone andrographolide towards reestablishment of its absolute configuration via theoretical and experimental ecd and vcd methods
publisher	Department of Chemistry, Universitas Gadjah Mada
publishDate	2020
url	https://doaj.org/article/93960032e2564071babd6ec9f5cba905
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Conformational Analysis of Diterpene Lactone Andrographolide towards Reestablishment of Its Absolute Configuration via Theoretical and Experimental ECD and VCD Methods

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