Compounds related to saudin and three new series of diterpenoids from clutia lanceolata
Compounds related to saudin and three new series of diterpenoids from clutia lanceolata
Clutia lanceolata is a medicinal plant native to Ethiopia and sub-Saharan Africa and to the Arabian Peninsula. It is used traditionally in Saudi Arabia for the treatment of diabetes. Previous phytochemical analysis of this species has been limited to the identification of methylthiocoumarins. Further work has led to isolation of 19 new diterpenoids in three structural classes. Their structures were established by HRMS and by a range of NMR techniques (1H, 13C, COSY, NOESY, HSQC, HMBC), with confirmation for some examples by X-ray crystallography. NOESY and 1H–1H NMR coupling constants gave the relative stereochemical configurations and conformational information, with absolute configurations being established through X-ray crystallography. One example closely related to the known hypoglycemic compound saudin (found in C. richardiana and also in C. lanceolata) and one with a different core tetracycle were found to enhance strongly the glucose-triggered release of insulin from murine pancreatic islets. Biosynthetic proposals for the three groups of new diterpenoids by alternative cyclization of a common precursor are put forward. Lanceolide P (16) is proposed as a lead compound for further development for the treatment of diabetes.
1129–1149
Ahmed, Sarfaraz M.
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Nur-e-Alam, Mohammad
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Parveen, Ifat
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Threadgill, Michael D.
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Orton, James
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Hafizur, Rahman M.
01b715fb-41dc-419c-ae93-d842aa17babf
Khan, Israr
8b39aa07-37fc-486f-8384-329f38cf7a5b
Al-Oqail, Mai
afbffa9c-ff1d-44f8-9b20-496b6cd21ae4
Al-Rehaily, Adnan J.
1e86082e-959c-4412-802b-a8265e475fe1
2 May 2023
Ahmed, Sarfaraz M.
20e27953-71d2-401f-b632-73d42e2e1629
Nur-e-Alam, Mohammad
32b7b448-599c-4918-ab9e-fefdb848293a
Parveen, Ifat
7839b403-8949-4b72-ac84-840c07561b11
Threadgill, Michael D.
46157754-27f0-468a-9714-70803ef609c4
Orton, James
4e2a471f-9e11-4cb4-abb6-d0398047939f
Hafizur, Rahman M.
01b715fb-41dc-419c-ae93-d842aa17babf
Khan, Israr
8b39aa07-37fc-486f-8384-329f38cf7a5b
Al-Oqail, Mai
afbffa9c-ff1d-44f8-9b20-496b6cd21ae4
Al-Rehaily, Adnan J.
1e86082e-959c-4412-802b-a8265e475fe1
Ahmed, Sarfaraz M., Nur-e-Alam, Mohammad, Parveen, Ifat, Threadgill, Michael D., Orton, James, Hafizur, Rahman M., Khan, Israr, Al-Oqail, Mai and Al-Rehaily, Adnan J.
(2023)
Compounds related to saudin and three new series of diterpenoids from clutia lanceolata.
Journal of Natural Products, 86 (5), .
(doi:10.1021/acs.jnatprod.2c00761).
Abstract
Clutia lanceolata is a medicinal plant native to Ethiopia and sub-Saharan Africa and to the Arabian Peninsula. It is used traditionally in Saudi Arabia for the treatment of diabetes. Previous phytochemical analysis of this species has been limited to the identification of methylthiocoumarins. Further work has led to isolation of 19 new diterpenoids in three structural classes. Their structures were established by HRMS and by a range of NMR techniques (1H, 13C, COSY, NOESY, HSQC, HMBC), with confirmation for some examples by X-ray crystallography. NOESY and 1H–1H NMR coupling constants gave the relative stereochemical configurations and conformational information, with absolute configurations being established through X-ray crystallography. One example closely related to the known hypoglycemic compound saudin (found in C. richardiana and also in C. lanceolata) and one with a different core tetracycle were found to enhance strongly the glucose-triggered release of insulin from murine pancreatic islets. Biosynthetic proposals for the three groups of new diterpenoids by alternative cyclization of a common precursor are put forward. Lanceolide P (16) is proposed as a lead compound for further development for the treatment of diabetes.
Text
Revised revised revised JNP manuscript D
- Accepted Manuscript
More information
Accepted/In Press date: 2 May 2023
e-pub ahead of print date: 2 May 2023
Published date: 2 May 2023
Additional Information:
Funding Information:
The authors extend their appreciation to Researchers Supporting Project number (RSP2023R380), King Saud University, Riyadh, Saudi Arabia, for funding this work. We are thankful for support from BEACON Plus (grant EDRF 80851) from the European Regional Development Fund through the Welsh European Funding Office, part of the Welsh Assembly, and to Aberystwyth University. We also thank Helen C. Phillips (Aberystwyth University) for providing many of the mass spectra.
Publisher Copyright:
© 2023 American Chemical Society and American Society of Pharmacognosy.
Identifiers
Local EPrints ID: 477279
URI: http://eprints.soton.ac.uk/id/eprint/477279
ISSN: 0163-3864
PURE UUID: 4a1ceb04-be63-428b-84f4-dca369e9b037
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Date deposited: 02 Jun 2023 16:31
Last modified: 02 May 2024 04:01
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Contributors
Author:
Sarfaraz M. Ahmed
Author:
Mohammad Nur-e-Alam
Author:
Ifat Parveen
Author:
Michael D. Threadgill
Author:
James Orton
Author:
Rahman M. Hafizur
Author:
Israr Khan
Author:
Mai Al-Oqail
Author:
Adnan J. Al-Rehaily
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