TY - JOUR
T1 - Compounds Related to Saudin and Three New Series of Diterpenoids from Clutia lanceolata
AU - Ahmed, Sarfaraz
AU - Nur-e-Alam, Mohammad
AU - Parveen, Ifat
AU - Threadgill, Michael D.
AU - Orton, James B.
AU - Hafizur, Rahman M.
AU - Khan, Israr
AU - Al-Oqail, Mai
AU - Al-Rehaily, Adnan J.
N1 - 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.
PY - 2023/5/26
Y1 - 2023/5/26
N2 - 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.
AB - 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.
KW - Animals
KW - Diabetes Mellitus
KW - Diterpenes/pharmacology
KW - Insulin
KW - Mice
KW - Molecular Structure
UR - http://www.scopus.com/inward/record.url?scp=85159622068&partnerID=8YFLogxK
U2 - 10.1021/acs.jnatprod.2c00761
DO - 10.1021/acs.jnatprod.2c00761
M3 - Article
C2 - 37128771
SN - 0163-3864
VL - 86
SP - 1129
EP - 1149
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 5
ER -
