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.

Automated summary

Clutia lanceolata, a medicinal plant found in Ethiopia, sub-Saharan Africa, and the Arabian Peninsula, is traditionally used in Saudi Arabia for diabetes treatment. Phytochemical analysis of this species previously only identified methylthiocoumarins, but further study has led to the discovery of 19 new diterpenoids in three structural classes. The structures were confirmed through various techniques such as HRMS, NMR, and X-ray crystallography. Some of these compounds, including one closely related to saudin and another with a different core tetracycle, showed strong enhancement of glucose-triggered insulin release in murine pancreatic islets. Biosynthetic proposals for these compounds are also suggested. Lanceolide P (16) is proposed as a lead compound for further development in diabetes treatment.