Chemical and Antiplasmodial Investigations on -Derived Alkaloids and Semisynthetic Ether Analogues.

Microthecaline A (), the known antiplasmodial quinoline serrulatane alkaloid from the roots of F. Muell. ex Benth. (Scrophulariaceae), was targeted for isolation and subsequent use in the generation of a semisynthetic ether library. A large-scale extraction and isolation yielded the previously undescribed quinoline serrulatane microthecaline B (), along with crystalline that enabled the first X-ray crystallographic analysis to be undertaken on this rare alkaloid structure class. The X-ray diffraction analysis of supported the absolute configuration assignment of microthecaline A, which was originally assigned by ECD data analysis. Microthecaline A () was converted into 10 new semisynthetic ether derivatives (-) using a diverse series of commercially available alkyl halides. Chemical structures of the new serrulatane alkaloid and semisynthetic ether analogues were assigned by spectroscopic and spectrometric analyses. Antiplasmodial evaluations of - showed that the semisynthetic derivative elicited the most potent activity with an IC value of 7.2 μM against 3D7 (drug-sensitive) strain.