Cajanusoids A–D, Unusual Atropisomeric Stilbene Dimers with PTP1B Inhibitory Activities from the Leaves of Cajanus cajan

Four novel stilbene dimers ( 1 – 4 ), together with their biosynthetically related stilbene monomers ( 5 and 6 ), were isolated from the leaves of Cajanus cajan . Their structures with absolute configurations were determined by comprehensive analysis of spectroscopic data and electronic circular dichroism calculations. Compounds 1 and 2 are two novel dimeric stilbenes with an unusual coupling pattern that resulted in a rare configurationally stable Csp 2 –Csp 3 chiral axis with both point and axial chirality in their molecules. Due to their unique inherent structural features, both of them naturally occur as equilibrating mixtures of unequally populated atropo-diastereomers and their respective enantiomers. Compounds 3 and 4 are two pairs of novel dimeric stilbene atropisomers featuring a rotationally hindered central biaryl axis. Notably, 3 contains a rare arylbenzoquinone core and 4 is a symmetric dimer with a C 2 symmetry axis. The hypothetical biosynthetic pathway of 1 – 4 was also proposed herein. All the new compounds exhibited significant protein tyrosine phosphatase-1B (PTP1B) inhibition effects. In addition, the preliminary mode of action for the most potent compound 3 was investigated by molecular docking and binding free energy calculation.