Pteridic acid A

The total synthesis of pteridic acids A and B is reported. The convergent asymmetric synthesis involved the use of a diastereoselective ethyl ketone aldol reaction followed by an efficient spiroketalization and provided pteridic acids A and B in 2.9% and 2.8% overall yield, respectively.

The present study aimed at identifying cell cycle inhibitors from the fermentation broth of Streptomyces pseudoverticillus YN17707. Activity-guided isolation was performed on tsFT210 cells. Compounds were isolated through various chromatographic methods and elucidated by spectroscopic analyses. Flow cytometry was used to evaluate the cell cycle inhibitory activities of the fractions and compounds. Two compounds were obtained and identified as pteridic acid hydrate (1) and pteridic acid C (2), which arrested the tsFT210 cells at the G0/G1 phase with the MIC values being 32.8 and 68.9 μmol·L(-1), respectively. These results provide a basis for future development of Compounds 1 and 2 as novel cell cycle inhibitors for cancer therapy.

A convergent approach to the total synthesis of pteridic acid A, having potent plant growth regulator activity, is described. Key steps include the desymmetrization of bicyclic olefin with Brown's chiral hydroboration, acid-mediated spiroketalization, and zirconium-catalyzed ethylmagnesation protocol to install the ethyl stereocenter at C14.