Norstaminane- and isopimarane-type diterpenes of Orthosiphon stamineus from Okinawa

Nine novel highly oxygenated and structurally diverse diterpenes, named norstaminolactone A (), norstaminols B and C ( and ), secoorthosiphols A–C () and orthosiphols R–T () have been isolated from the aerial part of Orthosiphon stamineus cultivated in Okinawa Prefecture, Japan. Norstaminolactone A () is the first representative of a biogenetically unusual norstaminane-type diterpene bearing a nitrogen atom. Norstaminol C () possessed a framework presumed to be biosynthesized from the staminane-type diterpene. Secoorthosiphols A–C () possessed an unprecedented structural feature of the opened ring A system, encountered for the first time in isopimarane-type diterpenes. Secoorothosiphol C () also represents the first example of biogenetically unique and unconventional secoisopimarane-type diterpene bearing a cyano group. Norstaminolactone A () showed a potent antiproliferative activity with an IC50 value of 2.16 μg/mL against highly liver metastatic colon 26-L5 carcinoma cell line.