Total synthesis of (+/-)-nudenoic acid.

In 1968, Marshall and Johnson settled a long-standing structural problem with â-vetivone, firmly establishing it as 1 by synthesis.1 Previously, â-vetivone was considered to be a bicyclic R,â-unsaturated ketone possessing a hydrazulene framework, interpretive of its dehydrogenation to give vetivazulene. The interpretive error arose from the assumption that the dehydrogenation occurred without skeletal rearrangement. It is interesting that after 28 years sesquiterpenes having a skeleton which is directly descendant of the spirovetivanes were isolated. A member of the new tricyclic sesquiterpenes, nudenoic acid (2), is elaborated by the liverwort Mylia nuda, which is indigenous to Taiwan.2 On examination of the molecular constitution (absolute configuration unknown) one can readily surmise a close relationship of nudenoic acid with the spirovetivanes, particularly hinesol 3. Thus, it is conceivable that acid 4, an oxidized derivative of hinesol, undergoes cyclization in vivo to generate 2. The occurrence of spirovetivanes in several liverworts3-5 lends support to this speculation.