Synthesis of the Potent Anticancer Agents Ottelione A and Ottelione B in Both Racemic and Natural Optically Pure Forms

The powerful antitumor agents ottelione A and B were synthesized in racemic form by a method that relies on selective ring closing metathesis. Optically pure natural (+)-ottelione A was then made from d-ribose, via an α-keto cyclopropane. A key feature of the route is that the cyclopropyl group controls the stereochemistry in the attachment of the ArCH2 unit and is then converted by the action of SmI2 into a vinyl group, so that the substituents on the resulting five-membered ring have the required trans relationship. Epimerization of an intermediate gave access by the same method to the trans ring fused isomer (−)-ottelione B.