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 alpha-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.
Clive
Derrick L J
DL
Chemistry Department, University of Alberta, Edmonton, Alberta T6G 2G2, Canada. derrick.clive@ualberta.ca
Liu
Dazhan
D
D000447:Aldehydes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D003512:Cyclohexanones / Q000138:chemical synthesis* / Q000737:chemistry; D003521:Cyclopropanes / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
D000447:Aldehydes; D000970:Antineoplastic Agents; D001688:Biological Products; D003512:Cyclohexanones; D003521:Cyclopropanes; C468748:ottelione A; C468747:ottelione B; C030797:cyclopropane