Several structurally interesting halogenated chamigrene sesquiterpenes have recently been isolated from the red algal genus Laurencia. Due to the low natural availability, full testing of this family of cytotoxic chamigrenes has been limited. Proposed here is the first enantioselective total synthesis of ma'ilione and its derivatives. The key transformation will involve an asymmetric intramolecular Heck reaction to generate the quaternary carbon stereocenter in high levels of enantioselectivity. The 6,6-spirocyclic all carbon core will result from this cyclization. Development of reaction conditions will be required to achieve desired levels of enantioselectivity during the Heck reaction. Since the remaining stereocenters in the molecule arise from steric control of the quaternary stereocenter, use of a chiral catalyst provides access to both enantiomers of the natural product. The synthetic strategy will allow new chamigrene derivatives to be synthesized from late stage intermediates.
| Gergely, Joshua; Morgan, Jeremy B; Overman, Larry E (2006) Stereocontrolled synthesis of functionalized cis-cyclopentapyrazolidines by 1,3-dipolar cycloaddition reactions of azomethine imines. J Org Chem 71:9144-52 |
