? A novel methodology for the synthesis of important bicyclic and polycyclic ring systems is proposed, along with its application to a natural product synthesis. The method includes a vinylogous Morita-Baylis-Hillman reaction and subsequent aldol condensation, performed in a single step and using a single catalyst. The significance of this method will then be demonstrated in the synthesis of the pentacyclic triterpene portion of QS-21, a potent cancer and HIV vaccine adjuvant. The synthetic strategy involves the proposed method in an elegant cyclization step, which should generate three of the five ring systems in a single step. While time constraints of a two-year postdoctoral appointment will not allow synthesis of the entirety of QS-21 by the applicant, it is anticipated that the sponsor's group may ultimately complete the total synthesis of this molecule using their glycoside methodology. In addition to contributing to the limited literature on the synthesis of the structurally complex pentacyclic triterpenes, a total synthesis of this important molecule would provide sufficient material necessary for extensive biological investigations. ? ?
| Thalji, Reema K; Roush, William R (2005) Remarkable phosphine-effect on the intramolecular aldol reactions of unsaturated 1,5-diketones: highly regioselective synthesis of cross-conjugated dienones. J Am Chem Soc 127:16778-9 |
