The leptosins are a class of natural products presenting remarkable molecular complexity and potent cytotoxic and antitumor activity. Thus far, no reports documenting the total synthesis of any of these alkaloids has been published. One of the more complex challenges such a synthesis must address is the stereocontrolled formation of the central bispyrrolidinoindoline ring system containing consecutive all-carbon quaternary centers and two secondary alcohols. It is proposed that using a one-pot double Mukaiyama aldol reaction will allow for the installation of both quaternary centers and adjacent secondary alcohols. Before this reaction can be used to install the above stereogenic centers, it is necessary to understand the stereocontrolling elements of the reaction. With that, before undertaking any total syntheses preliminary studies will focus on examining how varying the structures of the reactive components of the Mukaiyama aldol dictate reaction stereocontrol. Once the stereocontrolling elements of this reaction are understood, a proposal towards completing the total syntheses of leptosins C and K will be presented.
| Dounay, Amy B; Humphreys, Philip G; Overman, Larry E et al. (2008) Total synthesis of the strychnos alkaloid (+)-minfiensine: tandem enantioselective intramolecular Heck-iminium ion cyclization. J Am Chem Soc 130:5368-77 |
| Dounay, Amy B; Overman, Larry E; Wrobleski, Aaron D (2005) Sequential catalytic asymmetric Heck-iminium ion cyclization: enantioselective total synthesis of the Strychnos alkaloid minfiensine. J Am Chem Soc 127:10186-7 |
