General strategies for the stereoselective synthesis of alkaloid natural products

Abstract

We have recently discovered that vinylogous Mannich reactions are powerful strategy-level reactions for the construction of skeletal subunits common to a variety of alkaloids. Such reactions have been implemented in tandem with hetero Diels-Alder reactions for the synthesis of the representative heteroyohimboid alkaloid tetrahydroalstonine (4). One of the intermediates in the synthesis of 4 was then converted into 6, which was subjected to a novel, biogenetically-patterned oxidative reorganization to give the Strychnos alkaloid akuammacine (10). Both bimolecular and intramolecular vinylogous Mannich reactions have been applied to the syntheses of the Ergot alkaloids rugulovasines A and B (21 and 22, respectively), and two consecutive bimolecular vinylogous Mannich reactions of furans have been implemented for the rapid assembly of a tetracyclic intermediate in an asymmetric total synthesis of croomine (40).