Oxidative Cleavage and Ring Reconstruction for the Synthesis of Amaryllidaceae Alkaloid Analogues

This study presents the synthesis of analogues of bioactive Amaryllidaceae alkaloids that contain a five-membered ring C and a quaternary carbon centre. The synthesis was carried out in a divergent manner, starting from a common intermediate, keto aldehyde 1 a. This intermediate was obtained by oxidative cleavage of a carbocyclic ring present in the previously synthesised tetracyclic compounds. Subsequent closure of a new heterocyclic ring B using different methods led to products with structural cores found in naturally occurring alkaloids such as pretazettine, tazettine or macronine. In addition, an analogue of egonine was prepared from the same intermediate. Our approach thus provides access to multiple structural types of potentially bioactive molecules. Analogues of bioactive tazettine and mesembrine alkaloids were synthesised from a common keto aldehyde intermediate. The key feature of the synthesis was the reconstruction of the ring B in several different ways to form structural cores of macronine, pretazettine and tazettine. In addition, the same intermediate was used to prepare an egonine-like product.image