Synthesis of aminal-type Lilium candidum alkaloids and lilaline; determination of their relative configuration by the concerted use of NMR spectroscopy and DFT conformational analysis

Abstract

Abstract We hereby report the synthesis of six racemic alkaloids isolated from Lilium candidum L. Their common structural feature is a five-membered lactam ring which is, in the case of the flavonoid alkaloid lilaline, attached to the molecule’s aromatic core, while in the case of the other five compounds, it is connected to the nitrogen atom of a pyrrolinone ring by an aminal function. The syntheses of these natural products were achieved via Mannich-type alkylations through cyclic N-acyliminium ions as intermediates. Besides the synthesis, the so far unexplored stereochemistry of these natural products was determined by a combination of NMR-based proton–proton distance measurements and theoretical conformational analyses carried out at the DFT level.