Herein, we report a concise enantioselective synthesis of (–)-allosecurinine, a tetracyclic
Securinega alkaloid featuring an α,β-unsaturated γ-lactone moiety. Starting from inexpensive
and readily available trans-l-hydroxyproline, our strategy entails a rare late-stage [2+2+1]-hetero-Pauson–Khand
cycloaddition between a ketone and an alkyne as the key complexity-generating step
to rapidly install the CD-ring system. The reported W(CO)6-promoted intramolecular cyclization provides the first example of a tungsten-mediated
hetero-Pauson–Khand reaction. This approach to the strained bicyclic CD motif present
in allosecurinine provides some insights into the boundaries of this potentially
powerful methodology that might be further extended to other butenolide-containing
natural products.
Key words
alkaloids - total synthesis - tungsten - cyclization - natural products
