6 research outputs found
Total Synthesis of Lepadiformine Alkaloids using <i>N</i>-Boc α-Amino Nitriles as Trianion Synthons
Lepadiformine A, B, and C were synthesized in an enantiomerically
pure form using a reductive cyclization strategy. <i>N</i>-Boc α-amino nitriles were deprotonated and alkylated with
enantiomerically pure dibromides to afford the first ring. The products
were manipulated to introduce phosphate leaving groups, and subsequent
reductive lithiation followed by intramolecular alkylation formed
the second ring with high stereoselectivity. The third ring was formed
by intramolecular displacement of a mesylate by the deprotected amine.
Lepadiformine A and B contain a hydroxymethyl group adjacent to the
amine. This appendage was introduced in a sequence using a Polonovski–Potier
reaction as the key step. The synthetic strategy is stereoselective
and convergent and demonstrates the utility of <i>N</i>-Boc
α-amino nitriles as linchpins for alkaloid synthesis