Highly Efficient, Enantioselective Total Synthesis of the Active Anti-Influenza A Virus Indole Alkaloid Hirsutine and Related Compounds by Domino Reactions

Abstract

A very short reaction sequence consisting of a domino Knoevenagel/hetero-Diels-Alder reaction with subsequent solvolysis and hydrogenation, provides the indole alkaloid hirsutine, which greatly inhibits the growth of influenza A viruses, and related compounds in enantiomerically pure form (see reaction scheme). The facial differentiation of the cycloaddition can be reversed by simple variation of the substituents on the indole nitrogen atom (H/tBuOCO). Cbz=benzyloxycarbonyl.