A versatile approach to 1-oxo-, 1-oxo-3,4-dihydro- and 1,3,4-trioxo isoquinoline alkaloids and first total synthesis of the dimeric 1-oxoisoquinoline alkaloids berbanine and berbidine

Abstract

We have worked out a very short approach to 1-oxoisoquinoline alkaloids starting from readily available 2-bromobenzamides utilizing a 2-ethoxyvinylboronate as a C2 building block for introduction of the C-3,C-4 unit of the isoquinoline core. TFA-mediated cyclization of crude ortho-ethoxyvinyl benzamides gave 1-oxoisoquinolines in one single operation. Further modifications of these compounds opened an access to the other chemotypes. In total, 14 alkaloids from four chemotypes (five 1-oxoisoquinolines, six 1-oxo-3,4-dihydroisoquinolines, one 1,3,4-trioxoisoquinoline, and two dimeric isoquinoline alkaloids) were obtained in this investigation. With this approach we improved the total syntheses of the monomeric oxoisoquinolines, and worked out the first total syntheses of the dimeric alkaloids berbanine and berbidine.