Functionalization of 4-bromobenzo[ c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

Benedikt C Melzer; Alois Plodek; Franz Bracher

doi:10.3762/bjoc.15.222

Functionalization of 4-bromobenzo[ c][2,7]naphthyridine via regioselective direct ring metalation. A novel approach to analogues of pyridoacridine alkaloids

Beilstein J Org Chem. 2019 Sep 26:15:2304-2310. doi: 10.3762/bjoc.15.222. eCollection 2019.

Authors

Benedikt C Melzer¹, Alois Plodek¹, Franz Bracher¹

Affiliation

¹ Department of Pharmacy - Center for Drug Research, Ludwig-Maximilians University Munich, Butenandtstr. 5-13, 81377 Munich, Germany.

Abstract

Readily available 4-bromobenzo[c][2,7]naphthyridine undergoes regioselective direct ring metalation at C-5 with TMPMgCl∙LiCl at -40 °C. Quenching with various electrophiles gives a broad range of 5-substituted products, which are building blocks for the synthesis of heterocyclic natural products and analogues thereof. In combination with a Parham-type cyclization a novel approach to pyrido[4,3,2-mn]acridones has been worked out.

Keywords: alkaloids; cyclization; metalation; naphthyridine; pyridoacridine.