Synthesis of 2-bromo and 3-bromo deoxyamphimedines and amphimedines

The antibacterial brominated pyridoacridine alkaloids 2-bromodeoxyamphimedine and 3-bromodeoxyamphimedine have been synthesized using a bioinspired methodology. Synthetic precursors were 5-bromo and 6-bromokynuramine, the latter being a sponge-derived marine natural product. Two-step oxidative addition followed by Pictet-Spengler reaction with paraformaldehyde afforded the target brominated deoxyamphimedines, spectroscopic data for which were in excellent agreement with those reported for the isolated natural products. Oxidation using K3[Fe(CN)6] gave 2- and 3-bromoamphimedine, respectively. Comparison of 1H NMR data with those reported for ‘2-bromoamphimedine’ (a natural product isolated from a Petrosia n. sp. sponge) indicated that the structure of the natural product should be corrected to the 3-bromo isomer.