Bioinspired Syntheses of the Marine Pyridoacridine Alkaloids 2-Bromo and 3-Bromodeoxyamphimedine and Structure Correction of 2-Bromoamphimedine

Abstract

We have used an efficient bioinspired methodology to synthesize, for the first time, the recently reported antibacterial brominated pyridoacridine alkaloids 2-bromodeoxyamphimedine and 3-bromodeoxyamphimedine. The synthetic route started with the synthesis of 5-bromo and 6-bromokynuramine, the latter being a sponge-derived marine natural product. Oxidative addition of the brominated kynuramine analogues, with Boc-dopamine, afforded the anticipated natural products 2- and 3-bromostyelsamine D. Further 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 of 2-bromodeoxyamphimedine and 3-bromodeoxyamphimedine using K₃[Fe(CN)₆] gave 2- and 3-bromoamphimedine, respectively. ¹H NMR data reported for ‘2-bromoamphimedine’, isolated from a Petrosia n. sp. sponge differed from the data observed for synthetic 2-bromoaphimedine but were in good agreement with those observed for synthetic 3-bromoamphimedine, requiring structure correction of the isolated natural product.