Parameters for bromination of pyrroles in bromoperoxidase-catalyzed oxidations

Ester-, cyano-, and carboxamide-substituted 1 H-pyrroles undergo electrophilic aromatic bromination, if treated with hydrogen peroxide and sodium bromide at pH 6.2 and 20 °C. Oxidation of bromide under such conditions is catalyzed by a vanadate(V)-dependent bromoperoxidase, in a substrate/enzyme ratio of 32–63 μmol %. To obtain maximum yields of bromopyrroles (up to 91%) by spending least amount of substrates and catalyst, hydrogen peroxide and sodium bromide have to be added continuously to the enzyme and the 2-acceptor-substituted pyrrole (1.5 mmol) in a solution of morpholine-4-ethanesulfonic acid buffer. This technique was applied to prepare two marine natural products under biomimetic conditions, that is, methyl 4,5-dibromopyrrole-2-carboxylate (from Agelas oroides) and 4,5-dibromopyrrole-2-carboxamide (from Acanthella carteri). [Display omitted]