Total Synthesis of Murrastifoline-A by Way of the Pd-catalyzed Double N-Arylation of a Carbazolamine with a 2,2’-Dibromobiphenyl Derivative

The first total synthesis of murrastifoline-A (1), a biscarbazole alkaloid is described.The biscarbazole skeleton of 1 was effectively constructed by the Pd-catalyzed double N-arylation of carbazolamine (bottomhalf segment, 3) with dibromobiphenyl derivative (top-half segment, 2) in onestep reaction.Both segments were synthesized starting from 2-amino-5methylphenol (4).Carbazole alkaloids are known to show wide range of biological activities such as antitumor, antibiotic, psychotropic, antiinflammatory, and antihistaminic activities. 1 Development of efficient methods for the construction of a carbazole ring is still an important issue. 2While many monomeric carbazoles have been isolated from higher plants, 1 recently, much attention has been focused on biarylic biscarbazole alkaloids 3,4 due to their interesting structures and expected biological activities.N H OMe Me N OMe Me Br Br OMe Me N OMe Me H 2 N SEM OH NH 2 Me murrastifoline-A (1) 1 2 3 9 1' 3' 6' top-half segment (2) bottom-half segment (3) 2-amino-5-methylphenol (4) The Double N-Arylation + (one-step construction of a carbazole ring) Figure.Structure of murrastifoline-A (1) and retrosynthetic way to 1.