Total Synthesis and Absolute Configuration of Macrocidin A, a Cyclophane Tetramic Acid Natural Product

摘要

Macrocidin A (1) and macrocidin B (2) represent a new family of plant pathogens produced by Phoma macrostoma, a microorganism parasitic to Canadian thistle. The intriguing structure of 1, which includes a tetramic acid group installed in a cyclophane skeleton, was determined by extensive 2D NMR studies and single-crystal X-ray analysis, although the absolute configuration remains to be addressed because of a paucity of the natural sample. The macrocidins have significant herbicidal activity on broadleaf weeds but not on grasses, which makes them a potential lead for new herbicide design. Their biological activity and novel chemical structures have made these compounds attractive targets for chemical synthesis. Whilst construction of the macrocyclic skeleton has been addressed, the synthesis of the full structure remains to be achieved. Herein, we describe the first total synthesis of macrocidin A (1) using macrolactam formation followed by cyclization.