Total synthesis of phomazarin

A concise total synthesis of phomazarin (1) is detailed enlisting a heteroc yclic azadiene inverse electron demand Diels-Alder reaction (1,2,4-triazine --> pyridine) for preparation of the fully substituted and appropriately f unctionalized pyridine C-ring. Thus, [4 + 2] cycloaddition (85%) of triethy l 1,2,4-triazine-3,5,6-tricarboxylate (2) with trimethoxyethylene (3) follo wed by conversion of the cycloadduct 11 to the cyclic anhydride 13 provided the phomazarin C-ring with the three carboxylates suitably differentiated. Linkage of the A- and C-rings through selective nucleophilic addition of t he aryllithium reagent 9 to the least hindered anhydride carbonyl of 13 fol lowed by Friedel-Crafts closure of the B-ring provided the fully functional ized phomazarin skeleton. The successful structural correlation of syntheti c 1 with natural material and its derivatives confirmed the latest structur al assignment for the natural product.