Asymmetric formal synthesis of azadirachtin

An asymmetric formal synthesis of azadirachtin, a potent insect antifeedant, was accomplished in 30 steps to Ley's synthetic intermediate (longest linear sequence). The synthesis features: 1) rapid access to the optically active right-hand segment starting from the known 5-hydroxymethyl-2-cyclopentenone scaffold; 2) construction of the B and E rings by a key intramolecular tandem radical cyclization; 3) formation of the hemiacetal moiety in the C ring through the α-oxidation of the six-membered lactone followed by methanolysis. The asymmetric formal synthesis of azadirachtin (1) was accomplished by utilizing the tandem radical cyclization reaction as a key step. The route to the key intermediate 2 requires the longest linear sequence of 30 steps.