Total Synthesis of Ajudazol A by a Modular Oxazole Diversification Strategy

Abstract

The total synthesis of the potent respiratory chain inhibitor ajudazol A was accomplished by a concise strategy in 17 steps (longest linear sequence). The modular approach was based on a direct oxazole functionalization strategy involving a halogen dance reaction for selective halogenation in combination with a challenging combination of sp²-sp² and sp²-sp³ Negishi cross coupling reactions. The applicability of this strategy for analogue synthesis was demonstrated by the synthesis of a simplified as well as stabilized ajudazol analogue.