Efficient and highly stereoselective assembly of rosuvastatin

We report an asymmetric synthesis of rosuvastatin starting from an α,β-unsaturated aldehyde precursor containing the rosuvastatin heterocyclic core at its terminus. The α,β-unsaturated carbonyl starting material was used in a highly stereoselective Ti-catalyzed aldol condensation followed by a syn-selective Narasaka–Prasad borane-ketone reduction and hydrolysis step to provide rosuvastatin calcium. This approach provides concise access to stereochemically pure rosuvastatin from simple and readily available starting materials in 3 steps. The overall three-step process provides rosuvastatin calcium in 80% yield, >99:1 syn/anti ratio, and >99% ee.