Optimization of a Kilogram-Scale Synthesis of a Potent Cycloartenol Triterpenoid-Derived γ-Secretase Modulator

This work describes the demonstration of a kilogram-scale synthesis of a γ-secretase modulator from a plant-sterol-derived starting material. Key to developing a synthetic route capable of delivering a kilogram of the target compound was the development of a four-reaction telescope process and a selective O-alkylation of a triol intermediate. These improvements enabled the successful delivery of kilogram-scale batches of API for preclinical development studies.