Process Development of Purpurin 18: Paving the Way for Kilogram-Scale Manufacturing of Chlorophyll <i>a</i> Derivatives

A safe, robust, and scalable process for synthesizing purpurin 18 (PP18) has been developed. Conventional methods for producing PP18 from chlorophyll a or its derivatives have faced challenges in yield and operability, with no reports of large-scale production. Spirulina powder, which is readily available and cost-effective, was selected for isolating and purifying chlorophyll a. A precipitation method established by Watanabe et al. was refined to achieve a simple procedure yielding high recovery and excellent purity. Reaction conditions for converting chlorophyll a into PP18 were then optimized based on Q-TOF-MS (quadrupole time-of-flight mass spectrometry) analysis. A two-step oxidation mechanism via a keto-carboxylic acid intermediate was clarified, leading to substantial improvements in reaction conditions and yields. This process was successfully scaled up using 1200 kg of Spirulina powder, providing 10.5 kg of chlorophyll a and subsequently 3.9 kg of PP18. This appears to be the first report of the kilogram-scale manufacturing of PP18, providing important insights for diverse fields that utilize chlorophyll a derivatives.