Rapid separation of L-gossypol using chiral derivatizing reagent combined with ultrasonic crystallizatio

Gossypol, a natural polyphenolic compound, has notable medicinal and economic value due to its strong antitumor activity.Its primary active form, levorotatory gossypol (L-gossypol), exhibits optical activity.However, the existing methods for separating L-gossypol face challenges such as complexity, low yield, and high costs.Traditional techniques like column chromatography are unsuitable for industrial-scale production.While the crystallization separation could achieve gram-scale yields with relatively lower overall costs, ensuring purity required several days for one production cycle.In this study, we innovatively employed a combination of a chiral derivatizing reagent (CDR) and ultrasonic crystallization to achieve a rapid and cost-effective separation of L-gossypol.Ultrasonic crystallization uses ultrasound-induced cavitation to drive crystallization.The method involves the use of an economical chiral resolving agent, specifically (S)-1-(p-nitrophenyl)-1,3-dihydroxypropanamine, which reacts with racemic gossypol to produce derivatives with distinct physical properties.Ultrasonic crystallization in ethyl acetate serves to efficiently crystallize L-gossypol derivatives.Acid hydrolysis is then employed to remove the chiral resolving agent, resulting in high-purity L-gossypol products.Notably, this streamlined process reduces the separation duration from 4 days, as reported in existing literature, to a single day.Establishing a cyclic process enables continuous production of substantial amounts of high-purity L-gossypol.Within 24 h, crystal yield reached 43.80% with 97.89% optical purity; after hydrolysis, the total yield was 40.45% with 97.07%optical purity.Furthermore, the separated L-gossypol samples exhibit significant antitumor activity.The developed approach offers a promising application prospect for enhancing the efficiency and scalability of L-gossypol production in industrial settings.