Batch and Continuous Flow Total Synthesis of Cannabidiol

Author(s):Show less -

Braga, Felipe C. ; da Silva, Felipe L. N. ; Ramos, Tiago de O. ; Rosa, Joao G. H. ; Araujo, Erica de A. ; Junior, Nelson F. C. ; Wendler, Edison P. ; Beatriz, Adilson ; de Souza, Rodrigo O. M. A. ; Brocksom, Timothy J. ; de Oliveira, Kleber T.

• Document type: Journal article
• Source: CHEMISTRY-AN ASIAN JOURNAL; v. 19, n. 20, p. 7-pg., 2024-10-16.

Abstract

Herein, we present a comprehensive total synthesis of cannabidiol integrating both batch and continuous flow conditions. Our approach is planned to streamline the synthesis of olivetolic acid derivatives and utilize an enantiomerically pure monoterpene moiety obtained from naturally occurring (R)-(+)-limonene by photocatalysis. Key reactions, including the synthesis of olivetolic ester and a Friedel-Crafts alkylation, are successfully adapted to continuous flow, resulting in improved yields and selectivities. This study not only offers a scalable and efficient route for cannabidiol synthesis but also contributes to the synthetic approaches to access cannabinoids (diversity synthesis), with potential applications in medicinal and industrial contexts. We present a batch and continuous-flow synthetic approach to produce Cannabidiol. Our route is based on the total synthesis of Cannabidiol, where the monoterpene portion is derived from biomass (orange peels) and the resorcinol portion is obtained in a two-step synthesis. This study offers a scalable and efficient route for the synthesis of Cannabidiol, providing various benefits compared to extraction from Cannabis sativa, such as greater control of impurities, better quality control, and easier regulation. image (AU)

• FAPESP's process: 13/07276-1 - CEPOF - Optics and Photonic Research Center
• Grantee: Vanderlei Salvador Bagnato
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 20/06874-6 - Applications of technologies and synthetic methodologies developed under continuous flow conditions at LQBO-UFSCar for the preparation of molecules with biological activities and APIs
• Grantee: Kleber Thiago de Oliveira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 23/04020-8 - APIs synthesis using enabling technologies: approaches involving electrosynthesis and photocatalysis under continuous flow conditions
• Grantee: Kleber Thiago de Oliveira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 21/06110-9 - Application of continuous flow chemistry in the synthesis of Active Pharmaceutical Ingredients (APIs): cannabidiol, fentanyl, and ibuprofen
• Grantee: Felipe Camargo Braga
• Support Opportunities: Scholarships in Brazil - Post-Doctoral