Scalable Synthesis Routes to Cannabinoids

Abstract

(-)-Cannabidiol ((-)-CBD) is the main phytocannabinoid isolated from Cannabis sativa; recently (-)-cannabidiol based medicines have been regulated by the Medicines and Healthcare products Regulatory Authority for the treatment of Lennox Gastaut and Dravet syndrome, which are forms of childhood epilepsy. (-)-CBD has garnered significant interest from the pharmaceutical and nutraceutical industries due to both its non-psychoactive nature and its promising therapeutic profile for use in the treatment of a variety of diseases. However, the limited availability and high costs associated with the extraction and purification of (-)-CBD from natural sources has catalysed research into the development of new synthetic methods to access (-)-CBD and its analogues.

This thesis begins with a comprehensive review of the current state of the art pertaining to (-)-CBD synthesis, exploring the current limitations and challenges. Subsequently, an in-depth study and route development based upon key identified precursor molecules was conducted. The investigation encompasses the design and synthesis of methyl olivetolate and p-menthadienol, as well as their assembly into the final chemical structure, cannabidiol (-)-CBD. The primary overarching objective of the thesis is the development of a scalable and cost-effective processing solution to these precursors and (-)-CBD which can be translated to the sponsoring industrial partner Sterling Pharmaceutical Solutions for manufacture.