Synthetic Strategies for (−)‐Cannabidiol and Its Structural Analogs

Abstract

À)-Cannabidiol ((À)-CBD), an on-psychoactive phytocannabinoid from Cannabis,a nd its structural analogs have received growinga ttention in recent years because of their potentialt herapeutic benefits, including neuroprotective, anti-epileptic,a nti-inflammatory,a nxiolytic, and anticancer properties. (À)-CBD and its analogs have been obtained mainly based on extraction from the natural source; however,t he conventional extraction-based methods have some drawbacks, such as poor quality controla long with purification difficulty.C hemical-synthetic strategies for (À)-CBD could tackle these issues, and, additionally,g enerate novel (À)-CBD analogs that exhibit advanced biological activities. This review concisely summarizes the historic and recent milestones in the synthetic strategies for (À)-CBD and its analogs.

Cannabidiol Discovery and Synthesis—a Target‐Oriented Analysis in Drug Production Processes

“…[103] Despite several studies describing the isolation and purification of CBD from plant material, [22,23] policies that prohibit growing Cannabis plants also limit access to these derivatives, which are not otherwise regulated. [104,105] Thus, chemical synthesis becomes an important alternative to obtain active compounds.I nterest in cannabinoid-based drugs has motivated the developmento fn ew synthetic routes for (À)-2 [25] and its analogues. [106][107][108][109]…”

“…Thus, chemical synthesis becomes an important alternative to obtain active compounds. Interest in cannabinoid‐based drugs has motivated the development of new synthetic routes for (−)‐ 2 [25] and its analogues [106–109] …”

“…[24] In this scenario, the implementation of as calablea nd competitive synthetic process, suitable for pharmaceutical quality standards, is desirable. Recent literature reviews addressed the synthesis of CBD and other cannabinoids; [5,[25][26][27][28][29] however,t hese studies have paid less attentiont oc hallenges and alternative approaches.…”

Synthetic pathways to tetrahydrocannabinol (THC): an overview

“…4,5 Although a large collection of synthetically prepared cannabinoids have been reported, the synthetic approaches employed have not yet been systematically reviewed for tetrahydrocannabinol. 15 Here we will provide an overview of the most prominent synthetic pathways to the THC scaffold. This is of interest from both a medicinal chemistry viewpoint, as it will shed light on possible new cannabinoid derivatives to be synthesised, but also from a synthetic organic chemistry angle, as the synthesis of the terpenoid C-ring of THCs is especially challenging requiring creative synthetic solutions ( Fig.…”

A review on the syntheses of Dronabinol and Epidiolex as classical cannabinoids with various biological activities including those against SARS-COV2

“…In 2004, the use of a Cannabis sativa L. (Marijuana) extract was confirmed as a safe and effective treatment for HIV/AIDS, arising from anorexia and chemotherapy, from nausea and vomiting, multiple sclerosis through the United States Food and Drug Administration (USFDA) [22,23]. The active ingredient of this approval medicine, Dronabinol (trade names Marinol and Syndros) is a purified Cannabisderived (−)-Δ 9 -trans-tetrahydrocannabinol [24,25].…”