Cannabinol: History, Syntheses, and Biological Profile of the Greatest "Minor" Cannabinoid.

Cannabis ( Cannabis sativa L.) is an outstanding source of bioactive natural products, with more than 150 different phytocannabinoids isolated throughout the decades; however, studies of their bioactivity have historically concentrated on the so-called "big four" [∆ 9 -THC ( 1a ), CBD ( 2a ), CBG ( 3a ) and CBC ( 4a )]. Among the remaining products, which have traditionally been referred to as "minor cannabinoids", cannabinol (CBN, 5a ) stands out for its important repercussions and implications on the global scientific landscape. Throughout this review, we will describe why CBN ( 5a ) deserves a prominent place within the so-called "cannabinome", providing an overview on its history, the syntheses developed, and its bioactivity, highlighting its promising pharmacological potential and the significant impact that the study of its chemistry had on the development of new synthetic methodologies.