The plant, Mitragyna speciosa (or kratom), has a long history of use in many regions of South-East Asia for treatment of various ailments. In the last decade, kratom has gained significant interest and the usage of the dry leaf material has escalated in U.S. along with the number of anecdotal reports that point to the efficacy of kratom in a range of disorders with limited therapeutic options, including opioid dependence, treatment-resistant depression, anxiety, and pain syndromes. A number of alkaloids in this plant, including mitragynine (MG) and its oxidation product 7-hydroxymitragynine (7OH), have been found to bind to opioid receptors (is a partial mu-opioid receptor (MOR) agonist) and represent novel molecular scaffolds for the development of opioid receptor modulators with a much-improved side effect profile as compared to morphine and other MOR agonists.
We focus on devising new synthetic methods to gain access to derivatives of MG and 7OH which will help in examining and studying specific unexplored positions in structure-activity relationship (SAR) studies. Along with the synthesis of the novel analogs we describe the pharmacological and behavioral studies of a subset of its novel analogs which can potentially lead to a development of safer opioid therapeutics.