Synthesis And Evaluation Of Simplified Analogs Of Laurenditerpenol For Cannabinoid And Anticancer Potentials

The cannabinoid receptors (CB1 and CB2) comprise part of the endocannabinoid system (ECS) and have been implicated in many human diseases such as obesity, anorexia, chronic pain, and cancer [1]. There are many psychotropic drawbacks to targeting CB1 receptors which are primarily found in the central nervous system. Specifically targeting CB2 receptors, which are primarily located on immune cells and probably responsible for the immunosuppressive and antinociceptive effects of cannabinoids, is emerging as a key strategy for the pharmaceutical development of this class of compounds [2]. Laurenditerpenol (LDT), which is a marine bicyclic diterpene isolated from red algae Laurencia intricata, was found to control the expression of genes that influence cell survival and tumor angiogenesis required for cancer tumor growth through hypoxia-inducible factor 1 (HIF-1) inhibition. LDT is a complex molecule containing an unprecedented 7-oxabicyclo [2.2.1] heptane ring system and continuous nonfunctional stereogenic centers [3]. In the present work, using Prins cyclization, we synthesized many simplified analogs of LDT to determine if simplified analogs may possess CB2/anticancer properties. The synthetic details, biological activities of these analogs against the CB1 and/or CB2 receptors as well as the anticancer potential of these analogs will be discussed.

Fig. 1

Acknowledgements: This research is supported in part by The United States Department of Agriculture, Agricultural Research Service, Specific Cooperative Agreement No. 58 – 6408 – 1-603 – 07.

References: [1] Yrjola S, et al. (2015) Euro. J. Pharmaceutical Sci., 67: 85 – 96. [2] Patil KR, et al. (2015) Curr. Med. Chem., 22:3472 – 3501. [3] Chittiboyina, A.G., et al. (2013), J. Org. Chem., 78, 9223 – 9232.