Synthesis of (-)-Δ9-tetrahydrocannabinol and (-)-Δ9-tetrahydrocannabivarin metabolites and their regiospecifically deuterated analogs

MEDI 31

Spyros P. Nikas, spyridonnikas@yahoo.com1, Ganesh A. Thakur, gathakur@gmail.com1, Damon Parish2, Shakiru O. Alapafuja, Alapafuja@yahoo.com1, Marilyn A Huestis3, and Alexandros Makriyannis, a.makriyannis@neu.edu1. (1) Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, 116 Mugar Life Sciences Building, 360 Huntington Avenue, Boston, MA 02115, (2) Naval Research Laboratory, Code 6030-4555, Overlook Ave, Washington, DC 20375, (3) Chemistry and Drug Metabolism Section, CPTR Branch, Intramural Research Program, NIDA, NIH, 5550 Nathan Shock Drive, Baltimore, MD
For centuries marijuana has been a popular recreational drug of abuse because of its psychoactive properties. (-)-Δ9-Tetrahydrocannabinol [(-)-Δ9-THC], the major ingredient of marijuana, quickly metabolizes to several cannabinoids-mainly 11-hydroxy-Δ9-THC, 11-nor-9-carboxy-Δ9-THC, and 8β, 11-dihydroxy-Δ9-THC and their glucuronide conjugates. The availability of tetrahydrocannabinols and their metabolites in both their undeuterated and deuterated forms is critical for the analysis of biological and toxicological samples. A recent study tracing the metabolism of marijuana constituents including (-)-Δ9-THC and (-)-Δ9-tetrahydrocannabivarin [(-)-Δ9-THCV] in humans required the synthesis of deuterated analogs as well as their corresponding in vivo metabolites in high isotopic and optical purities. We describe here a concise methodology for the syntheses of (-)-Δ9-THC and (-)-Δ9-THCV metabolites. The synthetic sequence involves a minimum number of steps, avoids undesirable oxidative conditions, and incorporates the costly deuterated fragments near the end of the synthetic sequence.

Acknowledgements:This work was supported by grants from the National Institute on Drug Abuse (DA03801, DA07215 and DA09158)

 

Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Sci-Mix

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007