Harry G. Pars

Water-Soluble Derivatives of Δ1 Tetrahydrocannabinol

Δ1-Tetrahydrocannabinol, which is resinous and insoluble in water and therefore difficult to study pharmacologically, can be converted to a watersoluble derivative without loss of its biological activity. This has been achieved by preparing esters bearing a nitrogen moiety with the use of carbodiimide as the condensing agent. The availability of such water-soluble derivatives will allow the evaluation of Δ1-tetrahydrocannabinol in self-administration studies in monkeys for its addiction liability potential in man. This technique of water solubilization is also applicable to other compounds of chemical and biological significance.

TETRAHYDROCANNABINOLS AND SYNTHETIC ANALOGS

Classical studies of the resinous cannabinoid fraction of the plant by Adams,’ Todd,2 and Cahn3 and more recently by T a y l ~ r , ~ M e c h o ~ l a m , ~ and their COworkers led to the definitive structural assignments shown in I and 11. During the study of the natural tetrahydrocannabinols in the 1940s, Adams and his collaborators prepared totally synthetic tetrahydrocannabinols 111, not found in the plant, which differed from the naturally derived THC’s in the relative position of the double bond in the alicyclic ring:

Water-soluble derivatives of 1 -tetrahydrocannabinol.

Δ1-Tetrahydrocannabinol, which is resinous and insoluble in water and therefore difficult to study pharmacologically, can be converted to a watersoluble derivative without loss of its biological activity. This has been achieved by preparing esters bearing a nitrogen moiety with the use of carbodiimide as the condensing agent. The availability of such water-soluble derivatives will allow the evaluation of Δ1-tetrahydrocannabinol in self-administration studies in monkeys for its addiction liability potential in man. This technique of water solubilization is also applicable to other compounds of chemical and biological significance.

Heterocyclic Analogs of the Cannabinoids

This paper presents chemical and pharmacological data on a series of nitrogen- and sulfur-containing benzopyrans structurally and historically related to the cannabinoids. These new classes of compounds are benzopyranopyridines, thiopyranobenzopyrans, thienobenzopyrans, and their water-soluble ester derivatives. Representatives of these agents are currently under investigation in animals and man to determine their therapeutic potential.

Water-Soluble Derivatives of Dgr1 Tetrahydrocannabinol

Δ1-Tetrahydrocannabinol, which is resinous and insoluble in water and therefore difficult to study pharmacologically, can be converted to a watersoluble derivative without loss of its biological activity. This has been achieved by preparing esters bearing a nitrogen moiety with the use of carbodiimide as the condensing agent. The availability of such water-soluble derivatives will allow the evaluation of Δ1-tetrahydrocannabinol in self-administration studies in monkeys for its addiction liability potential in man. This technique of water solubilization is also applicable to other compounds of chemical and biological significance.

Lithium-ammonia reduction of tetrahydrocannabinols

Bei der Reduktion mit Lithium/Ammoniak erhalt man aus dem Chromen (I) unter Ringspaltung das Phenol (II).