ГЕТЕРОЦИКЛИЧЕСКИЕ ТИОПРОИЗВОДНЫЕ КАМФЕНА С ФРАГМЕНТОМ ФЕНИЛТЕТРАЗОЛА

Abstract

It is known that the tetrazole ring is an important pharmacophore fragment included in the structure of drugs with more than 20 types of biological activity. In order to obtain new biologically active thioterpenoids with heterocyclic fragments, we set the task of combining the natural terpene skeleton and the nitrogen-containing heterocyclic function through the biogenic sulfur atom. We have used thiylation and sulfenylchlorination of (+)-camphene and its derivatives, which are difficult to obtain synthetically (cyclopropene and allene), with 1-phenyltetrazole-5-thiol and 1-phenyltetrazole-5-sulfenyl chloride. Studying the structure of hetarene sulfide obtained by the reaction of camphene with 1-phenyltetrazole-5-thiol in the presence of a Lewis acid (boron trifluoride etherate), allowed us to conclude that during the reaction a Wagner-Meerwein rearrangement occurs. The rearrangement leads to isomerization of the initial camphane structure with the formation of a terpene sulfide of bornane structure with an exo-position of the sulfide group relative to the bicyclic skeleton of the molecule. In non-catalytic sulfenylchlorination reactions isomerization of the camphene skeleton is not observed. 2,2-Dimethylnorbornane-3-spirocyclopropene forms the product of the “normal” addition of 1-phenyltetrazole-5-sulphenyl chloride to the double bond of cyclopropene. A mixture of two regioisomers with a trans-position of the sulfide group and a chlorine atom is observed. In this case, the chlorine atom is located on the endo side of the cyclopropane ring relative to the gem-dimethyl group, while the sulfide group is on the exo side. Sulfenylchlorination of 2,2-dimethyl-3-ethenylidenenorbornane occurs regio- and stereospecifically at a sterically less hindered double bond, with the sulfide group located at the C-10 atom and the chlorine atom at the C-11 atom.