Synthesis of ursane-derived isothiocyanates and study of their reactions with series of amines and ammonia

Abstract

ABSTRACT Based on ursolic acid, 3 compounds with isothiocyanate groups located at different distances from C-17 of the triterpenoid core have been synthesized through ursane-derived primary amines. To obtain terpene hybrids with thioureas and N,S-containing heterocycles, series of amines and ammonia were reacted with novel isothiocyanates. In the reactions with propargylamine, 3 triterpenoid hybrids with 4,5-dihydrothiazol-2-yl-amine have been selectively obtained in 81%–91% yields. Isothiocyanates containing several bonds between the -CNS group and the triterpenoid backbone reacted with (1-aryl-1H-1,2,3-triazole-4-yl)methanamines, as well as with ammonia, to form thiourea derivatives (78%–94%). The nor-compound with a -CNS group at C-17 of the triterpenoid was the least reactive due to deactivation by a donor terpene branched substituent and reacted readily only with sufficiently strong nucleophiles, such as primary and secondary aliphatic amines. The reaction of the nor-derivative of isothiocyanate 7 with ammonia at elevated temperature led to the unexpected formation of 3β-acetoxy-28-norurs-12-en-17-yl-amine, the precursor of isothiocyanate, as the main product (82%).