Synthesis of Novel Propynyl Monoterpene Analogues and their Conjugates with β-DGlucopyranosides

Abstract

: Camphor and carvone exhibit a broad spectrum of biological activity, which determines the prospect of their use as a platform for functionalization to obtain the analogues as potential drugs. The functionalization of camphor and carvone often involves changes to the skeleton of the molecules or their fragmentation. Therefore, in modern medicinal chemistry, research aimed at the development of effective approaches to the synthesis of semi-synthetic derivatives of camphor and carvone with preservation of the native framework, demonstrating high biological activity, is in demand. The present work is aimed at the synthesis of new propynyl analogues of camphor and carvone, as well as their conjugates with mono- and disaccharides via Cu-catalyzed cycloaddition of acetylenes and azides (CuAAC). Alkylation of camphor and carvone with propargyl bromide in the presence of the base KN(SiMe3)2–Et3B in 1,2-dimethoxyethane (DME) at room temperature provides the target products with yields of 69% and 47%, respectively. Glycosyl azides were obtained by the reaction of peracetylated sugars with trimethylsilyl azide in the presence of SnCl4.The synthesis of 1,2,3-triazolyl glycoconjugates of camphor and carvone with mono- and disaccharides was carried out through Cu(I)-catalyzed 1,3-dipolar cycloaddition of azides to acetylenes (CuAAC) in the presence of Cu and CuSO4·5H2O. The structures of the synthesized compounds were determined by NMR. The new propynyl-substituted camphor and carvone, as well as their 1,2,3-triazolylglycoconjugates, can be used as promising building blocks for medicine chemistry.