Synthesis of alkyl and cycloalkyl α-d-mannopyranosides and derivatives thereof and their evaluation in the mycobacterial mannosyltransferase assay

Antitubercular Drugs Based on Carbohydrate Derivatives

“…It was previously demonstrated that the C-6 deoxy D-mannose analog hinders α-(1,6)-ManT activity, suggesting that mannose transfer takes place at the C-6 position of the acceptor substrate [195]. To confirm this finding, a triazole-linked 1,6-dimannoside acceptor substrate (Fig.…”

“…Compounds 18.12.3 and 18.12.4 were synthesized and tested for ManT acceptor activity and compared against compound 18.12.5, known for its ManT acceptor activity, and has the minimum structural requirements as synthetic acceptor (Fig. 18.12.5) [195,196]. These octyl glycosides act as substrate analogs for GTs in the mycobacteria [121,[197][198][199].…”

Synthesis of modified D-mannose core derivatives and their impact on GH38 α-mannosidases

“…The residue was purified by column chromatography (hexane:EtOAc 4:1→2:1) providing 9 (0.20 g, 93%) as a colourless oil. 1 (10) 22 .…”

“…13,14 The model compounds failed to inhibit ManT, instead, they served as good acceptor substrates. [10][11][12] They were more potent inhibitors of GH47 than GH38 α-mannosidases. 13,14 One of the GH38 enzymes, human Golgi α-mannosidase II (hGMII) (EC 3.2.1.114), is a very attractive target.…”

“…In our ongoing research, synthetic mannose derivatives have been constructed as models for mycobacterial mannosyltansferase (ManT) [10][11][12] or eukaryotic α-mannosidases belonging to glycoside hydrolase families 38 and 47. 13,14 The model compounds failed to inhibit ManT, instead, they served as good acceptor substrates.…”