Masked Thiol Sugars: Chemical Behavior and Synthetic Applications of S‐Glycopyranosyl‐N‐monoalkyl Dithiocarbamates

Abstract

The chemical behavior of S-glycopyranosyl-N-monoalkyl dithiocarbamates (DTCs) as masked 1-glycosyl thiols, easily prepared by the nucleophilic displacement of 1-halo sugars with dithiocarbamate salts of primary amines, has been studied and synthetically exploited. This behavior relies on the abstraction of the proton of the carbamate functionality that allows controlled access to thiolate sugar intermediates. The basic character of the DTC salts used as reagents leads to thiolates that evolve in situ to symmetrical diglycosyldisulfides (DGDSs) when long reaction times are allowed. Alternatively, controlled unmasking of the thiolate function can be efficiently attained by treatment with an external base of isolated anomeric glycosyl DTCs, the formation of which is prevalent when using short reaction times. In this manner, a second methodology for the preparation of symmetrical DGDSs and a chemical protocol for the S-glycosylation of any electrophilic substrate are established. The applications of this last strategy for the preparation of thioglycosyl vinyl sulfones, thiodisaccharides, and S-linked homo- and heterodivalent neoglycoconjugates are described as a proof-of-concept of the great potential of the sugar DTCs in any chemical scenario in which the covalent attachment of a thiol sugar is required. The evaluation of the biological functionality of some divalent sulfurated sugar systems is also described.

Total Synthesis of Calanthoside, a Potential Hair Growth Stimulant: A Facile Synthetic Approach via One-Pot S- and O-Glucosidic Bond Formation

“…We made another attempt to glucosylate 8 with 7a using K 3 PO 4 as an alternative base to K 2 CO 3 . O -Glycosylation products 6a and 19a were detected in the crude mixture; however, the disulfide 20 was unexpectedly formed. Additionally, the polarity among the starting material 8 and products 6a , 19a , and disulfide 20 were close, thus complicating reaction monitoring (entry 4).…”

“…The extract was washed with brine (10 mL) and concentrated in vacuo. The residue was purified by column chromatography ( n -hexane/EtOAc = 3:1) to give a pale brown amorphous residue (211 mg) including N -acetyl-3-(2,3,4,6-tetra- O -acetyl-β- d -glucopyranosyloxy)-1 H -indol-2-yl 2,3,4,6-tetra- O -acetyl-1-thio-β- d -glucopyranoside ( 6a , 62 mg, 71 μmol, 19%), 3-(2,3,4,6-tetra- O -acetyl-β- d -glucopyranosyloxy)-1 H -indol-2-yl 2,3,4,6-tetra- O -acetyl-1-thio-β- d -glucopyranoside ( 19a , 83.0 mg, 101 μmol, 27%), and bis­(2,3,4,6-tetra- O -acetyl-β- d -glucopyranosyl) disulfide ( 20 , 66 mg, 91 μmol, 25%). Yields of 6a , 19a , and 20 were estimated from the 1 H NMR spectrum (600 MHz) of the mixture.…”

Synthesis of Thiodisaccharides Bearing N‐Acetylhexosamine Residues: Challenges, Achievements and Perspectives

“…Besides, in 2014, Megia-Fernandez et al [90] reported the ring-opening reaction of a cyclic sulphate mediated by a thioaldose, as a key reaction for the synthesis of thiodisaccharides. Like cyclic sulphamidates, cyclic sulphates proved to be versatile synthons as epoxide equivalents in organic synthesis.…”

“…Besides, in 2014, Megia‐Fernandez et al [90] . reported the ring‐opening reaction of a cyclic sulphate mediated by a thioaldose, as a key reaction for the synthesis of thiodisaccharides.…”