Amine-linked diglycosides: Synthesis facilitated by the enhanced reactivity of allylic electrophiles, and glycosidase inhibition assays

Abstract

SummaryDiglycose derivatives, consisting of two monosaccharides linked at non-anomeric positions by a bridging nitrogen atom, have been synthesised. Conversion of one of the precursor monosaccharide coupling components into an unsaturated derivative enhances its electrophilicity at the allylic position, facilitating coupling reactions. Mitsunobu coupling between nosylamides and 2,3-unsaturated-4-alcohols gave the 4-amino-pseudodisaccharides with inversion of configuration as single regio- and diastereoisomers. A palladium-catalysed coupling between an amine and a 2,3-unsaturated 4-trichloroacetimidate gave a 2-amino-pseudodisaccharide as the major product, along with other minor products. Derivatisation of the C=C double bond in pseudodisaccharides allowed the formation of Man(N4–6)Glc and Man(N4–6)Man diglycosides. The amine-linked diglycosides were found to show weak glycosidase inhibitory activity.

Chemical Modification of Polysaccharides

“…The reactions are normally high-yielding and regioselective, so it is often possible to refunctionalise the primary position of an unprotected monosaccharide [96]. However, a limited number of reactions of secondary carbohydrate alcohols are known.…”

Brønsted Acid Catalyzed Monoalkylation of Anilines with Trichloroacetimidates

“…Additionally, allylic trichloro­acetimidates have been used as substrates for transition-metal-catalyzed allylic amination with aniline nucleophiles. These reactions employ catalysts based on rhodium, iridium, or palladium . Fewer studies have evaluated protic acids in these N-substitution reactions, although (PhO) 2 PO 2 H was recently used with aniline and a highly reactive isatin derived trichloro­acetimidate and TsOH was evaluated in the alkylation of anilines with tert -butyl-2,2,2-trichloroacetimidate …”

Modication of Heterocyclic Amino Acids: Histidine and Tryptophan

“…The reactions are normally highyielding and regioselective, so it is often possible to refunctionalise the primary position of an unprotected monosaccharide [96]. However, a limited number of reactions of secondary carbohydrate alcohols are known.…”