Stereoselective β-mannosylation via anomeric O-alkylation: Formal synthesis of potent calcium signal modulator acremomannolipin A

Abstract

Stereoselective β-mannosylation has been investigated via cesium carbonate-mediated anomeric O-alkylation of D-mannose-derived lactol with various electrophiles. It was found that electrophiles bearing trifluoromethanesulfonate (triflate) as the leaving group are most reactive. In addition, a highly efficient formal synthesis of potent calcium signal modulator acremomannolipin A has been achieved using this β-mannosylation method.

β‐Mannosylation through O‐Alkylation of Anomeric Cesium Alkoxides: Mechanistic Studies and Synthesis of the Hexasaccharide Core of Complex Fucosylated N‐Linked Glycans

“…Previously, anomeric O ‐alkylation of 3,4,6‐tri‐ O ‐benzyl‐ d ‐mannose 7 with allyl bromide in the presence of Cs 2 CO 3 was found to afford allyl 3,4,6‐tri‐ O ‐benzyl‐ β ‐ d ‐mannoside 43 in 94 % yield ( β only) . Based on that, we conducted reaction progress kinetic analysis involving two different initial concentrations of mannose 7 , in order to establish whether monomeric cesium alkoxide 42 β or its dimeric form is the key reactive intermediate for this anomeric O ‐alkylation (Figure ) .…”

“…of allyl bromide was added to this supernatant containing cesium alkoxide 42 in CDCl 3 and the resulting mixture was stirred at 40 °C for 24 hours to afford desired allyl 3,4,6‐tri‐ O ‐benzyl‐ β ‐ d ‐mannoside (cf. 43 , Scheme ) in 23 % yield. This result indicated that cesium alkoxide 42 β is the reactive species in the anomeric O ‐alkylation.…”

“…It is worth noting that this mild and easily operable β ‐mannosylation method directly affords the desired β ‐mannosides with a free C2‐OH at the mannose residue. The free C2‐alcohol can be directly subjected to subsequent chemical transformations as demonstrated in a formal synthesis of the potent calcium signal modulator acremomannolipin A and a concise synthesis of a trisaccharide oligomer of the Hyriopsis schlegelii glycosphingolipid, respectively …”