Synthese der L-glycero-D-manno-heptose

Stereoselective Glycal Fluorophosphorylation: Synthesis of ADP‐2‐fluoroheptose, an Inhibitor of the LPS Biosynthesis

“…[15] In contrast, the synthesis of glucosylheptoses has been much less investigated. [16,17] Thus, we first explored the stereoselective preparation of l-glycero-d-glucoheptoses from a key olefin intermediate 4 derived from dglucose.…”

“…Selectfluor-(TfO) 2 (761 mg, 1.59 mmol) was added very quickly at 0 8C, and the reaction mixture was allowed to warm to room temperature. After 12 h of stirring, sodium dibenzylphosphate (955 mg, 3.18 mmol) and [15]crown-5 (700 mg, 3.18 mmol) was added with flowing argon gas, and the mixture was heated to 60 8C and stirred for 16 h. The suspension was filtered through a pad of Celite, and the pad was washed with dichloromethane. The filtrate was concentrated in vacuo, and the residue was subjected to chromatography on silica gel (hexane/ethyl acetate 5:1) to give fluorophosphate 14 (497 mg, 58 %) as a colorless syrup.…”

“…Selectfluor (1.8 g, 3.70 mmol) was added at 0 8C and the reaction mixture was stirred for 20 h at ambient temperature. [15]Crown-5 (1.5 mL, 7.50 mmol) and dibenzylphosphate (sodium salt, 2.25 g, 7.50 mmol) were then added and the resulting solution was warmed to 45 8C for 36 h. The mixture was diluted with EtOAc (200 mL), filtered, and concentrated under low pressure. The residue was finally purified by flash chromatography (hexane/ EtOAc [38] (600 mg, 1.23 mmol) was solubilized in nitromethane (24 mL) and stirred with 4 molecular sieves (1 g) under argon for 15 min.…”

“…Selectfluor (500 mg, 1.04 mmol) was added at 0 8C and the reaction mixture was stirred for 4 h at ambient temperature. [15]Crown-5 (736 mL, 3.68 mmol) and dibenzylphosphate (sodium salt, 1.0 g, 3.33 mmol) were then added and warmed to 45 8C for 48 h. The mixture was diluted with EtOAc (100 mL), filtered, and concentrated under low pressure. The residue was finally purified by flash chromatography (hexane/EtOAc, 5.…”

“…Therefore, we employed the sodium salt of dibenzyl phosphate in presence of [15]crown-5 ether (15C5) and decreased the temperature of the reaction. With this new procedure (entry 6), we could observe that, starting from the same glucal 16, the yield and the stereoselectivity were both improved at 60 8C.…”