Compound 17

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Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

To a 50 mL, single-necked, oven-dried, pear-shaped flask was added 10 mL of CH₂Cl₂ which was cooled to –78 °C and stirred for 10 min before adding (COCl)₂ (596 μL, 6.95 mmol, 5.00 equiv). The solution was then stirred for another 10 min before adding DMSO as a solution in anhydrous CH₂Cl₂ (2.80 M, 5.00 mL, 13.9 mmol, 10.0 equiv) slowly dropwise via plastic syringe. The resulting solution was stirred for 40 min at –78 °C. Then diol (–)-16 was added as a solution in CH₂Cl₂ (0.15 M, 220 mg, 1.39 mmol, 1.00 equiv) slowly dropwise via plastic syringe and stirred for 1 h. Et₃N (3.87 mL, 27.8 mmol, 20.0 equiv) was then added to the reaction mixture quickly along the wall of the flask via plastic syringe. The reaction mixture was then stirred for 30 min at –78 °C before replacing cooling bath with a 0 ºC ice bath and stirring for 1 h. The reaction mixture was quenched with saturated, aqueous NaHCO₃, extracted with CH₂Cl₂ (3 x 15 mL), dried over MgSO₄, filtered through Celite, and concentrated by rotary evaporation to give a crude oil which was used in the next step without purification. To a 50 mL, single-necked, pear-shaped flask charged with crude material was added 7.00 mL of AcOH and 7.00 mL of Ac₂O, followed by NaOAc (1.14 g, 13.9 mmol, 10.0 equiv) and concentrated H₂SO₄ (74.0 μL, 1.39 mmol, 1.00 equiv). The reaction mixture was stirred at ambient temperature (23 ºC) for 48 h, poured into saturated aqueous NaHCO₃ solution (50 mL), and the aqueous layer was extracted with EtOAc (3 x 50 mL). The combined organic layer was washed with brine (20 mL), dried over MgSO₄, filtered through Celite, and concentrated under reduced pressure to give a crude oil which was filtered through a short column of silica gel to afford bis-acetoxy furanose 17 as a mixture of four diastereomers which was used in the following step without further purification: TLC, R_f = 0.39 (EtOAc/hexanes, 1:1 v/v). This bis-acetoxy furanose displayed some instability issues so was carried on directly to the following reduction/dehydration sequence without further characterization.