Pyrrole-2-carboxaldehyde → 1-(beta-D-Ribofuranosyl)pyrrole-2-carbaldehyde

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Reaction Steps

To a solution of pyrrole-2-carbaldehyde (330 mg, 3.5 mmol) in CH3CN (18 ml), NaH (60% oil dispersion, 152 mg, 3.8 mmol) was added and stirred at room temperature for 45 minutes, followed by addition of a solution of 2,3,5-tri-O-benzyl-D-ribofuranosyl chloride (3.1 mmol) (Non-patent Document 44) in CH3CN (18 ml). The reaction mixture was stirred at room temperature for 4 hours. The product was partitioned between ethyl acetate and water, and the organic layer was washed three times with saturated aqueous sodium chloride, dried over Na2SO4, and then evaporated under reduced pressure to remove the solvent. The residue was purified by silica gel chromatography (eluted with 20% ethyl acetate in hexane) to give crude 1-(2,3,5-tri-O-benzyl-D-ribofuranosyl)pyrrole-2-carboxyaldehyde (506 mg). After the crude 1-(2,3,5-tri-O-benzyl-D-ribofuranosyl)pyrrole-2-carboxyaldehyde (506 mg, 1.0 mmol) was azeotroped with toluene, CH2Cl2 (17 ml) was added to the residue. To this solution, BBr3 (1 M solution, 3.0 ml) was added at −78° C. and stirred for 2.5 hours, followed by addition of a 50% methanol-CH2Cl2 solution (25 ml). After the solution was stirred at −78° C. for 10 minutes, 28% NH4OH (0.5 ml) was added. The reaction mixture was further stirred until it reached room temperature. The product was partitioned between CH2Cl2 and H2O, and the aqueous layer was washed three times with CH2Cl2 and evaporated under reduced pressure to remove the solvent. The product was purified by reversed-phase C18 HPLC to give 1-(β-D-ribofuranosyl)pyrrole-2-carbaldehyde (108 mg, 15%, 2 steps).

Provenance & Evidence