Methanesulfonic Acid → (4S,5R,6R,18R)-4,5-dihydroxy-3,8,8,15,15,18-hexamethyl-7,9-dioxapentacyclo[11.5.1.01,5.06,11.014,16]nonadeca-2,11-dien-19-one

Participants

Reaction Conditions

Reaction Steps

Dry ingenol (15.00 g, 90%, 38.75 mmol) was dissolved in acetone (630 mL) with stirring, and the solution was heated to 45° C. A solution of methanesulfonic acid (0.745 g, 7.75 mmol) in acetone (10 mL) was added during 5 seconds. The solution was stirred at 45° C. for an additional 95 seconds, before a solution of triethylamine (1.35 mL, 0.98 g, 9.69 mmol) in acetone (10 mL) was added during 5 seconds. The mixture was cooled to 20° C., and ethyl acetate (500 mL) was added. Most of the reaction solvent (650 mL) was distilled off under vacuum. Water (200 mL) was added to the remaining solution, and the mixture was agitated for 2 minutes. The water layer was removed, and the water wash was repeated once before the organic phase was concentrated under vacuum. The crude product contained 84% of the title compound as determined by 1H NMR spectroscopy. The residue was dissolved in toluene (75 mL) by heating to reflux temperature followed by slow cooling to 5° C. After 4 hours standing, the formed crystals were filtered off, rinsed with 5° C. toluene (2×5 mL) and dried under vacuum at 20° C. until constant weight. After 18 hours, ingenol-5,20-acetonide (8.97 g) was obtained.

Provenance & Evidence