m-Chloroperbenzoic acid → Catharanthine N-oxide

Participants

Reaction Steps

To a solution of catharanthine (201 mg, 0.60 mmol) in methylene chloride (40 ml) at -15° C. was added a solution of m-chloroperbenzoic acid (111 mg, 0.65 mmol) and the solution stirred for 15 min. To the catharanthine N-oxide thus formed was added a solution of vindoline (270 mg, 0.59 mmol) in methylene chloride. The atmosphere in the reaction flask was then replaced with nitrogen and the remainder of the coupling carried out in this inert atmosphere. Trifluoroacetic anhydride (0.41 ml, 3.01 mmol) was added to the stirred solution maintained at -15° C. After 22 hours this mixture was added to a solution of sodium borohydride in ethanol. After the initial vigorous evolution of gas, water and additional methylene chloride was added to the reaction mixture. The organic phase was separated and the aqueous layer washed with a second portion of methylene chloride. The organic portions were combined and washed with a solution of K2CO3. The organic phase was separated and dried with Na2SO4. The solvent was evaporated in vacuo and the residue dissolved in hot acetone. The solution was cooled and crystals of 3'4'-dehydrovinblastine were isolated. The mother liquors from the crystallization were chromatographed on silica gel plates using methanol-ethyl acetate as the eluting solvent. The combined fractions of 3'4'-dehydrovinblastine, mp 171°-173° obtained from these purifications amounted to 226 mg (0.29 mmol). Calc. for C46H56O8N4 : 792.410. Found: 792.405.

Provenance & Evidence