Methyl p-toluenesulfonate → Methylamphotericin B

Participants

Reaction Steps

To 1.5 mL of anhydrous DMF in a 3 mL flask was added p-chlorobenzaldehyde (0.0663 g, 4.72×E-4 moles). While purging the flask with nitrogen, Amphotericin B (0.1511 g, 1.51×E-4 moles) is slowly sifted into the vigorously stirred solution over 3 to 4 minutes. All the solid dissolved within 15 minutes and stirring was continued for an additional 30 minutes. At this point all the Amphotericin B was converted to the soluble N-p-chlorobenzylidine derivative. To the clear yellow solution was added N,N-diisopropylethylamine (0.079 mL, 4.53×E-4 moles) followed by methyl p-toluenesulfonate (0.0843 g, 4.53×E-4 moles). The reaction mixture was allowed to stir for 22 hours at ambient temperature and a small aliquot of the reaction mixture was removed and analyzed by reverse phase HPLC. The analysis indicated no unreacted Amphotericin B was present in the reaction mixture. The major component of the product mixture was Amphotericin B methyl ester. The mixture was added to 15 mL of methyl tert.-butyl ether and a yellow solid precipitated. The solid was separated by centrifugation and washed once with 10 mL of methyl tert.-butyl ether. Drying under high vacuum afforded 0.184 g of p-chlorobenzylidine Amphotericin B methyl ester.

Provenance & Evidence