SULFATION OF BETULIN 3-PROPIONATE WITH SULFAMIC ACID IN N,N-DIMETHYLFORMAMIDE MEDIUM

A new efficient method for the sulfation of betulin 3-propionate using sulfamic acid –urea mixture in N,N-dimethylformamide medium was developed. This method of synthesis allows to exclude the use of such aggressive sulfating reagents as sulfur dioxide, chlorosulfonic and sulfuric acid. As a result, 28-sulfates of betulin 3-propionate were obtained as ammonium salt, acidic form, potassium salt and sodium salt in 91, 89, 89, 90% yields, respectively. The composition of the obtained samples of 28-sulfate 3-propionate betulin was confirmed by elemental analysis, the sulfur content ranged from 5.03 to 5.32%. The structure of the initial and sulfated betulin 3-propionate was studied by FTIR and 13C NMR spectroscopy. The introduction of sulfate groups into the molecule of betulin 3-propionate was confirmed by the appearance of new absorption bands in the FTIR spectra at 830–833 cm-1 and at 1225–1227 cm-1, which corresponds to the stretching vibrations υ(C–O–S) and to the asymmetric stretching vibrations υas(O=S=O), respectively. It was shown by 13C NMR method that the initial betulin 3-propionate has a C28 carbon atom signal at a chemical shift of 60.6 ppm, while the synthesized as the sodium salt of betulin 3-propionate 28-sulfate has a C28 carbon atom signal at a chemical shift of 66.0 ppm. This indicates a complete substitution of the hydroxyl group of betulin 3-propionate for the sulfate group.