Sulfation of Betulin 3-Propionate with Sulfamic Acid in N,N-Dimethylformamide Medium
摘要
Objective: The study aims to develop an efficient method for the sulfation of betulin 3-propionate using a sulfamic acid–urea mixture in N,N-dimethylformamide medium. The goal is to synthesize various derivatives of betulin 3-propionate sulfates, avoiding the use of aggressive sulfating reagents such as sulfur dioxide and sulfuric acid. Methods: Betulin 3-propionate was sulfated with a sulfamic acid–urea mixture in N,N-dimethylformamide. The reaction was conducted at temperatures of 45–50°C for 3 h. The sulfated products (ammonium salt, acidic form, potassium salt, and sodium salt) were isolated by diluting the reaction mixture with water and extracting with butanol. The yield of the sulfates was determined, and the compositions of the products were confirmed by elemental analysis. The structure of the sulfated products was analyzed using FT-IR and 13C NMR spectroscopy. Results and Discussion: The sulfation process successfully produced 28-sulfates of betulin 3-propionate in high yields (91, 89, 89, and 90% for ammonium salt, acidic form, potassium salt, and sodium salt, respectively). The composition of the obtained sulfates was confirmed by elemental analysis, with sulfur content ranging from 5.03 to 5.32%. The FT-IR spectra showed characteristic absorption bands for the sulfate group at 830–833 cm–1 (C–O–S) and 1225–1227 cm–1 (O=S=O). The 13C NMR analysis confirmed the complete substitution of the hydroxyl group at C28 with the sulfate group, as evidenced by a chemical shift from 60.6 ppm (in betulin 3-propionate) to 66.0 ppm (in the sodium salt of the sulfate). Conclusions: The sulfation of betulin 3-propionate using a sulfamic acid–urea mixture in N,N-dimethylformamide is an efficient method that avoids the use of aggressive reagents. The synthesis of betulin 3-propionate 28-sulfate derivatives was successful, and the structure of the sulfates was confirmed by FT-IR and 13C NMR spectroscopy. This method offers a promising approach for the modification of betulin derivatives for potential bioactive applications.