To synthesize Gamithromycin from 9-deoxy-8a-aza-8a-homoerythromycin A as a precursor: Using dichloromethane as the reaction solvent, 9-deoxy-8a-aza-8a-homoerythromycin A undergoes an SN2 substitution reaction with bromopropane to obtain the final product Gamithromycin, with yields and contents of 66.1% and 63.87%, respectively. Alternatively, Gamithromycin can be synthesized using a propionaldehyde-cyanoborohydride hydrogenation method, with 9-deoxy-8α-aza-8α-homoerythromycin A as an intermediate, with a yield of 38.1%. Another method involves high-pressure hydrogenation using erythromycin 9,12-imine ether as a raw material and 5% Pt/C as a catalyst. Acetic acid is added, followed by the addition of propionaldehyde and acetic acid to obtain the target product Gamithromycin, with yields and purities of 79.0% and 88.9%, respectively.
Gamithromycin is a semi-synthetic macrocyclic lactone belonging to the azalide class derived from erthyromycin, typified by azithromycin. The synthesis of gamithromycin involves a ring expansion using a Beckmann rearrangement to produce the 15-membered dibasic macrolide. Gamithromycin provides a broader spectrum of action, higher acid stability and improved bioavailability compared to older analogues of the erythromycin class and has been exclusively developed for animal health applications.
