Discovery of a Potent Adenine-Benzyltriazolo-Pleuromutilin Conjugate with Pronounced Antibacterial Activity against MRSA.

Conjugation of pleuromutilin is an attractive strategy for the development of novel antibiotics and the fight against multiresistant bacteria as the class is associated with low rates of resistance and cross-resistance development. Herein, the preparation of 35 novel (+)-pleuromutilin conjugates is reported. Their design was based on a synthetically more efficient benzyl adaption of a potent lead but still relied on the Cu(I)-catalyzed alkyne-azide [3 + 2] cycloaddition for conjugation onto pleuromutilin.