Structural modification of the antibiotic pleuromutilin has afforded several derivatives with considerably enhanced activity against bacteria and mycoplasmas, and has permitted conclusions to be reached about structure-activity relationships. The carbonyl group in the five-membered ring and the hydroxyl group at C₁₁ seem to be essential for activity. The vinyl group can be hydrogenated without loss of activity. Chemical modification at C₁₄ offers the most possibilities for achieving the best activity and solubility properties. Mutilin, and other compounds with a free OH at C₁₄, are inactive. It was shown that mutilin esters of substituted thioglycolic acids had distinctly superior MIC values, especially in combination with a tertiary amino group in the side chain, the latter group of derivatives having MIC values better than pleuromutilin by a factor of more than 10. Further variation within this group led to the development of 14-deoxy-14-[(2-diethylaminoethyl) thioacetoxy]-mutilin hydrogen fumarate
(81.723 hfu, tiamulin) for extensive investigation of its chemotherapeutic potential.