Multigram-scale synthesis of an experimental antibiotic, Lolamicin and its intermediate

Herein, we report a multigram-scale synthesis of the recently discovered antibiotic Lolamicin. To enable rapid analogue generation for lead optimisation, a key intermediate bearing three sites of diversification was designed and prepared on a scale of more than 100 grams. Using ten readily accessible substituents at each position, this strategy potentially can provide 1000 compounds. The synthetic route features operationally simple procedures and avoids chromatographic purification, highlighting its practicality and scalability.