The interplay between mutasynthesis and semisynthesis: Generation and evaluation of an ansamitocin library

Working hand in hand! The synthetic power of three mutant strains that produce ansamitocin and geldanamycin is combined with chemical synthesis, thus leading to 27 new ansamitocin derivatives. Structure-activity studies show that the N of the carbinolamide moiety is not important for cytotoxic activity but the α orientation of the OH group at C9 is key [see structures; chemical synthesis (red), mutasynthesis (blue), biosynthesis (black)].