Cyclization of synthetic seco-proansamitocins to ansamitocin macrolactams by actinosynnema pretiosum as biocatalyst

摘要

Ring closure is possible with seco-proansamitocin and two activated SNAC esters, which can be processed to ansamitocin P3 and 19-deschloro-20-demethoxy AP-3, respectively, by an AHBA-blocked mutant of Actinosynnema pretiosum. This work sheds light on the synthetic potential of macrolactamizing amide synthases. The new ansamitocin derivative showed similar to enhanced antiproliferative activity against several cancer cell lines relative to AP-3.