The chemistry and biology of the maytansinoid antitumor agents

Maytansine (1) and its congeners have been isolated from higher plants, mosses and from an Actinomycete, Actinosynnema pretiosum. The ansamitocins P-1 to P-4 (11b–11e) are structurally closely related macrolactam antibiotics which have been obtained from bacterial sources, mainly A. pretiosum. Many of these compounds are antitumor agents of extraordinary potency. Detailed structure–activity relationship (SAR) studies have been hampered by the accessibility of analogues in sufficient amounts. The present review focuses on several synthetic approaches towards the maytansinoids which include total synthesis, semisynthesis and mutational biosynthesis utilising genetically engineered microorganisms.