Strategies toward the total synthesis of pretubulysin, its fragments and analogues

Pretubulysin, a biosynthetic precursor of tubulysins, exhibits potent cytotoxicity in subnanomolar range toward several cancer cell lines. This natural product (extracted from myxobacterial strains) along with its derivatives plays an important role in the development of a variety of antitumor drugs. In this review, natural and synthetic pretubulysins, as well as their synthetic analogues have been discussed in detail.