Concise Total Synthesis of N¹⁴-Desacetoxytubulysin H

Access to analogues within the highly cytotoxic natural product family of tubulysins has previously required lengthy routes involving multiple functional group manipulations that is costly and time intensive on scale. A concise and modular total synthesis of the highly potent N¹⁴-desacetoxytubulysin H has been accomplished in a short sequence from commercially available building blocks. Our work highlights the complexity augmenting and route shortening power of multicomponent reaction (MCR) as well as the role of catalysts in controlling diastereoselectivity. Our operationally simple and s tep economical total synthesis can be easily performed on gram scale without compromising the yield.