Tubulysin Synthesis Featuring Stereoselective Catalysis and Highly Convergent Multicomponent Assembly
Thimmalapura M Vishwanatha1, Ben Giepmans2, Sayed K Goda3
1Department of Drug Design, University of Groningen, A. Deusinglaan 1, 9700 AD Groningen, The Netherlands.
Abstract:
A concise and modular total synthesis of the highly potent N14-desacetoxytubulysin H (1) has been accomplished in 18 steps in an overall yield of up to 30%. Our work highlights the complexity-augmenting and route-shortening power of diastereoselective multicomponent reaction (MCR) as well as the role of bulky ligands to perfectly control both the regioselective and diastereoselective synthesis of tubuphenylalanine in just two steps. The total synthesis not only provides an operationally simple and step economy but will also stimulate major advances in the development of new tubulysin analogues.
Related Concept Videos
Ziegler–Natta Chain-Growth Polymerization: Overview
Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
Biosynthesis in Bacteria
Protein Complex Assembly
Many viruses self-assemble into a fully functional unit using the infected host cell to...


