The Multiple Multicomponent Approach to Natural Product Mimics: Tubugis, N-Substituted Anticancer Peptides with Picomolar Activity

The synthesis of a new generation of highly cytotoxic tubulysin analogues (i.e., tubugis) is described. In the key step, the rare, unstable, and synthetically difficult to introduce tertiary amide–N,O-acetal moiety required for high potency in natural tubulysins is replaced by a dipeptoid element fo...

Full description

Saved in:
Bibliographic Details
Published in:Journal of the American Chemical Society 2011-05, Vol.133 (20), p.7692-7695
Main Authors: Pando, Orlando, Stark, Sebastian, Denkert, Annika, Porzel, Andrea, Preusentanz, Rainer, Wessjohann, Ludger A
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Biological Products - chemistry
Dose-Response Relationship, Drug
Molecular Mimicry
Peptides - chemistry
Peptides - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The synthesis of a new generation of highly cytotoxic tubulysin analogues (i.e., tubugis) is described. In the key step, the rare, unstable, and synthetically difficult to introduce tertiary amide–N,O-acetal moiety required for high potency in natural tubulysins is replaced by a dipeptoid element formed in an Ugi four-component reaction. Two of the four components required are themselves produced by other multicomponent reactions (MCRs). Thus, the tubugis represent the first examples of the synthesis of natural-product-inspired compounds using three intertwined isonitrile MCRs.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja2022027