title: The multiple multicomponent approach to natural product mimics: tubugis, N-substituted anticancer peptides with picomolar activity.
abstract: 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.
authors.affiliation: Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle (Saale), Germany.
authors.forename: Orlando
authors.initials: O
authors.lastname: Pando
authors.forename: Sebastian
authors.initials: S
authors.lastname: Stark
authors.forename: Annika
authors.initials: A
authors.lastname: Denkert
authors.forename: Andrea
authors.initials: A
authors.lastname: Porzel
authors.forename: Rainer
authors.initials: R
authors.lastname: Preusentanz
authors.forename: Ludger A
authors.initials: LA
authors.lastname: Wessjohann
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D010455:Peptides