title: A straightforward approach towards cyclic photoactivatable tubulysin derivatives.
abstract: The development of a new photolabile protecting group containing an additional allyl functionality allows the synthesis of cyclic photoactivatable natural products. Cyclization occurs between the allyl moiety in the protecting group and a second double bond in the target molecule by means of ring-closing metathesis. Cyclization should increase the metabolic stability towards proteases. On the other hand, the conformational change should cause diminished biological activity. As illustrated for tubulysin derivatives, cyclic and photoactivatable drug candidates can easily be obtained in only two steps from simple building blocks through Ugi reaction and ring-closing metathesis. The photolabile protecting group is introduced by means of the isocyanide component during the Ugi reaction.
authors.affiliation: Institute for Organic Chemistry, Saarland University, P.O. Box 151150, 66041 Saarbrücken (Germany) http://www.uni-saarland.de/fak8/kazmaier.
authors.forename: Judith
authors.initials: J
authors.lastname: Hoffmann
authors.forename: Uli
authors.initials: U
authors.lastname: Kazmaier
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010782:Photolysis
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D009842:Oligopeptides; C510756:tubulysin A; C575012:pretubulysin
keywords: antitumor agents; natural products; photoactivation; pretubulysin; tubulysin