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ID: ALA1128469
Journal: J Med Chem
Title: Synthesis and biochemical evaluation of adenosylspermidine, a nucleoside-polyamine adduct inhibitor of spermidine synthase.
Authors: Lakanen JR, Pegg AE, Coward JK.
Abstract: The synthesis of a new class of multisubstrate adduct inhibitors of polyamine biosynthesis has been investigated. The first target compound, designed to inhibit spermidine synthase, was obtained and proved to be a very potent inhibitor of that enzyme. Two synthetic routes to effect the coupling of the polyamine spermidine to the nucleoside adenosine were studied. The first route involved a proposed Wittig or Julia olefination reaction to form the critical 5'-6' carbon-carbon bond between the nucleoside and polyamine moieties. This route failed due to a facile beta-elimination of a portion of the side chain from a carbanion intermediate during either coupling reaction. A second route involved a reductive amination approach and proved to be successful. The new inhibitor, given the trivial name adenosylspermidine, is the most potent inhibitor of spermidine synthase prepared to date.
CiteXplore: 7629810
DOI: 10.1021/jm00014a023