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 β-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.
|Original language||English (US)|
|Number of pages||14|
|Journal||Journal of Medicinal Chemistry|
|State||Published - Jul 1 1995|
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Drug Discovery