J Med Chem. 1995 Jul 7;38(14):2714-27.

Synthesis and biochemical evaluation of adenosylspermidine, a nucleoside-polyamine adduct inhibitor of spermidine synthase.

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Department of Chemistry, University of Michigan, Ann Arbor 48109-1055, USA.

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.

PMID:: 7629810; [PubMed - indexed for MEDLINE]

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Synthesis and biochemical evaluation of adenosylspermidine, a nucleoside-polyami...
Synthesis and biochemical evaluation of adenosylspermidine, a nucleoside-polyamine adduct inhibitor of spermidine synthase.
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Synthesis and biochemical evaluation of adenosylspermidine, a nucleoside-polyamine adduct inhibitor of spermidine synthase.

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