233679-10-2Relevant academic research and scientific papers
A versatile enantioselective strategy toward L-C-nucleosides: A total synthesis of L-showdomycin
Trost, Barry M.,Kallander, Lara S.
, p. 5427 - 5435 (2007/10/03)
Strategies for the synthesis of nucleosides that can provide either L or D isomers become more important as a result of the increasing number of such compounds that are therapeutically useful. The lower toxicity and reduced susceptibility toward metabolism of the L isomers make them particularly interesting. A strategy toward the C-nucleoside analogues has been explored in the context of the synthesis of L-showdomycin. The route involves an asymmetric desymmetrization using palladium catalysis of cis-2,5-diacyloxy- 2,5-dihydrofurans available in one step from furan, with carbon nucleophiles. Nucleophilic synthons for a maleimide unit and a methoxycarbonyl unit have been designed. Two sequential palladium-catalyzed reactions introduce both substituents with excellent chemo-, regio-, diastereo-, and enantioselectivity. The presence of a double bond in this doubly alkylated compound at C-3 and C-4 allows easy structural variation. The use of an ester as a hydroxymethyl precursor also introduces a diversity element as well as having importance in its own right. The successful completion of a synthesis of L-showdomycin validates this approach as a viable strategy to C- nucleosides.
