A Versatile Enantioselective Strategy Towardl-C-Nucleosides:  A Total Synthesis ofl-Showdomycin

Abstract

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.

Metal‐Catalyzed Enantioselective Allylation in Asymmetric Synthesis

“…[237] The reaction is quite general: a similar reaction of 243 a with 244 b afforded 245 ab with 92 % ee. [238] The reaction of 1,4-dibenzoyloxy-2-cyclopentene (243 b), 1,4-diacetoxy-2-cyclopentene (243 c), 1,4-dibenzoyloxy-2-cyclohexene (243 e) with various carbon nucleophiles produced the related products 245 b, 245 c, and 245 e with high enantioselectivity (! 95 % ee, Table 9).…”

Synthesis and Antiviral Evaluation of Novel 6′(α)‐Methyl‐Branched Carbovir Analogues

“…Compound 9 was coupled with adenine and cytosine anions generated by NaH/DMSO using the [tris(dibenzylidene-acetone)-dipalladium(0)-chloroform] [18,19] adduct to give the compounds 10 and 11 (Scheme 2). The required β-stereochemistry of the nucleosides 10 and 11 was successfully controlled from the β-configuration of compounds 9 via a Pd(0) catalyzed πϪallyl complex mechanism [20,21]. Compounds 10 and 11 were desilylated by treating them with tetrabutylammonium fluoride (TBAF) to give the final nucleosides 12 and 13 in high yields.…”

Asymmetric Allylic Alkylation, an Enabling Methodology

“…Focusing on a synthesis of its mirror image, both paths a and b were examined as shown in eq 8 (Scheme 13). 29 Although the standard ligand 31 functioned well using the sulfone 63 as the nucleophile, the ee's dropped to 78% using the substituted malonate. Switching to the an- thracene-derived ligand 65 restored the ee to 90%.…”