476490-34-3Relevant academic research and scientific papers
A highly stereoselective samarium diiodide-promoted aldol reaction with 1′phenylseleno-2′-keto nucleosides. Synthesis of 1′α-branched uridine derivatives
Kodama, Tetsuya,Shuto, Satoshi,Ichikawa, Satoshi,Matsuda, Akira
, p. 7706 - 7715 (2002)
Since 1′-branched nucleosides are biologically important targets in medicinal chemistry, more efficient methods for preparing them are required. The 1′α-branched uridine derivatives were successfully synthesized via a samarium diiodide (SmI2)-promoted aldol reaction. Treatment of the 1′α-phenylseleno-2′-ketouridine derivative 6, readily prepared from uridine, with SmI2 at -78 °C in THF reductively cleaved the anomeric Se-C bond to generate the corresponding samarium enolate, which was highly stereoselectively condensed with aldehydes, such as PhCHO, MeCHO, i-PrCHO, or (CH2O)n, to give the corresponding 1′α-1″S-branched products 12a-d. This is the first time an enolate has been generated by reductively cleaving a C-Se bond. The highly selective stereochemical results suggest that the aldol reaction proceeds via a chelation-controlled transition state. When an excess of aldehyde was used and the reaction mixture was gradually warmed, the tandem aldol-Tishchenko reaction proceeded to give the "arabino-type" nucleosides 14a-c, having a 2′-"up" hydroxyl and 1′α-1″S-branched chain. 1′α-Hydroxymethyluridine (21), which is the uracil version of the antitumor antibiotic angustmycin C, was synthesized from the aldol reaction product 10.
