| Abstract
| - Since 1‘-branched nucleosides are biologically important targets in medicinal chemistry, moreefficient methods for preparing them are required. The 1‘α-branched uridine derivatives weresuccessfully synthesized via a samarium diiodide (SmI2)-promoted aldol reaction. Treatment ofthe 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 samariumenolate, 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 firsttime an enolate has been generated by reductively cleaving a C−Se bond. The highly selectivestereochemical results suggest that the aldol reaction proceeds via a chelation-controlled transitionstate. When an excess of aldehyde was used and the reaction mixture was gradually warmed, thetandem aldol-Tishchenko reaction proceeded to give the “arabino-type” nucleosides 14a−c, havinga 2‘-“up” hydroxyl and 1‘α-1‘ ‘S-branched chain. 1‘α-Hydroxymethyluridine (21), which is the uracilversion of the antitumor antibiotic angustmycin C, was synthesized from the aldol reaction product10.
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