A highly stereoselective samarium diiodide-promoted aldol reaction with 1'-phenylseleno-2'-keto nucleosides. Synthesis of 1'alpha-branched uridine derivatives.
Since 1'-branched nucleosides are biologically important targets in medicinal chemistry, more efficient methods for preparing them are required. The 1'alpha-branched uridine derivatives were successfully synthesized via a samarium diiodide (SmI(2))-promoted aldol reaction. Treatment of the 1'alpha-phenylseleno-2'-ketouridine derivative 6, readily prepared from uridine, with SmI(2) at -78 degrees 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 (CH(2)O)(n)(), to give the corresponding 1'alpha-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'alpha-1' 'S-branched chain. 1'alpha-Hydroxymethyluridine (21), which is the uracil version of the antitumor antibiotic angustmycin C, was synthesized from the aldol reaction product 10.
Kodama
Tetsuya
T
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
Shuto
Satoshi
S
Ichikawa
Satoshi
S
Matsuda
Akira
A
D000447:Aldehydes / Q000737:chemistry*; D007454:Iodides / Q000737:chemistry*; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry*; D010084:Oxidation-Reduction; D012493:Samarium / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013696:Temperature; D014529:Uridine / Q000031:analogs & derivatives* / Q000737:chemistry*
D000447:Aldehydes; D007454:Iodides; D009705:Nucleosides; D012493:Samarium; C409809:samarium diiodide; D014529:Uridine