Studies on 2'-alpha-C-carboxyalkyl nucleosides and their application to a stereocontrolled nucleobase exchange process.
The ability of 2'-alpha-C-carboxyalkyl nucleosides to undergo an unusual two-step stereocontrolled nucleobase exchange process has been investigated. Upon silylation a protected 2'-deoxy-2'-alpha-C-(carboxymethyl)uridine derivative can undergo intramolecular displacement of the uracil base, by the 2'-carboxylic acid group, to form a pentofuranosyl gamma-lactone. Under identical conditions the homologous 2'-deoxy-2'-alpha-C-(carboxyethyl)uridine derivative does not yield the corresponding delta-lactone, but undergoes elimination of uracil to give the corresponding glycal. The pentofuranosyl gamma-lactone is a good substrate for nucleoside synthesis by the Vorbrüggen procedures and undergoes completely stereoselective ring opening with either pyrimidine or purine silylated nucleobases to give novel 2'-C-carboxymethyl beta-nucleosides in moderate to high yield.
Fehring
Volker
V
Department of Chemistry, University of Liverpool, Crown St., Liverpool, UK L69 7ZD.
Knights
Sally
S
Chan
Mai-Yee
MY
O'Neil
Ian A
IA
Cosstick
Richard
R
D002625:Chemistry, Organic / Q000379:methods; D007783:Lactones / Q000737:chemistry*; D013058:Mass Spectrometry; D008956:Models, Chemical; D009705:Nucleosides / Q000737:chemistry*; D014498:Uracil / Q000737:chemistry
D007783:Lactones; D009705:Nucleosides; D014498:Uracil