An efficient, general asymmetric synthesis of carbocyclic nucleosides: application of an asymmetric aldol/ring-closing metathesis strategy.
A general and efficient synthesis of carbocyclic and hexenopyranosyl nucleosides has been developed. The strategy combines three key transformations: an asymmetric aldol addition to establish the relative and absolute configuration of the pseudosugar, a ring-closing metathesis to construct the pseudosugar ring, and a Trost-type palladium(0)-mediated substitution to assemble the pseudosugar and the aromatic base. Carbovir, abacavir, and their 2'-methyl derivatives as well as hexenopyranosyl nucleoside analogues have been prepared by this sequence.
Crimmins
M T
MT
Venable and Kenan Laboratories of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290, USA. crimmins@email.unc.edu
King
B W
BW
Zuercher
W J
WJ
Choy
A L
AL
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry; D015224:Dideoxynucleosides / Q000138:chemical synthesis / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D013055:Spectrophotometry, Infrared; D000099227:Abacavir
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D009705:Nucleosides; D000099227:Abacavir; C057503:carbovir