A straightforward stereoselective synthesis of D- and L-5-hydroxy-4-hydroxymethyl-2-cyclohexenylguanine.
A novel and facile synthesis of 5-hydroxy-4-hydroxymethyl-2-cyclohexenylguanine 1 is described. The key steps involve a Diels-Alder reaction of ethyl (2E)-3-acetyloxy-2-propenoate 2 as dienophile with Danishefsky's diene 3 to build up the six-membered ring skeleton, a Fraser-Reid reductive rearrangement of the adduct using LiAlH(4), and base-moiety introduction using a Mitsunobu reaction. Optically pure D- and L-1 were obtained via resolution of intermediate 7 with (R)-(-)-methylmandelic acid. The synthetic procedure toward racemic 1 consists of only five steps and has proven to be highly efficient toward the synthesis of cyclohexenyl nucleosides.
Wang
J
J
Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Morral
J
J
Hendrix
C
C
Herdewijn
P
P
D017607:Aluminum Compounds; D000998:Antiviral Agents / Q000138:chemical synthesis*; D002851:Chromatography, High Pressure Liquid; D006147:Guanine / Q000031:analogs & derivatives / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D018020:Lithium Compounds; D009682:Magnetic Resonance Spectroscopy; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
C443724:5-hydroxy-4-hydroxymethyl-2-cyclohexenylguanine; D017607:Aluminum Compounds; D000998:Antiviral Agents; D007202:Indicators and Reagents; D018020:Lithium Compounds; D006147:Guanine; C042073:lithium aluminum hydride