A straightforward stereoselective synthesis of D- and L-5-hydroxy-4-hydroxymethyl-2-cyclohexenylguanine. |
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Authors: | J Wang J Morral C Hendrix P Herdewijn |
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Institution: | Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium. |
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Abstract: | 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. |
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