Abstract
Nucleosides containing five-membered deoxy-carbohydrates in the glycosidic part, such as zalcitabine, 2'.3'-dideoxyuridine, stavudine, are widely used in acquired immunodeficiency syndrome (AIDS). A number of 2'.3'-dideoxynucleosides is an effective inhibitor of type-1 immunodeficiency virus (HIV-1) in humans. Levoglucosenone and cyrene (dihydrolevoglucosenone) are unique compounds, optically pure ketones of carbohydrate nature obtained from renewable bio-raw materials and available by pyrolysis of any cellulose-containing materials. They are promising carbohydrates for the production of modified nucleosides; in addition, they are commercially available. Based on levoglucosenone, we synthesized chiral carbohydrate blocks for dideoxy-nucleosides, namely, tertbutyldimethylsilyl derivatives of (S)-5-(hydroxymethyl)-2.5-dihydrofuran-2-ol and (S)-5-(hydroxymethyl)tetrahydrofuran-2-ol. At the first stage of the synthesis, a one-stage modification of the pyranose form of levoglucosenone and cyrene to γ-butanolides was carried out by Bayer-Williger oxidation using H2O2 in the presence of Amberlyst-15 in water. The reduction of unprotected hydroxymethyl-γ-butanolide obtained from cyrene to lactol was studied. The reduction of γ-butanolide by the action of BH3·SMe2, Red-Al, or LiAlH(OtBu)3 in THF at 0° C leads mainly to triol, the product of complete reduction. The desired lactol was obtained using iBu2AlH at -78°C in CH2Cl2 in good yield. Raising the reaction temperature to 0° C led to a decrease in the yield of lactol. It has been established that (S)-5-(hydroxymethyl)-tetrahydrofuran-2-ol exists in both five-membered and six-membered forms. Due to the fact that the target lactols easily undergo a transition from the furanose to the pyranose form, they are not used to produce nucleosides. Therefore, we have studied the approach to the synthesis of stable five- membered lactols. For this purpose, in lactones obtained by the Bayer-Williger reaction, the primary hydroxyl group was blocked using TBSCl. Subsequent reduction of the esters using iBu2AlH gave lactols that existed exclusively in the furanose form. The total yield of the target (S)-5-(hydroxymethyl)-2.5-dihydrofuran-2-ol obtained from levoglucosenone was 39% and (S)-5-(hydroxymethyl)-tetrahydrofuran-2-ol obtained from cyrene was 65%.
Published Version
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