Diastereoselective Synthesis of (1, 3‐Dioxan‐4‐yl)pyrimidine and Purin Nucleoside Analogues. Issue 6 (14th January 2015)

• Record Type: Journal Article
• Authors: Battisti, Umberto M.; Sorbi, Claudia; Quotadamo, Antonio; Franchini, Silvia; Tait, Annalisa; Schols, Dominique; Jeong, Lak Shin; Lee, Sang Kook; Song, Jayoung; Brasili, Livio
• Is Part Of: European journal of organic chemistry. Issue 6(2015)
• Page Start: 1235
• Page End: 1245
• Publication Date: 2015-01-14
• Subjects: Nucleoside analogues -- Nitrogen heterocycles -- Regioselectivity -- Diastereoselectivity; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.201403473
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: (1, 3‐Dioxan‐4‐yl)‐substituted nucleoside analogues, higher homologues of antiviral and anticancer 1, 3‐dioxolanes, were prepared from the key intermediate (4‐acetoxy‐1, 3‐dioxan‐2‐yl)methyl benzoate and silylated bases. Glycosylation, carried out under Vorbrüggen conditions in the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf) as a catalyst, afforded the desired compounds with high stereoselectivity and regioselectivity, with only the desired β‐anomeric N‐1 pyrimidine and N‐9 purin nucleosides being obtained. 1 H NMR experiments established that the β‐anomers were diequatorial, and this assignment was confirmed by single‐crystal X‐ray diffraction. Despite their structural similarities with natural nucleosides, none of the synthesized nucleosides showed antiviral activity. Abstract : The first regioselective and diastereoselective synthesis of 1, 3‐dioxan‐4‐yl‐substituted nucleoside analogues is reported. (4‐Acetoxy‐1, 3‐dioxan‐2‐yl)methyl benzoate is regioselectively glycosylated under Vorbrüggen conditions to afford the desired products in good yields. The regioselectivity might be due to the existence of thermodynamically controlled intermediates.