Enantioselective Synthesis of Homo-N-Nucleosides Containing a 1,4-Dioxane Sugar Analog.docVIP

Molecules 2008, 13,2962-2974; DOI: 10.3390/moleculeOPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Enantioselective Synthesis of Homo-N-Nucleosides Containing a 1,4-Dioxane Sugar Analog Qiang Yu and Per Carlsen * Department of Chemistry, Norwegian University of Science and Technology (NTNU), N-7491 Trondheim, Norway; E-mail: qiang@nt.ntnu.no * Author to whom correspondence should be addressed; E-mail: per.carlsen@chem.ntnu.no; Fax: +47 Received: 3 September 2008; in revised form: 30 October 2088 / Accepted: 7 November 2008 / Published: 3 December 2008 Abstract: A dioxane homo-sugar analog, (2S,5S)-and (2R,5S)-5-[(4S)-2,2-dimethyl-1,3- dioxolan-4-yl]-2-iodomethyl-1,4-dioxane was prepared from (2R,3R)-dimethyl tartrate, and further elaborated into the corresponding homo-N-nucleoside analogs by its reactions with uracil and adenine, respectively. Keywords: Sugar analog; Nucleoside analogs; Homo-N-Nucleoside; 1,4-Dioxane, Hetero- cycles. Introduction There has been an increasing interest in the synthesis of nucleoside analogs with modifications of the sugar moiety for the purpose of obtaining new antiviral and antitumor agents [1-3]. A well known class of modified nucleosides are the homo-N- and C-glycosidic nucleosides [4-8] The insertion of a methylene group between the heterocyclic base and the sugar moiety results in a more flexible structure, and due to the lack of an anomeric acetal position, these nucleosides are in general resistant to enzymatic degradation [8]. For these reasons, we decided to pursue the synthesis of nucleoside analogs, however, based on the conformationally more flexible, optically active homo-1,4-dioxane sugar analogs. The objective was thus to construct novel homo-N-nucleoside analogs containing a 1,4-  Molecules 2008, 13 2963 dioxane sugar moiety. A representative structure is shown in Figure 1, where the 1,4-dioxane homo- sugar a