Syntheses and reactions of 1',2'-unsaturated 2',3'-seconucleoside analogues

Article abstract of DOI:10.1002/hlca.19950780714

The 1',2'-unsaturated 2',3'-secoadenosine and 2',3'-secouridine analogues were synthesized by the regioselective elimination of the corresponding 2',3'-ditosylates, 2 and 18, respectively, under basic conditions. The observed regioselectivity may be explained by the higher acidity and, hence, preferential elimination of the anomeric H-C(1') in comparison to H-C(4'). The retained (tol-4-yl)sulfonyloxy group at C(3') of 3 allowed the preparation of the 3'-azido, 3'-chloro, and 3'-hydroxy derivatives 5-7 by nucleophilic substitution. ZnBr₂ in dry CH₂Cl₂ was found to be successful in the removal (85%) of the trityl group without any cleavage of the acid-sensitive, ketene-derived N,O-ketal function. In the uridine series, base-promoted regioselective elimination (→ 19), nucleophilic displacement of the tosyl group by azide (→ 20), and debenzylation of the protected N(3)-imide function gave 1',2'-unsaturated 5'-O-trityl-3'-azido-secouridine derivative 21. The same compound was also obtained by the elimination performed on 2,2'-anhydro-3'-azido-3'-deoxy-5'-O-trityl-2',3'-secouridine (22) that reacted with KO(t-Bu) under opening of the oxazole ring and double-bond formation at C(1').