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Syntheses and Reactions of 1′,2′‐Unsaturated 2′,3′‐Seconucleoside Analogues
Author(s) -
Vrček Valerije,
Čaplar Vesna
Publication year - 1995
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19950780714
Subject(s) - chemistry , regioselectivity , ketene , azide , nucleophile , medicinal chemistry , stereochemistry , nucleophilic addition , oxazole , trimethylsilyl azide , imide , nucleophilic substitution , organic chemistry , catalysis
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 HC(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. ZnBr 2 in dry CH 2 Cl 2 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′‐azido‐3′‐deoxy‐5′‐ O ‐2′,3′‐secouridine ( 22 ) that reacted with KO( t ‐Bu) under opening of the oxazole ring and double‐bond formation at C(1′).