Skip to main content
SLU publication database (SLUpub)
Research article - Peer-reviewed, 1993

Synthesis of Diastereomerically Pure 4'-Alkoxy-alpha-(L)- and -beta(D)-nucleosides and their Conformational Analysis by 500 MHz 1H NMR Spectroscopy

Tong, W.; Agback, Peter; Chattopadhyaya, J.


Electrophilic addition reactions of alcohols to 4',5'-unsaturated nucleosides 1 and 2 under mild, acidic conditions have produced various diastereomerically pure 4'-alkoxy-beta(D)- and 4'-alkoxy-alpha(L)-5'-deoxy-nucleosides 3-11 in good yields. The steric hindrance exerted by the bulk of the alcohol was the principal factor governing the distribution of diastereomers in the reactions of 1. The distribution was, however, reversed when 2 was used as the substrate. The synthesis of various 4'-alkoxy-4'-hydroxymethyl-beta(D)-/alpha(L)-nucleosides 12-15 has been achieved by the action of m-chloroperbenzoic acid and an alcohol on 1 and 2. This reaction followed a reaction sequence involving the oxidation of the double bond followed by the alcohol-promoted ring-opening of the epoxide ('oxidation substitution'). This oxidation-substitution reaction did not show the same striking diastereoselectivity owing to the fact that the proportion of the final products was dictated at the first radical-oxidation step, which showed almost equal diastereofaciality. The configuration at C4' was assigned with the help of 1D differential NOE experiments at 500 MHz at 20-degrees-C. Clear NOEs between H3' and 4'-methyl and between H6 and 4'-methyl were observed for 3b, 4b, 6b and 7b suggesting a beta(D) configuration for the methyl at C-4'. The absence of these NOEs in 3a, 4a, 5, 6a and 7a allowed us to assign the C-4' substituent in the alpha(L) configuration. Observed ID differential NOEs between H6 and H5'/5'' and between H3' and H5'/5'' in 13b, 14b and 15b suggested that the 4'-alkoxy groups are in the alpha(L) configuration. Absence of these NOEs in compounds 13a, 14a and 15a suggested that the 4'-alkoxy groups are in the beta(D) configuration. Thee 4'-alkoxy substituted ribose rings in compounds 3a, 4a, 5, 6a are biased to a South-type conformation in the N reversible S equilibrium (>ca. 90%) (PHI(m) for 3a, 4a, 5, 6a almost-equal-to 42-degrees, P(S) are around 160-170-degrees), and the 4'-triazolo-substituted compound 7b also seems to adopt a modified South-type conformation (>ca. 80 %) (PHI(m) is < 35-degrees, P(S) almost-equal-to 180-degrees). The pseudorotamer population of the constituent sugar in the N reversible S equilibrium in compounds 13a, 14a and 15a is biased to the S conformer (ca. 80 %) with PHI(m) almost-equal-to 42-degrees and P(S) of around 160-170-degrees. All 4'-alkoxynucleosides reported herein have been found to have an anti conformation across their glycosidic bonds.

Published in

1993, Volume: 47, number: 2, pages: 156145

    UKÄ Subject classification

    Organic Chemistry

    Publication Identifiers


    Permanent link to this page (URI)