Synthesis of Carbocyclic Aminonucleosides

Susan Daluge, Robert Vince

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126 Scopus citations

Abstract

The syntheses of the racemic carbocyclic analogues of puromycin aminonucleoside (33), 3'-amino-3'deoxyade-nosine (26), and 3'-amino-3'-deoxyarabinosyladenine (21) are described. Acidic hydrolysis of 2-azabicyclo[2.2.1]-hept-5-en-3-one (1), followed by esterification and acetylation, gave methyl cis-4-acetamidocyclopent-2-enecarboxylate (2a). Reduction of 2a with calcium borohydride gave, after acetylation, cis-4-acetamidocyclopent-2-ene-methyl acetate (3b). Epoxidation of 3b gave only cis-epoxide 6b, which was opened with sodium azide to give, after acetylation, 4α-acetamido-3α-acetoxy-2β-azido-1α-cyclopentanemethyl acetate (7a) as the major regioisomer. Catalytic hydrogenation of 7a, followed by immediate acetylation, gave 3α-acetoxy-2β,4α-diacetamido-1α-cyclopentanemethyl acetate (9a). Selective hydrolysis of the 4-acetamido group of 9a and formation of the purine moiety at this position, followed by hydrolysis of the remaining acetamido group, gave the arabino analogue 21. Epimerization at C-2' gave access to ribo analogues 33 and 26. Preliminary in vitro screening data indicate that carbocyclic 3'-amino-3'-deoxyadenosine exhibits highly significant antiviral activity.

Original languageEnglish (US)
Pages (from-to)2311-2320
Number of pages10
JournalJournal of Organic Chemistry
Volume43
Issue number12
DOIs
StatePublished - Jan 1 1978

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