TY - JOUR
T1 - Synthesis of Carbocyclic Aminonucleosides
AU - Daluge, Susan
AU - Vince, Robert
PY - 1978
Y1 - 1978
N2 - 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.
AB - 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.
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U2 - 10.1021/jo00406a002
DO - 10.1021/jo00406a002
M3 - Article
AN - SCOPUS:0017803457
SN - 0022-3263
VL - 43
SP - 2311
EP - 2320
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 12
ER -