Synthesis and Adenosine Deaminase Inhibitory Activity of 3′-Deoxy-1-deazaadenosines

Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases

“…Substitution in the N6 position of 2′-deoxyribose derivatives with hydroxyl, methyl and cyclopropyl groups resulted in good inhibitory effects with Ki values 0.25, 1.2 and 5.9 µM, respectively [ 59 ]. 3′-Deoxy-1-deazaadenosine and 2′3′-dideoxy-1-deazaadenosine also presented good inhibitory activities for ADA and there were as follows, Ki = 2.6 µM and Ki = 2.2 µM [ 60 ]. Interestingly, even though 3-deazaadenosine did not show a significant inhibitory properties for ADA, it has been described as a potent inhibitor and substrate for intracellular enzyme, S -adenosylhomocysteine hydrolase (SAHH) [ 85 ].…”

Adenosine deaminase: Functional implications and different classes of inhibitors

“…70,209 Moreover, the presence in these series of a chlorine atom in position 2 produced a decrease in ADA inhibitory activity. 38 A series of 3 H -deoxy-1-deazaAdos 211 and 2 H ,3 H -dideoxy-1-deazaAdos 209 has been also synthesized and evaluated as inhibitors of ADA from calf intestine. 210 Substitution in the N 6 -position of such 1-deaza derivatives was also performed and the resulting nucleosides were tested on ADA.…”

Stereocontrolled Syntheses of Deoxyribonucleosides via Photoinduced Electron-Transfer Deoxygenation of Benzoyl-Protected Ribo- and Arabinonucleosides

“…3 ‘ -Deoxycytidine (54c). Obtained in 80% yield as a white powder: mp 217−219 °C (lit 31a. mp 220 °C); [α] 23 D +50° ( c 0.8, H 2 O); IR (KBr) 1649, 1605, 1529, 1492, 1403, 1288 cm -1 ; 1 H NMR (D 2 O) δ 7.83 (d, J = 7.5, 1H), 5.93 (d, J = 7.5, 1H), 5.75 (s, 1H), 4.51−4.43 (m, 1H), 4.40−4.37 (m, 1H), 3.90 (dd, J = 12.7, 2.8, 1H), 3.71 (dd, J = 12.7, 5.0, 1H), 1.95−1.90 (m, 2H); 13 C NMR δ 166.5, 157.8, 141.5, 95.8, 93.3, 81.9, 76.0, 62.4, 32.8.…”

“…Much of the interest in this class of compounds has centered on cordycepin (3‘-deoxyadenosine), which was the first reported nucleoside antibiotic . More recently, 3‘-deoxynucleosides were shown to possess antiviral, antifungal and antitumor activities as well . Oligomers of 3‘-deoxynucleosides possessing the unnatural 2‘,5‘-phosphodiester linkage have also attracted some interest. , …”

“…Stereocontrolled syntheses of 3‘-deoxynucleosides have been previously reported from the glycosylation of 41 (Scheme ). In this work, 41 was prepared from commercially available 1,2- O -isopropylidene- d -xylose by selective benzoylation of the C5-hydroxyl followed by Barton deoxygenation of the C3-position to give 40 . 31a,f,32b We have previously shown that 40 , the immediate precursor to 41 , can be conveniently prepared by benzoylation of 1,2- O -isopropylidene- d -xylose to give 39 , followed by PET deoxygenation 10b. Given some of the difficulties we experienced in the deoxygenation of 37 such as long reactions times and unwanted side reactions, the synthesis of β-3‘-deoxynucleosides from 41 (Scheme ) may be superior in some cases.…”