| Abstract: |
As an epimerization resistant synthon in the synthesis of oligonucleotides consisting of C-nucleoside analogues, hitherto unknown 5-benzyloxymethyl-3-(2-deoxy-β-D-erythro-pentofuranosyl)pyrrolo[3, 2-d]pyrimidine (7-benzyloxymethyl-2’-deoxy-9-deazaadenosine) was prepared in seven steps from the known 3-amino-2-cyano-4-(2, 3-O-isopropylidene-5-O-trityl-β-D-ribofuranosyl)-pyrrole (1). Treatment of 1 with benzyl chloromethyl ether in the presence of potassium t-butoxide and 18-crown-6 afforded the N-protected pyrrole 2, which was converted into the 9-deazapurine derivative 3 in high yield by heating in EtOH. 7-Benzyloxymethyl-9-deazaadenosine 4 was obtained from 3 by acid hydrolysis in 2.5% methanolic hydrogen chloride. After protection of the hydroxyl groups of 4 with Markievicz’s reagent, the product 5 was converted into the 2-O-phenoxythiocarbonyl derivative 6. Reduction of 6 with butyltin hydride in the presence of 2, 2’-azobis(2-methylpropionitrile), followed by desilylation with triethylammonium fluoride, afforded the desired 7-benzyloxymethyl-2’-deoxy-9-deazaadenosine (8) in high overall yield. The benzyloxymethyl group of 8 was removed by hydrogenolysis over palladium hydroxide (Degussa type) to give 2’-deoxy-9-deazaadenosine (9) in quantitative yield. The structure of 9 is discussed. © 1993, Taylor & Francis Group, LLC. All rights reserved. |
