Nucleic acid related compounds. 81. Syntheses of 9‐(3‐deoxy‐β‐D‐threo‐pentofuranosyl)adenine, the core nucleoside of the extraordinarily selective antibiotic agrocin 84, and simplified structural component analogues

Abstract

AbstractAlternative syntheses of 9‐(3‐deoxy‐β‐D‐threo‐pentofuranosyl)adenine (4), the core nucleoside of agrocin 84 [and its 2′‐deoxy threo isomer 5] were devised: (1) direct conversion of 9‐(β‐D‐arabinofuranosyl)adenine into 9‐(2,3‐anhydro‐β‐D‐lyxofuranosyl)adenine and regioselective opening of its oxirane ring with sodium borohy‐dride to give 4 and 5(˜7.5:1); (2) treatment of adenosine with sodium hydride and 2,4,6‐triisopropylbenzene‐sulfonyl chloride, and subjection of the resulting 2′(3′)‐sulfonates to the reductive [1,2]‐hydride shift rearrangement with lithium triethylborohydride to give 4 and 5 (˜ 2:1); and (3) subjection of the phenoxythiocar‐bonyl esters of 9‐[2(3),5‐bis‐O‐(tert‐butyldimethylsilyl)‐β‐D‐arabinofuranosyl]adenine to Barton deoxygenation, and deprotection to give 4 and 2′‐deoxyadenosine (˜5:1). Methods (2) and (3) gave lower yields. Syntheses of simplified 6‐N‐ and 5′‐O‐adenosine phosphoramidate model compounds were explored to examine potential access to such features in the structure proposed for agrocin 84.