Stereoselective Synthesis of Indazole 2′‐Deoxy‐β‐<scp>D</scp>‐ribonucleosides: Glycosylation of the Nucleobase Anion

Abstract

Abstract The glycosylation of indazolyl anions derived from 4a , b with 2‐deoxy‐3,5‐bis‐ O ‐(4‐methylbenzoyl)‐α‐ D ‐ erythro ‐pentofuranosyl chloride ( 5 ) is described. The reaction was Stereoselective – exclusive β‐ D ‐anomer formation – but regioisomeric N 1 ‐ and N 2 ‐(2′‐deoxy‐β‐ D ‐ribofuranosides) ( i.e. 6a and 7a , resp., and 6b and 7b , resp.) were formed in about equal amounts. They were deprotected to yield 8a , b and 9a , b . Compound 1 , related to 2′‐deoxyadenosine ( 3 ), and its regioisomer 2 were obtained from 8b and 9b , respectively, by catalytic hydrogenation. The anomeric configuration as well as the position of glycosylation were determined by 1D NOE‐difference spectroscopy. The first protonation site of 1 and 2 was found to be the NH 2 group. The N ‐glycosylic bond of 1 H ‐indazole N 1 ‐(2′‐deoxyribofuranosides) is more stable than that of the parent purine nucleosides. Compound 1 is no substrate for adenosine deaminase.