Efficient and β-Stereoselective Synthesis of 4(5)-(β-d-Ribofuranosyl)- and 4(5)-(2-Deoxyribofuranosyl)imidazoles1

• Published in: Journal of organic chemistry Vol. 61; no. 13; pp. 4405 - 4411
• Main Authors: Harusawa, Shinya, Murai, Yoshihiko, Moriyama, Hideki, Imazu, Tomonari, Ohishi, Hirofumi, Yoneda, Ryuji, Kurihara, Takushi
• Format: Journal Article
• Language: English
• Published: American Chemical Society 26.06.1996
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo952136z

A synthetic route to 4(5)-(β-d-ribofuranosyl)imidazole (1), starting from 2,3,5-tri-O-benzyl-d-ribose (5), was developed via a Mitsunobu cyclization. Reaction of 5 with the lithium salt of bis-protected imidazole afforded the corresponding 5-ribosylimidazole 7 RS . Hydrolysis of 7 RS gave a 1:1 mixture of diol isomers 8 R and 8 S having an unsubstituted imidazole. Mitsunobu cyclization of the mixture 8 RS using N,N,N‘,N‘-tetramethylazodicarboxamide and Bu3P exclusively afforded benzylated β-ribofuranosyl imidazole 9β in 92% yield, accompanied by α-anomer 9α, in a ratio of 26.3:1. The configuration of 9β was established by X-ray crystallography of ethoxycarbonyl derivative 10β. Reductive debenzylation of 9β over Pd/C was carried out, and the synthesis of 1 was attained from starting 5 in four steps and 87% overall yield. This synthetic methodology was extended to the synthesis of 4(5)-(2-deoxy-β-d-ribofuranosyl)imidazole (2). Mitsunobu cyclization of a 1:1 mixture of the corresponding diol isomers 14 RS produced 15β and 15α in a ratio of 5.4:1. The synthesis of 2 was attained in a 59% overall yield from the starting 3,5-di-O-benzyl-2-deoxy-d-ribose (12). β-Stereoselective glycosylation in the key step is discussed and explained by intramolecular hydrogen bonding between an NH in the imidazole and the oxygen functional group in the sugar moiety.