169221-19-6Relevant articles and documents
Efficient and β-stereoselective synthesis of 4(5)-(β-D-ribofuranosyl)- and 4(5)-(2-deoxyribofuranosyl)imidazoles
Harusawa, Shinya,Murai, Yoshihiko,Moriyama, Hideki,Imazu, Tomonari,Ohishi, Hirofumi,Yoneda, Ryuji,Kurihara, Takushi
, p. 4405 - 4411 (2007/10/03)
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 7RS. Hydrolysis of 7RS gave a 1:1 mixture of diol isomers 8R and 8S having an unsubstituted imidazole. Mitsunobu cyclization of the mixture 8RS 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 14RS 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.
