Synthesis of 2′-deoxy-β-d-ribofuranosyl imidazole and thiazole C-nucleosides

Donald E. Bergstrom, Peiming Zhang, Jie Zhou

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Abstract

A synthetic route to 2-carbamoyl-4-(2′-deoxy-β-D-ribofuranosyl) imidazole 3, starting from 2-deoxy-3,5-di-O-toluoyl-β-D-ribofuranosyl cyanide 4. was developed. The key steps are reduction of the cyano group of compound 4 to a formyl and subsequent condensation with tosylmethyl isocyanide to yield the formamido derivative 7, which was dehydrated to an isocyanide and ring closed with either ammonia or a primary amine to yield protected C-4 linked imidazolyl deoxyribosyl derivatives 9a-c. Ring closure with H2S followed by removal of the toluoyl protecting groups with ammonia gave 5-(2′-deoxy-β-D-ribofuranosyl)thiazole 11. A cyano group can be introduced at C-2 of the imidazole nucleosides by way of the reagent N-cyano-4-(dimethylamino)pyridinium bromide. Subsequent hydrolysis of the cyano functional group with alkaline hydrogen peroxide yields a carboxamide substituent. All of the transformations were able to be carried out without affecting the β-configuration at the anomeric carbon. A p-nitrophenylethyl protecting group was introduced at N-3 of the imidazole during ring closure in order to obtain a protected derivative that could be selectively modified at the deoxyribosyl (eryrtro-pentofuranosyl) hydroxy groups.

Original languageEnglish (US)
Pages (from-to)3029-3034
Number of pages6
JournalJournal of the Chemical Society, Perkin Transactions
Issue number20
StatePublished - Dec 1 1994

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ASJC Scopus subject areas

  • Chemistry(all)

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