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|Title:||Synthesis and Structure Assignments of Novel Azolinone Ribonucleosides|
|Author(s):||Haines, David Richard|
|Department / Program:||Chemistry|
|Degree Granting Institution:||University of Illinois at Urbana-Champaign|
|Abstract:||Ribosidation of a series of azolinones was achieved via silylation and SnCl(,4) catalysis. Ribosidation of 4-imidazolin-2-one gave 1-(beta)-D-ribofuranosyl-4-imidazolin-2-one; of 1,2,4-triazolin-3-one gave 1-, 2-, and 4-(beta)-D-ribofuranosyl-1,2,4-triazolin-3-one, and 2,4-bis-(beta)-D-ribofuranosyl-1,2,4-triazolin-3-one; and of 2-tetrazolin-5-one gave 1-(beta)-D-ribofuranosyl-2-tetrazolin-5-one and 1,4-bis-(beta)-D-ribofuranosyl-2-tetrazolin-5-one. Structure assignments were based on microanalyses and ('1)H and ('13)C NMR spectra. The triazolinone mono-riboside isomer structures are differentiated by ('13)C NMR long-range coupling patterns, and two of the assignments were confirmed by X-ray crystallography. Improved syntheses were developed for two of the ribosides by fashioning the azolinone rings onto 2,3,5-tri-O-benzoylribofuranosyl isocyanate. Reaction of 2,3,5-tri-O-benzoylribofuranosyl isocyanate with (alpha)-aminoacetaldehyde diethyl acetal gave N-(2,2-diethoxyethyl)-N'-(beta)-D-(2,3,5-tri-O-benzoylribofuranosyl)-4-imidazolin-2-one in the presence of acid. Addition of formic acid hydrazide to 2,3,5-tri-O-benzoylribofuranosyl isocyanate gave 1-formyl-4-(beta)-D-(2,3,5-tri-O-benzoyl-ribofuranosyl)semicarbazide, which gave 4-(beta)-D-(2,3,5-tri-O-benzoylribofuranosyl)-1,2,4-triazolin-3-one upon dehydrative silylation. Methyl N-carbomethoxyformimidate was synthesized as a possible reagent for the synthesis of the other 1,2,4-triazolin-3-one products.
Carbamoylation of 4-imidazolin-2-one, 1,2,4-triazolin-3-one, and 2-tetrazolin-5-one was achieved using either trimethylsilyl isocyanate or phosgene and ammonia, giving 1-carbamoyl-4-imidazolin-2-one, 2- and 4-carbamoyl-1,2,4-triazolin-3-one, and 1-carbamoyl-2-tetrazolin-5-one, respectively. Protection of nucleosides with t-butyldimethylsilyl chloride permitted carbamoylation on the heterocyclic base using trimethylsilyl isocyanate. Protection of inosine gave 2',3',5'-tri-O-t-butyldimethylsilylinosine, which was carbamoylated to give 1-carbamoyl-2',3',5'-tri-O-t-butyldimethylsilylinosine.
Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1981.
|Date Available in IDEALS:||2014-12-13|