University of Illinois Urbana-Champaign

Synthesis and Structure Assignments of Novel Azolinone Ribonucleosides

Haines, David Richard

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Description

Title
Synthesis and Structure Assignments of Novel Azolinone Ribonucleosides
Author(s)
Haines, David Richard
Issue Date
1981
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Chemistry, Organic
Language
eng
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.
Graduation Semester
1981
Type of Resource
text
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