Modified Purines. Rearrangement Through 5-Substituted Purine Intermediates

A novel rearrangement has been utilized for the synthesis of imidazo{1,5-a}-1,3,5-triazinones (1) which are analogues of N(9)-substituted guanines, hypoxanthines, and xanthines. Structures were established in this series (1) on the basis of precursors and routes of synthesis, infrared spectra, mass spectra, ('1)H and ('13)C nuclear magnetic resonance spectra, and X-ray crystallographic analysis of one member among the interrelated compounds in the series. Condensation of various (alpha)-cyanoesters with urea, thiourea, guanidine, and N('1),N('1)-dimethylguanidine yielded substituted 4,5-dihydropyrimidin-4-ones (2). Treatment of the 4,5-dihydropyrimidin-4-ones 2 with chlorotrimethylsilane and hexamethyldisilazane in pyridine gave the correspondingly substituted imidazo{1,5-a}-1,3,5-triazinones 1. The syntheses of compounds of type 1 by cyclization-rearrangement of the monocyclic derivatives 2 indicated the generality of this synthetic approach to imidazo{1,5-a}-1,3,5-triazines with variation in substitution at C(2), C(5), and the C(5)-amide group of the 4,5-dihydropyrimidin-4-one precursors 2 (see numbering system in 2). The possibility of successful preparation of imidazo{1,5-a}-1,3,5-triazine products with variation in substitution at C(5) is of particular interest in view of (a) the analogy between C(8) substitution in the imidazo{1,5-a}-1,3,5-triazines 1 and N(9) substitution on guanine, hypoxanthine, and xanthine; and (b) since substitution at C(5) of the monocyclic heterocycle results in substitution on C(8) in the corresponding imidazo{1,5-a}-1,3,5-triazine. Incorporation of a ribosyl unit or analogous moiety at the C(5) position of the monocyclic heterocycle could give, after cyclization-rearrangement, imidazo{1,5-a}-1,3,5-triazine analogues of naturally occurring nucleic acid bases. Additional modifications could then provide analogues of naturally occurring nucleosides, nucleotides, and coenzymes.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2014

Author dc:creator

• Holtwick, Joseph Bernard

• Chemistry, Organic

Language dc:language

eng

Identifier

(UMI)AAI8127610

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/67278