Addition reactions of 7,8-dihydropteridines and the biosynthesis of xanthopterin

Stuart, Alexander (1962) Addition reactions of 7,8-dihydropteridines and the biosynthesis of xanthopterin. PhD thesis, University of Glasgow.

Abstract

The addition reactions undergone by double bonds in certain heterocyclic compounds are reviewed. The formation of 2,6-diaraino-4-hydroxypteridine by reoxidation of 2-amino-4-hydroxy-5,6,7,8-tetrahydropteridine in the presence of ammonia is discussed with reference to two possible dihydropteridine intermediates. These intermediates could be considered to be sufficiently reactive to add ammonia followed by oxidation of the addition product to give 2,6-diamino-4-hydroxypteridine. The unambiguous synthesis of one of these dihydropteridines, 2-amino-4-hydroxy-7,8-dihydropteridine, is outlined and its reaction with ammonia has been investigated. This revealed the ready addition of ammonia to give a tetrahydropteridine derivative which on oxidation gave 2, 6-diamino-4-hydroxypteridine, thus confirming the above theory. The structure of this compound was confirmed by an unambiguous synthesis. This led to a new synthesis of 7,8-dihydroxanthopterin which involved an interesting modification of existing methods. Spectral studies of the didydropteridines and their oxidation products, together with comparisons with related pyrimidines, gave rise to a relationship between the structure of a dihydropteridine and its ultraviolet spectra. The addition reactions undergone by 2-amino-4-hydroxy-7,8-dihydropteridine and a number of simple reagents have been investigated, and are found to give rise to a variety of 6-substituted pteridines. The addition of hydrogen cyanide gave a tetrahydropteridine derivative which, on oxidation, gave a dihydropteridine whose ultraviolet spectra indicated the possible existence of a new chromophore is pteridine chemistry. Oxidation of this compound gave 2-amino-4-hydroxypteridine-6-carboxylic acid. The addition of hydrogen sulphite led to the formation of 2-amino-4-hydroxypteridine-6-sulphonic acid. The addition of Michael-type reagents proceeded smoothly to give tetrahydropteridine derivatives which, on oxidation, gave 2-amino-4-hydroxypteridine-6-carboxylic acid. Thiols were found to add particularly easily to give tetrahydropteridines. Alkali added only with difficulty giving xanthopterin after oxidation. Current theories of the biosynthesis of xanthopterin have suggested that 1-[2',5'-diamino-6'-hydroxy-4'-pyrimidinyl-amino]-1-deoxy-D-erythropentulose is a key intermediate. This material has been synthesised and its conversion via 7,8-dihydro-xanthopterin to xanthopterin has been achieved, thus furnishing chemical support for the above theories.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: H CS Wood
• Keywords: Organic chemistry
• Date of Award: 1962
• Depositing User: Enlighten Team
• Unique ID: glathesis:1962-73763
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jun 2019 08:56
• Last Modified: 14 Jun 2019 08:56
• URI: https://theses.gla.ac.uk/id/eprint/73763