Chemical studies of 8-substituted pteridines

Rowan, Thomas (1964) Chemical studies of 8-substituted pteridines. PhD thesis, University of Glasgow.

Abstract

An account is given of the methods which are at present available for the aynthesis of 8-substituted pteridines and the closely allied 9-substituted isoalloxazine derivatives. The theories reported in the literature relating to the biosynthesis of riboflavin, which may be considered to be a senzopteridine with a substituent in the 8-postion of the pteridine moiety, are reviewed. The chamical festibility of the biosynthetic routes to riboflavin, which have been suggested in the literature, is investigated. It is found that 6,7-dimethyl-8-d-ribityllumazine ("G-compound"), which is an intermediate in the biosynthesis of the vitamin, can be readily converted chemically into 7,8-dihydro-2,6-dihydroxy-6-methyl-7-oxo-8-d-ribitylpteridine (V-compound"), whichi is a known by -product in the biosynthetic process. This conversion is shown to occur by oxidation or, in an inert atmosphere, by displacement of the diacetyl residue of the lumazine derivative by pyruvsats. The hydration in alkaline solution of 8-substituted "quinonoid" pteridines, such as "G-compound", is described and the significance of this in relation to the biosynthetic pathway leading to riboflavin and to the biological converstion of "G"-compound" into "v-compound", is discussed. A new synthesis of riboflavin from "G-compound" is reported, the salient feature being its simplicity. Thus, when the lumazine is refluxed in a buffer solution of ph 7.3, in the absence of any enzyme or other source of carbon, riboflavin is produced in good yield. This resction is suggested. Attempts to synthesise pteridine-8-glycosides analogous to the purins nucleosides are described, the two main spporoaches to this problem being (a) direct alkylation of pteridines and (b) anythesis from 4.5-diaminopyrimidine precursors. Model reactions with 5-amino-4-alkylaminopyrimidines are reported in which 8-alkly-pteridines are readily formed by the well-known "Isay reaction". It is found, however, that when the corresponding 5-amino-4-glucosylaminopyrimidine is reacted with dicarbonyl compounds such as diacetyl or glyoxal, surprisingly only the intermediate Schiff base, which cannot be cyclized to the expected pteridine -8- glucoside, is formed. This is in contract to the reaction of the pyrimidine glucoside with ethyl pyruvate or with ethyl glyoxylate hemiacetal which readily gives the appropriate 7-oxo-pteridine-8-glucoside. Other attempts to synthesise these elusive glycosides are doscribed in detail.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: H CS Wood
• Keywords: Organic chemistry
• Date of Award: 1964
• Depositing User: Enlighten Team
• Unique ID: glathesis:1964-73765
• 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/73765