The biosynthesis of riboflavin and related pteridines

Neilson, Thomas (1961) The biosynthesis of riboflavin and related pteridines. PhD thesis, University of Glasgow.

Abstract

The evidence in the literature relating to the biosynthesis of riboflavin and of other simpler pteridines is reviewed. Possible intermediates in the transformation of purines into pteridines are discussed and the chemistry of some of these compounds has been investigated. The key intermediate appears to be 1-[2',6'-dihydroxy-5'-nitro-4'-pyrimidinylamino]-l-deoxy-D-erythropentulose which could be formed by Amadori rearrangement of a substituted diaminopyrimidine glycosideo. This intermediate has been synthesised by the condensation of 4-chloro-2,6-dihydroxy-5-nitropyrimidine with l-amino-l-deoxy-D-erythropentulose. Stereospecific reduction of the carbonyl group in the side-chain of this pyrimidine was achieved giving 2,6-dihydroxy-5-nitro-4-D- ribitylaminopyrimidline which on subsequent reduction of the 5-nitro group and condensation with the dimer of 3,4-dimethyl-o-benzoquinone gave riboflavin. Proof of the stereospecific reduction was supplied by unambiguous synthesis of both pyrimidine isomers. Model experiments using 1-[2',6'-dihydrozy-5'-nitro-4'-pyrimidinylamino]-1-deoxy-D-fructose are also described. The implications of these reactions in the biosynthesis and synthesis of riboflavin are discussed. Oxidative self-condensation and condensation with alloxan of 5-amino-2,6-dihydroxy-4-substituted aminopyrimidines gave 2,10-dihydro-2-oxo-10-substituted-4,6,8-trihydroxypyrimido[5,4-g] pteridines. The conversion of the key intermediate, 1-[2',6'-dihydroxy-5'-nitro-4'-pyrimidinylamino]-1-deoxy-D-erythropentulose to simple pteridines was also investigated. Thus, reduction of the 5-nitro group of the model, 1-[2',6'-dihydroxy-5'-nitro-4'-pyrimidinylamino]-1-deoxy-D-fructose, and intramolecular condensation followed by oxidation of the resulting dihydropteridine, gave the 2-hydroxy analogue of xanthopterin and not the expected 6-polyhydroxyaIkylpteridine. Model experiments using 4-acetonyl-amino-2,6-dihydroxy-5-nitropyrimidine are also described. The hydrazine derivative of this model pyrimidine gave 2,4-dihydroxy-6-methylpteridine directly, but attempts to apply this technique to sugar containing pyrimidine were not successful. 4-Acetonylamino-2,6-dihydroxy-5-nitropyrimidine and 2,6-dihydroxy-4-2'-hydroxyethylamino-5-nitropyrimidine underwent an unusual intramolecular condensation to give imidazo[1,2-c] pyrimidine derivatives. Alkylation of guanosine using bensyl bromide, gave a crystalline quaternary salt which on subsequent treatment with dilute alkali underwent cleavage of the imidazole ring to give a 5-amino-4-D-ribosylaminopyrimidine derivative. An attempt to synthesise this glycoside directly proved unsuccessful as the product was suspected of undergoing an Amadori rearrangement.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: H CS Wood
• Keywords: Organic chemistry
• Date of Award: 1961
• Depositing User: Enlighten Team
• Unique ID: glathesis:1961-73585
• 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/73585