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Abstract

A systematic search for the conditions required to effect a transglycosidation reaction between 2'-substituted-2'-deoxyuridine nucleosides and adenine has been undertaken. Evidence for transglycosidation having taken place, albeit to an extremely limited extent, is presented. The conditions needed to allow more efficient transglycosidation reactions to occur have been more clearly defined.

2'-Chloro, 2'-bromo, 2'-iodo and 2'-azido-2'-deoxyuridine have been prepared via the ring opening of 0? »2'-cyclouridine derivatives with the appropriate nucleophile. Treatment of the above 2'-substituted-2'- deoxyuridine nucleosides with acetic anhydride in pyridine has afforded the 3',5'-di-O-acetyl analogues. 3',5'-di-O-acetyl-2'-chloro- and -2'- bromo- 2 -deoxyuridine have been successfully converted to their corresponding N3-benzoyl analogues by reaction with benzoyl chloride in pyridine. The 5'-O0-trityl analogues of 2'-chloro, 2'-bromo and 2'-azido-2'- deoxyuridine have been prepared by several methods, the products and reaction conditions having been more fully characterised than previously. Treatment of the above 5'-O-trityl derivatives with 3-benzoylpropionic acid and dicyclohexylcarbodiimide in pyridine has afforded the 3'-0-(3-benzoylpropionyl) analogues. The action of nitronium tetrafluoroborate on 3',5'-di-O-acety1-2'-substituted-2'-deoxyuridine nucleosides has been found to afford the corresponding 5-nitro compounds in reasonable yields and some evidence for a limited amount of glycosidic bond cleavage during the reaction was also found.

Attempted transglycosidation reactions involving n>-benzoy lated uridine derivatives resulted in transbenzoylation from the pyrimidine to the purine base, causing delabilisation of the glycosidic bond, which resulted in transglycosidation only being exhibited in one isolated experiment, the reaction yielding only traces of the required product. Attempted transglycosidation reactions involving 3'-0-(3-benzoylpropionyl) uridine derivatives resulted in a similar transacylation of the (3-benzoylpropionyl) group from the pyrimidine nucleoside to the purine base. Attempted transglycosidation reactions using 5-nitro-2'-halogeno-2'-deoxyuridine derivatives did not result in glycosyl-transfer to the purine base and reactions using a derivative of N3-methyl-2'-iodo-2'-deoxyuridine resulted in loss of hydrogen iodide from the starting material.

The synthesis of 2'-azido-thymidine is described, starting from D-ribose and thymine. The use of lithium azide has been found to result in some glycosidic bond cleavage, but, the use of tetramethylguanidinium azide as a source of azide ion resulted in a milder and cleaner azidolysis reaction.

A systematic survey of the 13C n.m.r. spectra of the majority of the compounds prepared has shown this spectroscopic technique to be an invaluable tool in this field of research, and its use has allowed the characterisation of unknown compounds. The effect of electron-withdrawing substituents on the heterocyclic ring has resulted in a small, but characteristic, downfield chemical-shift at C-1' being observed, Similarly, the modification of C-2' by various substituents has resulted in chemical shift values for C-2' that are characteristic of the substituent at this position.

Publication Type:	Thesis (Doctoral)
Subjects:	Q Science Q Science > QD Chemistry
Departments:	School of Science & Technology > School of Science & Technology Doctoral Theses Doctoral Theses

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