| Abstract: | "In the first part of this thesis, we describe the enantioselective synthesis of an analogue of sinefungin in which adenosine is replaced by thymidine. The essential carbon skeleton of sinethymidin was constructed by two radical reactions: the first one is the addition of a radical, generated by photolysis of N-hydroxy-2 thiopyridone ester of the protected thymidine 5' carboxylic acid to the allylic amide according to a SH2' reaction. The resulted olefin intermediate undergoes a second addition reaction with the radical derived by irradiation of the N-hydroxy-2-thipyridone ester of L-aspartic acid to furnish the target protected sinethymidin. In order to increase the overall yield of sinethymidin, we examined a new method for the preparation of N-hydroxy-2-thiopyridone esters. this new approach, reported recently by Baron and Samadi, proceeds very smoothly and uses 2,2'-dithiopyridone-1,1'-di-N-oxide and tributyl or triphenyl phosphine. We also experienced and found new conditions for the Hofmann rearrangement. The new procedure allows in one step the transformation of an amide group into the corresponding t-butyl-carbamate. The sinethymidin was tested for their antileismanial effect. This analogues was devoid of any anti-parasitic activity. This result shows the important role of adenine in the biological activity. In the second part, we reported a convenient synthesis of C-cyclopurine and C-cyclodihydropyrimidine nucleosides using 5'-anisyl-telluronucleosides. Generation of methyl radicals from photolysis of acetyl derivative of N-hydroxy-2-thiopyridone permitted by radical exchange, the formation of 5' nucleoside racial which was added to the purine or pyrimidine by intramolecular fashion to yield the cyclonucleosides in a satisfactory yield." |
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