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Development of selective agonists of adenosine receptors optimization of the synthetic procedures to obtain 2-chloropurine and analogues
Mimochodková, Lenka ; Vinšová, Jarmila (advisor) ; Špulák, Marcel (referee)
CONCLUSION This thesis describes the synthesis of nucleosides and their analogues that are of enormous importance. They are an established class of clinically useful medicinal agents, possessing antiviral and anticancer activity. From a chemical point of view, in this work, we focus on the synthesis of adenosine and nucleoside analogues. In the adenosine nucleoside series the purine base was altered at the 2- and N6-position. In the method developed by Vorbrüggen, the glycosidic bond formation is driven by the use of 2,6- dichlorpurine and 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose in combination with strong Lewis acids, like trimethylsilyl trifluoromethanesulfonate and a base diazabicyclo [5.4.0]undec-7- ene. This Vorbrüggen coupling reaction is the reference in nucleoside synthesis and provides a highly reproducible method for 2,6-dichloro-9H-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)purine formation in high yield (86 %) with reliable and predictable stereochemistry, i.e. orientation of the glycosidic bond. Displacement of the 6-chloro atom in 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose with ammonia or isobutylamine, followed by deprotection, produced the 2-chloroadenosine and the 2- chloro-N6-isobutyladenosine. 2-Chloroadenosine and 2-chloro-N6-isobutyladenosine are used as a starting material for...
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Development of selective agonists of adenosine receptors optimization of the synthetic procedures to obtain 2-chloropurine and analogues
Mimochodková, Lenka ; Vinšová, Jarmila (advisor) ; Špulák, Marcel (referee)
CONCLUSION This thesis describes the synthesis of nucleosides and their analogues that are of enormous importance. They are an established class of clinically useful medicinal agents, possessing antiviral and anticancer activity. From a chemical point of view, in this work, we focus on the synthesis of adenosine and nucleoside analogues. In the adenosine nucleoside series the purine base was altered at the 2- and N6-position. In the method developed by Vorbrüggen, the glycosidic bond formation is driven by the use of 2,6- dichlorpurine and 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose in combination with strong Lewis acids, like trimethylsilyl trifluoromethanesulfonate and a base diazabicyclo [5.4.0]undec-7- ene. This Vorbrüggen coupling reaction is the reference in nucleoside synthesis and provides a highly reproducible method for 2,6-dichloro-9H-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)purine formation in high yield (86 %) with reliable and predictable stereochemistry, i.e. orientation of the glycosidic bond. Displacement of the 6-chloro atom in 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose with ammonia or isobutylamine, followed by deprotection, produced the 2-chloroadenosine and the 2- chloro-N6-isobutyladenosine. 2-Chloroadenosine and 2-chloro-N6-isobutyladenosine are used as a starting material for...
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