Syntheses of two series of 2'-sugar-modified pyrimido[4,5-b]indole nucleosides were developed. The synthetic strategy was based on functional group transformations of the 2'-hydroxy group of the 3',5'-protected ribonucleoside. The key intermediate was prepared via stereoselective nucleobase anion glycosylation of the known 4,6-dichloropyrimido[4,5-b]indole nucleobase with 2,3-O-isopropylidene- 5-O-TBS-protected halogenose, subsequent deprotection under acidic conditions and protection of 3'- and 5'-hydroxy groups with Markiewicz reagent. Pyrimidoindole arabinonucleoside was then synthesized using a sequence of oxidation-reduction reactions of the 2'-hydroxy stereocenter. The synthesis of pyrimidoindole 2'-deoxy- 2'-fluororibonucleoside was achieved by stereoselective SN2 fluorination of the THP-protected arabinoside followed by acidic deprotection. For the biological activity testing, two series of 4-substituted arabinonucleosides and 2'-deoxy- 2'-fluororibonucleosides were synthesized employing nucleophilic substitution or Pd-catalyzed cross-coupling reactions.
| Identifer | oai:union.ndltd.org:nusl.cz/oai:invenio.nusl.cz:346937 |
| Date | January 2016 |
| Creators | Konč, Juraj |
| Contributors | Hocek, Michal, Jindřich, Jindřich |
| Source Sets | Czech ETDs |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/masterThesis |
| Rights | info:eu-repo/semantics/restrictedAccess |
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