No description available.

No description available.

Thesis (Ph. D.)--University of Lund, 1995. / Published dissertation.

Thesis (Ph. D.)--University of Lund, 1995. / Published dissertation.

The key intermediate 6-amino-7-iodo-7-deazapurine 3'-deoxy-3'-fluororibonucleoside was synthesized using multistep sequence of several reactions, which started from the commercially available D-xylose and 6-chloro-7-deazapurine. The synthetic strategy was based on fluorination of sugar and glycosylation with corresponding nucleobase afterwards. The fluorination of 5-protected-1,2-isopropylidine xylose with different protecting groups at position 5 always led to elimination. It was later discovered that isopropylidine forces the conformation, which is unfavorable for substitution. During the extensive optimization it was also found out that DAST appears to be an optimal fluorinating agent. Fluorination was performed on 2,3-unprotected xylose, which was subsequently used for glycosylation. After several unsuccessful attempts on "protection group free" glycosylation, Vorbrüggen glycosylation was successful and gave desired 3'-fluoro nucleoside in good yield. However, benzoyl group had to be introduced into position 2'. The protected nucleoside was then aminated and simultaneously deproctected with solution of aqueous NH3 and 1,4-dioxane. The obtained key intermediate was used for synthesis of a small series of desired 6-amino-7-hetaryl nucleoside using Pd-catalyzed Suzuki reaction under aqueous...

No description available.

No description available.

Thesis advisor: Larry W. McLaughlin / Thesis advisor: Mary F. Roberts / Nucleic acids are the only biopolymers capable of encoding and transferring information, this property has placed them at the fundamental core of all living organisms, and made them a topic of intense research for over a century. The former studies in our laboratory on simplified nucleic acid backbones provided insight into how we might rationally alter nucleic acid structure into one that possesses properties not observed in natural DNA and RNA. Here the work began as an investigation into rigidified nucleic acid systems capable of functioning as DNA. The first rigidified nucleic acid system we designed, the cyclo-2'-deoxynucleic acids, has a linkage between the C5' of the ribose sugar and base to lock the ӽ angle into the similar angle as the native nucleoside. These rigidified bases show great impact towards the DNA structure, destabilizing double helix formation. This in fact can also be found in nature to inhibit the TATA binding protein associating with its target region. The next generation of rigidified nucleosides has an extended 7-membered ring instead of the 6-membered ring that was present in the first generation to push the base closer to the helical center. Both diastereomers of the ring-expanded-cyclo-2'-deoxyadenosine have been successfully synthesized and characterized and are ready to perform further studies. The third system is the hydroxymethyl-cyclo-nucleosides. The modified nucleosides in this project not only have the same linkage as the cyclo-nucleosides in the first system to restrict the base rotation, but also have an extra carbon (C6') to give the backbone more flexibility which might better stabilize a double helix than the first generation. / Thesis (PhD) — Boston College, 2012. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Five pyrimidine C-nucleosides were prepared via Heck-type coupling reactions. These derivatives are designed to mimic dC and dU (or T). The minor groove O2 carbonyl in each derivative is replaced by a hydrogen, a fluorine, or a methyl group. The hydrogen-substituted dC analogue was converted into a 2’,3’-dideoxynucleoside, which was converted into a 5’-triphosphate derivative. The other two dC analogues were transformed into 5’-triphosphate derivatives immediately after Heck coupling reactions. These analogues will allow an examination of the nature and role of minor groove interactions between incoming triphosphates and various polymerases. / Thesis (MS) — Boston College, 2008. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis (Ph. D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2006. / Barefield, E. Kent, Committee Member ; Beckham, Haskell W., Committee Member ; Doyle, Donald F., Committee Member ; Weck, Marcus, Committee Member ; Seley, Katherine L., Committee Chair.