Stereocontrolled de novo synthesis of 2',3'-dideoxynucleosides via photoinduced electron transfer deoxygenation

2′,3′-Dideoxy- and 2 ′-deoxynucleosides are potent antiviral and anticancer agents. Their ready availability would further their development and application in such medicinal areas.; The current methodology for their de novo syntheses involves the coupling of a ribose derivative with a heterocyclic base to give the protected ribonucleoside. This ribonucleoside is then deoxygenated accordingly using a tin hydride reagent (nBu₃SnH). This approach has its drawbacks due to the toxicity of the tin hydride as well as the use of expensive protecting groups. As a result, its scale-up for pharmaceutical production is severely compromised.; The alternative de novo synthetic approach developed in this dissertation employs a photoinduced electron transfer (PET) deoxygenation of ribonucleosides to give the desired 2′,3′ -dideoxy- and 2′-deoxynucleosides. This approach bypasses the need for expensive protecting groups by using a more economical 3-(trifluoromethyl)benzoyl protecting group that also serves as the deoxygenation precursor. The PET deoxygenation step uses an improved carbazole photosensitizer, 3,6-dimethyl-9-ethylcarbazole (DMECZ), which gives the desired deoxy product in high yield.; A new synthesis of the DMECZ was also developed using a Corriu-Kumada nickel catalyzed cross-coupling reaction. The synthesis of DMECZ involved two steps, a high overall yield and easy separation of the product. The method not only found application in the synthesis of DMECZ, but to a variety of other 3,6-disubstituted carbazole derivatives.; From this work an improved route to the synthesis of β-2 ′,3′-dideoxy- and 2 ′-deoxynucleosides has been uncovered. The improved synthesis of DMECZ has also increased the availability of the photosensitizer, a class of molecules known also for their photochemical, medicinal, and polymeric properties.