5-Bromo (or chloro)-6-azido-5,6-dihydro-2′-deoxyuridine and -thymidine derivatives with potent antiviral activity

Interplay between Conjugation and Size-Driven Delocalization Leads to Characteristic Properties of Substituted Thymines

“…For instance, the LUMO of Thy (Figure and Figure S1) is delocalized along the C 6 C 5 C 4 O region and the largest coefficient of the LUMO is on C 6 followed by C 4 and none at all on C 2 . This suggests that nucleophilic addition is most likely to happen on C 6 rather than on the carbonyl carbons C 4 and C 2 , and this is confirmed by experiments. ,− For instance, when thymidine reacts with N -bromosuccinamide and sodium azide, addition of the nucleophile (azide) takes place on C 6 . This trend can be expected to persist in the sulfur-substituted thymines based on the strong similarity of their LUMOs with that of Thy (Figure and Figure S1).…”

“…30,50−52 For instance, when thymidine reacts with N-bromosuccinamide and sodium azide, addition of the nucleophile (azide) takes place on C 6 . 52 This trend can be expected to persist in the sulfur-substituted thymines based on the strong similarity of their LUMOs with that of Thy (Figure 2 and Figure S1). Interestingly, in 4tThy, where conjugation and size-driven delocalization assist each other, the LUMO energy is significantly lowered as compared to Thy and thus 4tThy can be expected to be a stronger electrophile as compared to Thy.…”

Self-assembling of dihydroxypropyl 5,6-dihydrothymine derivatives

“…5,6-Dihydro pyrimidine nucleosides have been calling attention after was found that 5-methyl-5,6-dihydrouridine in the chromosomal RNA of the rat ascites tumor [8]. 5,6-Dihydro-2 0 -deoxyuridine derivatives exhibited a broad spectrum of antiherpes activity against HSV-1, HSV-2, HCMV, and VZV [9].…”