Pyrimidines azido-substituted

Irradiation of azido-substituted pyrazines and pyrimidines bearing strong electron-donating substituents in the presence of a base, such as MeONa or diethylamine, resulted in ring expansion with formation of 1,3,5-triazepines (Scheme 38) <1990CC723>. A similar transformation was observed on irradiation of a series of 6-azidouracils in the presence of a primary or a secondary amine <1984J(P1)1719>. 

Activity of 3 -Fluoro- and 3 -Azido-Substituted Pyrimidine 2 ,3 -Dideoxynucleoside Analogues, Biochem. Pharmacol. 37 2847 (1988). 

Ethyl 3-azido-l-methyl-177-indole-2-carboxylate 361 is prepared in 70% yield by diazotization of amine 360 followed by substitution of the created diazonium group with sodium azide. In cycloadditions with nitrile anions, azide 361 forms triazole intermediates 362. However, under the reaction conditions, cyclocondensation of the amino and ethoxycarbonyl groups in 362 results in formation of an additional ring. This domino process provides efficiently 4/7-indolo[2,3-i ]l,2,3-triazolo[l,5- ]pyrimidines 363 in 70-80% yield (Scheme 57) <2006TL2187>. 

The first marketed NRTI for HIV was zidovidine (Retrovir, 6.10) (Figure 6.19). Zidovidine is a pyrimidine nucleoside analogue. Substitution of the 3 -hydroxyl with an azido group makes chain elongation of the DNA strand impossible upon zidovidine incorporation. Although nucleotides are the required substrate of RT, most NRTIs are nucleo. Vfe.s. Zidovidine and other NRTIs are transported into a cell without any 5 -phosphates. Once in a cell, the... 

Azido-6-formyl-l,3-dimethyluracil (473) is cyclized with hydrazines to form l-substituted-5,7-dimethyl-1 //-pyrazolo[3,4-. 

Base-induced ring-opening of pyrimidines, or nitrene formation (as in the pyrolysis of azido-pyrimidines) can give imidazoles (see CHEC-I). There are also a few examples of photochemical ring contraction. For example, 4-heteroaryl substituted 1,4- (or 3,4-)dihydropyrimidines give some imidazole products (Equation (76)) <83RTC364>. 

Villalgordo et al. [22, 23] as well as Gayo and Suto [25] developed a strategy to cleave pyrimidines from the solid support. After oxidation of the thioether-linkage 17, aromatic substitution of the sulfonyl unit was performed with different N-nucleophiles as amines and azides to give free amino- or azido-pyrimidines 19 (Scheme 16.5). To demonstrate the stability of the linker, the resin-bound derivatives were subjected to different reactions such as saponification, ester reduction, acid chloride formation or Mitsunobu alkylation. A similar approach was presented later on by Hwang and Gong in the SPOS of 2-aminobenzoxazoles [26]. 

The 4 -position of nucleosides has previously been ignored as a site of modification when seeking inhibitors of HTV. Yet many substitutions at this position are capable of inducing potent anti-HIV activity. Furthermore, in the case of 4 -azido-2 -deoxynucleosides, this activity is maintained throughout a broad series of both purine and pyrimidine bases. Such scope of activity in a single nucleoside series is very rare. 

AZIDO, 3 -AMINO, 2, 3 -UNSATURATED, 2, 3 -DIDEOXY, AND 5-SUBSTITUTED ANALOGUES OF PYRIMIDINE NUCLEOSIDES... 

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