Pyrimidine, 5-amino-4- nucleosides

Balzarini J, Perez-Perez M-J, San-Felix A, Schols D, Perno C-F, Vandamme A-M, Camarasa M-J, De Clercq E. 2, 5 -Bis-0-(tert-Butyldimethylsilyl)-3 -spiro- 5" -(4" -amino-1", 2" -oxathiole-2", 2" -dioxide)pyrimidine (TSAO) nucleoside analogues highly selective inhibitors of human immunodeficiency virus type 1 that are targeted at the viral reverse transcriptase. Proc Natl Acad Sci USA 1992 89 4392-4396. 

Determination of in vitro growth inhibitory activity of several thieno[3,4-d]pyrimidine C-nucleosides against L1210-C1, sarcoma 180, and HL60 cell lines indicated that 4-amino-7-/3-D-ribofuranosylthieno[3,4-t/Jpyrimidine 377 is by far the most cytotoxic, with IC50 values of 0.0046, 0.015 and 0.0092 respectively (93JHC509). 

Compound classes labeled by heterogeneous metal-catalyzed tritium exchange from water include amino acids, peptides and proteins, sugars, polycyclic aromatic hydrocarbons, purines, pyrimidines and nucleosides, alkyl-substituted aromatics, alicyclic compounds and steroids, A-heterocycles and anilines and some O- and 5-heterocycles. The method is firmly fixed in the repertoire of methods of the commercial custom labeling industry. 

Aminohexose Nucleosides. The 4-aminohexose nucleosides (128—140) are Hsted in Table 7 (1—4,240—242). A biosynthetic relationship between the 4-aminohexose peptidyl nucleoside antibiotics and the pentopyranines has been proposed (1). The 4-aminohexose pyrimidine nucleoside antibiotics block peptidyl transferase activity and inhibit transfer of amino acids from aminoacyl-tRNA to polypeptides. Hikizimycin, gougerotin, amicetin, and blasticidin S bind to the peptidyl transferase center at overlapping sites (243). 

Just as proteins are biopolymers made of amino acids, nucleic acids are biopolv-mers made of nucleotides joined together to form a long chain. Each nucleotide is composed of a nucleoside bonded to a phosphate group, and each nucleoside is composed of an aldopentose sugar linked through its anomeric carbon to the nitrogen atom of a heterocyclic purine or pyrimidine base. 

Treatment of the allylic sulfoxide 1227 a with diisopropylethylamine (DIPEA) or of 1227 b with N-trimethylsilyldiethylamine 146 and TMSOTf 20 leads in ca. 90% yield to the quaternary amino derivatives 1228 and 1229 and HMDSO 7 [36] (Scheme 8.15). Tetramethylene sulfoxide 1230 reacts with silylated thymine 1231 in the presence of three equivalents of TMSOTf 20 to give the 4 -thio-nucleoside analogue 1232 and HMDSO 7 [37]. Other silylated pyrimidine, pyridine, and purine bases react analogously with cyclic sulfoxides to give 4 -thio-nucleoside analogues [37, 37a, 38]. 

Deprotonation provides the necessary electron push to kick out the electron pair joining C(6) with the nitrobenzene oxygen. If, however, N(l) is alkylated (as with the nucleosides and nucleotides), OH catalysis is much less efficient since it now proceeds by deprotonation from N(3) (with the uracils) or from the amino group at C(4) (with the cytosines). In these cases the area of deprotonation is separated from the reaction site by a (hydroxy)methylene group which means that the increase in electron density that results from deprotonation at N(3) is transferable to the reaction site only through the carbon skeleton (inductive effect), which is of course inefficient as compared to the electron-pair donation from N(l) (mesomeric effect) [26]. Reaction 15 is a 1 1 model for the catalytic effect of OH on the heterolysis of peroxyl radicals from pyrimidine-6-yl radicals (see Sect. 2.4). 

The 2-aminochromene moiety can influence the other types of biological activity. A series of pyrimidine nucleosides 313, containing a 2-amino-5,6,7,8-tetrahydrochromene fragment, reveal activity against Leishmania donovani (06BML5047) (IC50 about 1-10 p). 

The analysis of a variety of compounds of biochemical interest have been reported. Some of these were given in the preceding section. The versatility of RPC can be shown, however, by considering the large number of applications given to the analysis of purine and pyrimidine bases, their nucleosides and nucleotides, as well as the determination of amino acids and their corresponding peptides and proteins. 

Upon formation of the nucleosides from 5-aminopyrido[2,3-crystallographic studies. They showed that the bond length of C(l )-N(8) is... 

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