Selective phosphorylation synthesis

Glycosyl transferase Oligosaccharide synthesis High selectivity Phosphorylated donors... 

Gajda, T., Zwierzak, A. Di-t-butyl phosphorobromidate. A new selective phosphorylating agent containing acid-labile protecting groups. Synthesis 1977, 623-625. 

The synthesis of the phosphoramidate pro-drug of 6-thio-7-deaza-2 -deoxyguanosine (23), a precursor to the potent inhibitor of human telomerase TDG-5 -triphosphate, has been achieved by selective phosphorylation of TGD with phenyl methoxyalaninyl phosphochloridate in the presence of iV-methyl-imidazole at -70°C. Compound (23) was effective in producing measurable levels ofTDG-TP in A539 cells. ... 

Ara-T, with significant activity against HSV-1 and -2, and varicella zoster virus (but little against cytomegalovirus) is selectively phosphorylated by HSV-induced deoxypyrimi-dine kinase, but not by thymidine kinase from uninfected cells. Thus inhibition of DNA synthesis affects viral replication, but not the growth of normal cells, which explains the observed selective toxicity. 

Kawana,M. and Kuzuhara, H. (1984) The synthesis of partially-protected 2 -deoxyribonucleotide dimers by the selective phosphorylation of stannylated nucleosides. Bull. Chem. Soc. Japan 57, 3317-3320. 

Fig. 2. Synthesis of uma2enil (18). The isonitrosoacetanihde is synthesized from 4-f1iioroani1ine. Cyclization using sulfuric acid is followed by oxidization using peracetic acid to the isatoic anhydride. Reaction of sarcosine in DMF and acetic acid leads to the benzodiazepine-2,5-dione. Deprotonation, phosphorylation, and subsequent reaction with diethyl malonate leads to the diester. After selective hydrolysis and decarboxylation the resulting monoester is nitrosated and catalyticaHy hydrogenated to the aminoester. Introduction of the final carbon atom is accompHshed by reaction of triethyl orthoformate to...

IFN-a, -P and -y are all known to induce the enzyme in various animal cells. However, in human epithelial cells the kinase is induced only by type I interferons, whereas none of the interferons seem capable of inducing synthesis of the enzyme in human fibroblasts. The purified kinase is highly selective for initiation factor eIF-2, which it phosphorylates at a specific serine residue. 

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