3 -Azido-3 -deoxythymidine phosphonates

Azido-3 -deoxythymidine 5 -[(methyl 5-acetamido-3,5-dideoxy-D-g/ycero-a-D-ga/acto-non-2-ulopyranosylonate) phosphonate]... 

It has been shown that coupling of the ethyl phosphinate A with 5 -azido-2 -methoxy-5 -deoxythymidine B to afford the corresponding phosphon-amidate proceeds with retention of configuration at the phosphorus atom. Determine the configuration of reactants and product. 

A chemoenzymatic synthesis of the P-a-methyl 2 -deoxynucleoside triphosphates 122 has been described which involves reaction of the 5 -0-(methylpho-sphonyl)-N-protected nucleosides with pyrophosphate in the presence of CDI. Removal of the base protection by treatment with penicillin amidase gave compounds 122 leaving the labile a-methylphosphonate intact. A number of 2 -deoxythymidine 5 -triphosphate and 3 -azido-2, 3 -dideoxythymidine 5 -tripho-sphate analogues (123) containing a hydrophobic phosphonate group have also been synthesised and evaluated as substrates for several viral and mammalian polymerases. Some y-ester (124) and y-amide (125) derivatives of dTTP and 3 -azido-2, 3 -dideoxythymidine 5 -triphosphate (AZTTP) were also synthesized and studied. The y-phenylphosphonate triphosphate 126 and its conjugation to biotin and fluorescein labels has also been described. 

Azido-2, 3 -dideoxythymidine-5 -H-phosphonate was obtained by reacting 3 -azido-2, 3 -deoxythymidine with PCI3 and subseqnent hydrolysis (see Appendix) [184-186]. 

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