Preparative-scale high-performance liquid chromatographic separation and purification of 3'-azido-3'-deoxythymidine-5'-phosphate.
Crude 3'-azido-3'-deoxythymidine-5'-phosphate (AZT-P), obtained from direct phosphorylation of 3'-azido-3'-deoxythymidine (azidothymidine, AZT), was separated and purified by isocratic preparative high-performance liquid chromatography. The components in a 2.5-g load of crude AZT-P, obtained from work-up of the phosphorylation reaction, were separated in 50 min to give 1.8 g of 99.5% pure AZT-P. AZT-P was analyzed by high-performance liquid chromatography and by high-resolution nuclear magnetic resonance (1H, 13C, 31P) spectroscopy. The practical and rapid preparative chromatographic method is being applied to the purification of AZT-P and other antiretroviral dideoxynucleotides, used as intermediates in the synthesis of target-directed experimental drugs for the treatment of AIDS.
Turcotte
J G
JG
Department of Medicinal Chemistry, University of Rhode Island, Kingston 02881.
Pivarnik
P E
PE
Shirali
S S
SS
Singh
H K
HK
Sehgal
R K
RK
Macbride
D
D
Jang
N I
NI
Brown
P R
PR
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D054306:Dideoxynucleotides; D013942:Thymine Nucleotides; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000378:metabolism
D054306:Dideoxynucleotides; D013942:Thymine Nucleotides; C057287:3'-azido-3'-deoxythymidine 5'phosphate; D015215:Zidovudine