Synthesis of AZTpSpCX2ppSA and AZTpSpCX2ppSAZT: hydrolysis-resistant potential inhibitors of the AZT excision reaction of HIV-1 RT.
We report an efficient, one-flask route for synthesis of AZTpSpCX2ppSA and AZTpSpCX2ppSAZT, where X=H and X=F. This route makes use of the differential susceptibility to oxidation of H-phosphonate mono- and diesters, to allow a series of sequential reactions without requiring isolation of intermediates. These compounds are hydrolysis-resistant versions of the AZTppppA that results from excision of AZT by AZT-resistant HIV reverse transcriptase (RT). This family of compounds may therefore be useful in further study of the AZT excision reaction, as well as in drug design.
Han
Qianwei
Q
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, New Jersey 08854, USA.
Sarafianos
Stefan G
SG
Arnold
Eddy
E
Parniak
Michael A
MA
Gaffney
Barbara L
BL
Jones
Roger A
RA
D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006868:Hydrolysis; D015394:Molecular Structure; D010710:Phosphates / Q000737:chemistry; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
D010710:Phosphates; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase