An efficient, scalable synthesis of the HIV reverse transcriptase inhibitor Ziagen (1592U89).
Ziagen, (1S,cis)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]- 2-cyclopentene-1-methanol, was synthesized from (1S,4R)-azabicyclo[2.2.1]hept-5-en-3-one by efficient processes which bypass problematic steps in earlier routes. 2-Amino-4,6-dichloro-5-formamidopyrimidine is a key intermediate which makes possible an efficient construction of the purine from a chiral cyclopentenyl precursor.
Daluge
S M
SM
Division of Medicinal Chemistry, Glaxo Wellcome Inc., Research Triangle Park, North Carolina 27709, USA.
Martin
M T
MT
Sickles
B R
BR
Livingston
D A
DA
D019380:Anti-HIV Agents / Q000138:chemical synthesis*; D018360:Crystallography, X-Ray; D015224:Dideoxynucleosides / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis*; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir