[Novel synthesis and spectral characterization of nelfinavir].
An efficient and environmentally friendly procedure for the one-pot synthesis of (3S,4aS,8aS)-2-((2R,3R)-3-amino-2-hydroxy-4-(phenylthio)butyl)- N-tert -butyl-decahydroisoquinoline-3-carboxamide(VII), the intermediate of nelfinavir, was described, and activating ester was applied to getting nelfinavir(IX). Under the catalysis of potassium hydroxide, benzyl (R)-1-((S)-oxiran-yl)-2-(phenylthio) ethyl carbamate was obtained(IV) in methanol. Then IV and (3S,4aS,8aS)- N-tert -butyl-decahydroisoquinoline-3-carboxamide(V) were refluxed in methanol until the reaction was finished. Potassium hydroxide(w(KOH) = 40%) in water was added to remove benzyloxycarbonyl group in water bath with a yield of 89.0%. 3-acetoxy-2-methylbenzoic acid-succinimide ester(II) reacted with VII and acetyl group was removed by dense aqueous ammonia, giving nelfinavir(IX). The vibrations of functional groups of thiIIs compound corresponding to the main infrared absorption peaks were discussed. The molecular ion and quasi molecular ion peaks were obtained via MALDI-TOF MS, and 1H NMR and 13CNMR shifts of this compound were assigned by means of DEPT(distortionless enhancement by polarization transfer spectrum), HMBC(1H detected heteronuclearmultiple bond correlation spectrum), HSQC(1H detected heteronuclear single-quantum coherence spectrum) and DQF-COSY(double-quantum filtered-correlated spectroscopy). The results provided useful information for structure characterization and quality control of nelfinavir.
Yan
Jian-Hui
JH
School of Life Science and Technology, Beijing Institute of Technology, Beijing 100081, China. yanjianhui@bit.edu.cn
Yao
Guo-Wei
GW
Yang
Li-Na
LN
Hu
Gao-Fei
GF
Yang
Xin-Lin
XL
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D019888:Nelfinavir / Q000138:chemical synthesis* / Q000737:chemistry*; D013055:Spectrophotometry, Infrared
D019380:Anti-HIV Agents; D019888:Nelfinavir