Synthetic Study Of Anti-aids Drug Ritonavir And Its Derivatives

Ritonavir, the chemical name of which is(2S,3S,5S)-5-[N-[N-[[N-methyl-N-[(2-isopropyl-4-thiazolyl)methyl]amino]carbonyl]valyl]amino]-2-[N-[(5-thiazolyl)methoxy carbonyl]amino]-1,6-diphenyl-3-hydroxyhexane, was developed by Abbott company as a HIV protease inhibitor in 1994 and now is primarily used for the treatment of AIDS. On the basis of the previous work of our group, ritonavir was successfully prepared from(2S)-5-amino-2-(N,N-dibenzyl)amino-3-oxo-1,6-diphenyl-2-hexene via 8 steps, which include two-step reduction, Boc-protecting reaction of 5-amino, benzyl-deprotection of 2-amino, succinic saltation, 2-amidation, Boc-deprotection of 5-amino, and 5-amidation(total yield about 39%, purity > 99%). I finally obtained an efficient, simple and green synthetic route of ritonavir, which could meet the needs of industrial production. Ritonavir and its intermediates were all confirmed by NMR and so on.On the basis of the synthetic route of ritonavir, a series of ritonavir derivatives were successfully prepared from(2S,3S,5S)-3-hydroxy-2-amino-5-(t-butoxycarbonyl)amino-1,6-diphenylhexane via 3 steps, which include 5-amidation, deprotection of 2-amino and 2-amidation. I finally obtained a series of ritonavir derivatives, which could meet the needs of bioacitivity study of the HIV protease inhibitor prodrugs.