Stereoselective hydroazidation of amino enones: synthesis of the ritonavir/lopinavir core.
[reaction: see text] The base-catalyzed hydroazidation of alpha'-amino alpha,beta-unsaturated ketones with in situ generated hydrazoic acid was found to proceed with high stereoselectivity in favor of the syn product. The stereoselectivity is controlled by the configuration of the enone and syn/anti ratios up to 7:1 were obtained with secondary and tertiary amines at low temperature. By this route the diamino alcohol core of HIV-PR inhibitors ritonavir and lopinavir was synthesized in 37% yield from phenylalanine.
Adamo
Ilaria
I
Department of Chemical Sciences, University of Trieste, Italy.
Benedetti
Fabio
F
Berti
Federico
F
Campaner
Pietro
P
D001386:Azides / Q000737:chemistry*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D061466:Lopinavir; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry; D019438:Ritonavir / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D001386:Azides; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir