Stereoselective hydroazidation of amino enones: synthesis of the ritonavir/lopinavir core

Ilaria Adamo; Fabio Benedetti; Federico Berti; Pietro Campaner

doi:10.1021/ol0524104

Stereoselective hydroazidation of amino enones: synthesis of the ritonavir/lopinavir core

Org Lett. 2006 Jan 5;8(1):51-4. doi: 10.1021/ol0524104.

Authors

Ilaria Adamo¹, Fabio Benedetti, Federico Berti, Pietro Campaner

Affiliation

¹ Department of Chemical Sciences, University of Trieste, Italy.

PMID: 16381565
DOI: 10.1021/ol0524104

Abstract

[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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Azides / chemistry*
HIV Protease Inhibitors / chemical synthesis*
HIV Protease Inhibitors / chemistry
Lopinavir
Pyrimidinones / chemical synthesis*
Pyrimidinones / chemistry
Ritonavir / chemical synthesis*
Ritonavir / chemistry
Stereoisomerism

Substances

Azides
HIV Protease Inhibitors
Pyrimidinones
Lopinavir
Ritonavir