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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Directed reductive amination of beta-hydroxy-ketones: convergent assembly of the ritonavir/lopinavir core
Dirk Menche1, Fatih Arikan, Jun Li
1Gesellschaft für Biotechnologische Forschung mbH, Medizinische Chemie, Mascheroder Weg 1, D-38124 Braunschweig, Germany. dirk.menche@helmholtz-hzi.de
Abstract:
An efficient procedure for the directed reductive amination of beta-hydroxy-ketones (3) for the stereoselective preparation of 1,3-syn-amino alcohols (6) is reported. The operationally simple protocol uses Ti(iOPr)4 for coordination of the intermediate imino alcohol (5) and PMHS as the reducing agent. The method was expanded to an asymmetric aldol reductive amination sequence to allow a highly convergent synthesis of the hydroxy-amine core of the HIV-protease inhibitors ritonavir and lopinavir. [reaction: see text].
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