Enzymatic Kinetic Resolution of 1,3‐Dioxolan‐4‐one and 1,3‐Oxathiolan‐5‐one Derivatives: Synthesis of the Key Intermediate in the Industrial Synthesis of the Nucleoside Reverse Transcriptase Inhibitor AMDOXOVIR

• Published in: Advanced Synthesis & Catalysis
• Main Authors: Popp, Alfred, Gilch, Andrea, Mersier, Anne‐Laure, Petersen, Hermann, Rockinger‐Mechlem, Jodoca, Stohrer, Jürgen
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2004
• Subjects: Antarc*; Antarctica
• Online Access: http://dx.doi.org/10.1002/adsc.200303184; https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fadsc.200303184; https://onlinelibrary.wiley.com/doi/pdf/10.1002/adsc.200303184

Abstract The resolution of racemic 1,3‐dioxolan‐4‐one and 1,3‐oxathiolan‐5‐one derivatives such as (4‐oxo‐1,3‐dioxolan‐2‐yl)methyl 2‐methylpropanoate ( 2 ) by enzymatic solvolysis was investigated. The resolution of 2 , a precursor for the synthesis of the nucleoside reverse transcriptase inhibitor Amdoxovir, was optimized in terms of solvent/nucleophile, reaction conditions, and enzyme. The use of lipase from Candida antarctica B (CALB) and methanol as nucleophile and solvent resulted in an effective resolution and the product ( R )‐2 could be easily isolated. Products of substrate decomposition can be isolated and reused for the synthesis of racemic 2 . The broad range of application for this enzymatic resolution was demonstrated by the resolution of further substrates with different substitution patterns. This process gives a new and unprecedented access to enantiopure 1,3‐dioxolan‐4‐ones and 1,3‐oxathiolan‐5‐ones.