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
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...
| Published in: | Advanced Synthesis & Catalysis |
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| Main Authors: | , , , , , |
| Format: | Article in Journal/Newspaper |
| Language: | English |
| Published: |
Wiley
2004
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| Subjects: | |
| 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 |
| Summary: | 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. |
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