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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
Author(s) -
Popp Alfred,
Gilch Andrea,
Mersier AnneLaure,
Petersen Hermann,
RockingerMechlem Jodoca,
Stohrer Jürgen
Publication year - 2004
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200303184
Subject(s) - chemistry , enantiopure drug , kinetic resolution , candida antarctica , nucleophile , stereochemistry , nucleoside , solvolysis , resolution (logic) , enzyme , lipase , organic chemistry , combinatorial chemistry , hydrolysis , enantioselective synthesis , catalysis , artificial intelligence , computer science
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.