Synthesis of both RP and SP enantiomers of unsymmetrical methylphosphonates based on a new approach utilizing a P-ester bond with α-hydroxyacids |
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| Institution: | 1. Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Heteroorganic Chemistry, 90-363 Łódź, Sienkiewicza 112, Poland;2. Jan Długosz University, Institute of Chemistry and Environmental Protection, 42-201 Częstochowa, Armii Krajowej 13/15, Poland;1. Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA;2. Department of Chemistry, Middle East Technical University, 06800 Ankara, Turkey;1. Department of Biochemistry and Molecular Biology, University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA;2. Department of Chemistry, University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA;1. SAITO Research Center, Peptide Institute, Inc., Ibaraki, Osaka 567-0085, Japan;2. Graduate School of Pharmaceutical Science, Osaka University, Suita, Osaka 565-0871, Japan;3. Graduate School of Science, Osaka University, Toyonaka, Osaka 560-0043, Japan;1. Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 5 Murmans’ka str., Kyiv 02660, Ukraine;2. Department of Organic Chemistry, National Technical University of Ukraine “Kyiv Polytechnic Institute”, 37, Prospect Peremogy, Kyiv 03056, Ukraine |
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| Abstract: | Condensation of methyl methylphosphonochloridate with the dilithium salt of 2-methyllactic acid gave P-racemic methylphosphonates which unexpectedly contained two units of α-hydroxyacid linked via carboxylic ester bond. The racemic mixture was chromatographically separated via diastereomeric salts with quinine or cinchonine to give, based on the X-ray analysis, pure (RP)-(+) and (SP)-(−) enantiomers. Both enantiomers were immobilized on the ArgoGel®–OH solid support. Condensation of methyl methylphosphonochloridate with α-hydroxyacid methyl esters 2-methyllactate, (SC)-(−)-lactate, methyl (SC)-(+) and (RC)-(−)-mandelates] gave chromatographically inseparable 1:1 mixtures of diastereomers in 63–69% yields. A basic hydrolysis of the latter resulted in a selective and unexpected cleavage of the P–OMe group in a quantitative yield (SC)-(+) and (RC)-(−)-mandelates, (SC)-(−)-lactate] or simultaneous cleavages of P–OMe and C(O)OMe groups (2-methyllactate). |
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