The N-Hydroxymethyl Group as a Traceless Activating Group for the CAL-B-Catalysed Ring Cleavage of β-Lactams A Type of Two-Step Cascade Reaction /
An efficient enzymatic two-step cascade procedure has been devised for rapid access to diverse amino acids from N-hydroxymethyl-β-lactams; representative amino acids include the antifungal agent cispentacin, intermediates for the taxol side-chain, and assorted cathepsin inhibitors. When CAL-B-cataly...
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| Dokumentumtípus: | Cikk |
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Wiley-VCH
2016
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| Sorozat: | EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
2016 No. 15 |
| doi: | 10.1002/ejoc.201600234 |
| mtmt: | 3078419 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/9898 |
| Tartalmi kivonat: | An efficient enzymatic two-step cascade procedure has been devised for rapid access to diverse amino acids from N-hydroxymethyl-β-lactams; representative amino acids include the antifungal agent cispentacin, intermediates for the taxol side-chain, and assorted cathepsin inhibitors. When CAL-B-catalysed hydrolyses of racemic N-hydroxymethyl-β-lactams were performed with H2O (0.5 equiv.) in iPr2O at 60 °C, relatively quick (vs. non-activated counterparts) and enantioselective (E > 200) ring cleavage reactions took place. As the ring-opened amino acids formed, the hydroxymethyl group, as a traceless activating group, underwent spontaneous in situ degradation. Consequently, the desired β-amino acid and unreacted N-hydroxymethyl-β-lactam enantiomers (ee > 95 %) were formed. The formation of polymers, induced by liberation of formaldehyde, was successfully restricted by the addition of benzylamine as a capture agent, to the enzymatic reactions. An efficient enzymatic two-step cascade procedure was devised for CAL-B-catalysed hydrolysis of racemic N-hydroxymethyl-β-lactams. Conditions in which the hydroxymethyl group serves as a traceless activating group (E > 200), giving desired β-amino acid along with unreacted starting lactam enantiomers (ee > 95 %) were identified; polymerization was controlled by addition benzylamine addition. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
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| Terjedelem/Fizikai jellemzők: | 2647-2652 |
| ISSN: | 1434-193X |