The dynamic kinetic resolution of 2-phenyl-4-subsittuted-5(4<I>H</I>)-oxazolones 89a-g has been investigated as a method for the synthesis of optically active α-amino acid derivatives. The effects of lipase, [either Novozyme (<I>Candida antarctica </I>lipase B), or Lipozyme (<I>Rhizomucor miehei</I> lipase)], solvent, nucleophile, and the addition of external triethylamine to the reaction is described. When R<SUP>1</SUP> = Ph, an 88% yield and 98% enantiomeric excess (e.e.) of α-amino acid ester 96a was obtained with Novozyme<SUP>®</SUP> in acetonitrile as solvent. The synthesis of novel 5(4<I>H</I>)-oxazolones 129a-e, which are identified as key intermediates in the synthesis of a series of matrix metalloproteinase inhibitors 94, is described. Application of the lipase catalysed dynamic kinetic resolution conditions to 129a-e, afforded high yields (96%) and diastereomeric excesses (d.e.'s), (86%) of the resulting pseudodipeptides (2<I>R</I>,2'<I>S</I>)-127a-e and 130-132, by careful selection of the reaction conditions.(Figs. 1382A and 1382B).
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:642076 |
| Date | January 1999 |
| Creators | Brown, Stuart Andrew |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/13058 |
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