Enantiomerically pure β-branched-α-amino acids are important synthetic targets and a challenging group of compounds to prepare. A series of diastereoisomers of β-methylphenylalanine analogues have been prepared in enantiomerically pure form using a combination of chemo-and bio-catalysis. Starting from L-threonine methyl ester and proceeding <i>via </i>the vinyl halide with Suzuki chemistry, a range of β,β-disubstituted didehydroamino acids were obtained as their (<i>Z</i>)-isomers. Asymmetric hydrogenation of these alkenes, using either the [Rh(<i>R,R</i>)-Et-DuPhos(COD)BF<sub>4</sub> or [Rh(<i>S,S</i>)-Et-DuPhos(COD)]BF<sub>4</sub> catalyst, followed by hydrolysis, yielded two of the four possible sets of diastereoisomers of the β-branched amino acid. Subsequent stereoinversion, using a stereoselective amino acid oxidase in combination with a non-selective reducing agent, furnished the remaining two sets of diastereomers.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:661348 |
| Date | January 2004 |
| Creators | Roff, Geoffrey John |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/12879 |
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