The enzyme transketolase (TK) [E.C.2.2.1.1] catalyses the stereoselective transfer of a two-carbon ketol unit from a donor substrate such as lithium hydroxypyruvate (LiHPA, i) to an α-hydroxyaldehyde. Research into the use of TK from <I>Escherichia coli </I>as a process catalyst for asymmetric carbon-carbon bond formation has required the development of synthetic routes to novel acceptor substrates. The preparation of novel α-hydroxyaldehydes in enantiomerically pure form from chiral pool α-hydroxy-or α-amino acids, and of racemic α-hydroxy-aldehydes of utility in the synthesis of natural produce analogues, is described. Formerly, biotransformations mediated by TK involved the use of an excess of aldehyde substrate in buffered aqueous solution. An alternative protocol is presented, in which the biotransformations are performed in unbuffered medium; the natural pH change during the biotransformation is offset by use of a pH autotitrator to maintain the solution pH at the process optimum of 7.0. The synthetic utility of the chiral triols produced from TK-mediated biotransformations has been demonstrated through the development of synthetic routes to the natural product nectrisine, ii, and the <I>N-</I>hydroxypyrrolidine sugar analogue iii from the triols iv and v, available <I>via</I> TK-mediated condensation of LiHPA with the appropriate α-hydroxyaldehyde.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:652716 |
| Date | January 1997 |
| Creators | Humphrey, Andrew Joseph |
| Publisher | University of Edinburgh |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://hdl.handle.net/1842/12093 |
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