Biotransformations

Harnessing Biotransformations

Our group has had a long lasting interest in using biotransformation to effect interesting and important chemical transformations. From the early days we were attracted by using biotransformations to achieve oxidation processes which were difficult by conventional methods. Illustrative of these reactions is the direct conversion of the natural product polygodiol to he drimane daniol sesquiterpene using a microbial oxidase Cunninghamella elegans [91]. Noteworthy in this example is the selective high-yielding oxidation at C-3 while simultaneously effecting selective reduction of the vinylic aldehyde substituent.

Our group was also the first to point out the power of using microbial dioxygenase Pseudomonas putida to disrupt the aromatic sextet by oxygenation of arenes to lead to useful building blocks for natural product synthesis [131, 163].

Recently we have shown that simple N-isovanillyltyramine derivatives undergo double oxidative biotransformations using the enzyme, tyrosinase, giving the corresponding hydroxylated dibenzoazocanes whereby we have formed a new C-C bond and installed a new hydroxyl group on one of the aromatic rings [694].

We have also used polymer-supported enzymes in continuous flow conditions. In this case pig liver esterase which we report in the first total synthesis of 2-aryl-2,3-dihydro-3-benzofurancarboxyamide neolignan, grossamide in 91% yield using a fully automated and scalable flow reactor [585].

Polymer-supported pig liver esterase was also used for the resolution of meso-diesters [472]. The enzyme can be recovered quantitatively from the reaction mixture by filtration and reused without significant loss of activity. Further transformation of the resulting enantiomerically enriched carboxylic acids through the application of polymer-supported reagents and scavengers provides a number of GABA-analogues.

Publications

1. The Diels–Alder route to drimane related sesquiterpenes; synthesis of cinnamolide, polygodial, isodrimeninol, drimenin and warburganal D.M. Hollinshead, S.C. Howell, S.V. Ley, M. Mahon, N.M. Ratcliffe and P.A. Worthington
J. Chem. Soc., Perkin Trans. 1, 1983, 1579-1589

2. Microbial oxidants in synthesis: a six step preparation of pinitol from benzene S.V. Ley, S. Taylor, F. Sternfeld Tetrahedron Lett198728, 225-226

3. Microbial oxidation in synthesis: preparation of (+)-and (-)-pinitol from benzene S.V. Ley and F. Sternfeld Tetrahedron 198945, 3463-3476

4. Enzymatic oxidative cyclisation reactions leading to dibenzoazocanes
F. Tozzi, S.V.Ley, M.O. Kitching, I.R. Baxendale Synlett 201013, 1919-1922

5. Preparation of the neolignan natural product grossamide by a continuous flow process I.R. Baxendale, C.M. Griffiths-Jones, S.V. Ley, G.K. Tranmer Synlett 2006, 427-430

6. Application of polymer-supported enzymes and reagents in the synthesis of γ-aminobutyric acid GABA analogues I.R. Baxendale, M. Ernst, W-R. Krahnert, S.V. Ley Synlett 2002, 1641-1644