Abstract
Chiral methyl-branched carboxylic acids or the corresponding alcohols of high enantiomeric purity are valuable intermediates for the synthesis of many pharmaceuticals, pesticides, and natural substances such as phero-mones. Often, compounds of a very high enantiomeric excess (>99.5% ee) are needed. Various methyl-branched carboxylic acids have been synthesized by chemical methods such as diastereoselective alkylation of alkylamide enolates bearing a chiral auxiliary (1). However, a loss in enantiomeric excess of about 2% ee is often associated with the final hydrolytic removal of the chiral auxiliary to release the chiral alkylated acid. This has been noted, for instance, with the currently popular auxiliary pseudo-ephe-drine (2), and much work has been devoted to overcome this obstruction, albeit with limited success so far (3).
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References
Högberg, H.-E. (1995) Alkylation of amide enolates, in Houben-Weiy Methods of Organic Chemistry, Vol. E21a, Stereoselective Synthesis (Helmchen G., Hoffmann, R. W., Mulzer, J., Schaumann, E., eds.),Thieme, Stuttgart, pp. 791–915.
Myers, A. G., Yang, B. H., Chen, H., and Gleason, J. L. (1994) Use of pseu-doephedrine as a practical chiral auxiliary for asymmetric synthesis. J. Am. Chem. Soc. 116, 9361,9362.
Myers, A. G., Yang, B. H., Chen. H., McKinstry, L., Kopecky, D. J., and Gleason, J. L. (1997) Pseudoephedrine as a practical chiral auxiliary for the synthesis of highly enantiomerically enriched carboxylic acids, alcohols, aldehydes, and ketones. J. Am. Chem. Soc. 119, 6496–6511.
Edlund, H., Berglund, P., Jensen, M., Hedenström, E., and Högberg, H.-E. (1996) Resolution of 2-methylalkanoic acids. Enantioselective esterification with long chain alcohols catalysed by Candida rugosa lipase. Acta Chem. Scand. 50, 666–671.
Allen, C. F. and Kalm, M. J. (1963) 2-Methylenedodecanoic acid, in Organic Syntheses, coll. vol. IV (Rabjohn, R., ed.), Wiley, New York, p. 618, Note. 2.
Sonnet, P. E. and Baillargeon, M. W. (1989) Synthesis and lipase catalyzed hydrolysis of thiolesters of 2-, 3-, and 4-methyl octanoic acids. Lipids 24, 434–437.
Dinh, P. M., Williams, J. M. J., and Harris, W. (1999) Selective racemisation of esters: relevance to enzymatic hydrolysis reactions. Tetrahedron Lett. 40, 749–752.
Vörde, C., Högberg, H. E., and Hedenström, E. (1996) Resolution of 2-methyl-alkanoic esters: enantioselective aminolysisby (R)-1-phenylethylamine of ethyl 2-methyloctanoate catalysed by lipase B from Candida antarctica. Tetrahedron: Asymmetry 7, 1507–1513.
Stecher, H. and Faber, K. (1997) Biocatalytic deracemizationt echniques: dynamic resolutions and stereoinversions. Synthesis 1–16.
Ebbers, E. J., Ariaans, G. J. A., Houbiers, J. P. M., Bruggnink, A., and Zwanenburg, B. (1997) Controlled racemization of optically active organic compunds: prospects for asymmetric transformation. Tetrahedron 53, 9417–9476.
Montero, S., Blanco, A., Virto, M. D., Landeta, L. C., Agud, I., Solozabal, R., et al. (1993) Immobilization of Candida rugosa lipase and some properties of the immobilized enzyme. Enzyme Microb. Technol. 15, 239–247.
Zaks, A. and Klibanov, A. M. (1985) Enzyme-catalyzed processes in organic solvents. Proc. Natl. Acad. Sci. USA 82, 3192–3196.
Valivety, R. H., Halling, P. J., Peilow, A. D., and Macrae, A. R. (1992) Lipases from different sources vary widely in dependence of catalytic activity on water activity. Biochim. Biophys. Acta 1122, 143–146.
Kvittingen, L., Sjursnes, B., Halling, P., and Anthonsen, T. (1992) Mixing conditions for enzyme catalysis in organic solvents. Tetrahedron 48, 5259–5264.
Laane, C., Boeren, S., Vos, K., and Veeger, C. (1987) Rules for optimization of biocatalysis inorganic solvents. Biotechnol. Bioeng. 30, 81–87.
Carrea, G., Ottolina, G., and Riva, S. (1995) Role of solvents in the control of enzyme selectivity in organic media. Trends Biotechnol. 13, 63–70; erratum: (1995) Trends Biotechnol. 13, 122.
Berglund, P., Holmquist, M., Hult, K., and Högberg, H.-E. (1995) Alcohols as enantio selective inhibitors in a lipase in a lipase catalysed esterification of a chiral acyl donor. Biotechnol. Lett. 17, 55–60.
Berglund, P., Holmquist, M., Hedenström, E., Hult, K., and Högberg, H.-E. (1993) 2-Methylalkanoic acids resolved by esterification catalysed by lipase from Candida rugosa: alcohol chain length and enantioselectivity. Tetrahedron: Asymmetry 4, 1869–1878.
Berglund, P., Vörde, C., and Högberg, H.-E. (1994) Esterification of 2-methylalkanoic acids catalysed by lipase from Candida rugosa: enantioselectivity as a function of water activity and alcohol chain length. Biocatalysis 9, 123–130.
Lundh, M., Smitt, O., and Hedenström, E., (1996) Sex pheromone of pine sawflies: enantioselective lipase catalysed transesterification of erythro-3,-dimethyl-pentadecan-2-ol, diprionol. Tetrahedron: Asymmetry 7, 3277–3284.
Nguyen, B.-V. and Hedenström, E. (1999) Candida rugosa lipase as an enantioselective catalyst in the esterification of methyl branched carboxylic acids: Resolution of rac-3,7-dimethyl-6-octenic acid (citronellic acid). Tetrahedron: Asymmetry 10, 1821–1826.
Halling, P. J. (1992) Salt hydrates for water activity control with biocatalysis in organic media. Biotechnol. Tech. 6, 271–276.
Chen, C.-S., Fujimoto, Y., Girdaukas, G., Sih, C. J. (1982) Quantitative analysis of biochemical kinetic resolutions of enantiomers. J. Am. Chem. Soc. 104, 7294–7299.
Bergström, G., Wassgren, A.-B., Anderbrant, O., Fägerhag, J., Edlund, H., Hedenström, E., et al. (1995) Sex pheromone of the pine sawfly Diprion pini (Hymenoptera: Diprionidae): chemical identification, synthesis and biological activity. Experientia 51, 370–380.
Rakels, J. L. L., Straathof, A. J. J., and Heijnen, J. J. (1993) A simple method to determine the enantiomeric ration in enantioselective biocatalysis. Enzyme Microb. Technol. 15, 1051–1056.
Noyce, D. S. and Denney, D. B. (1950) Steric effects and stereochemistry of lithium aluminium hydride reduction. J. Am. Chem. Soc. 72, 5743–5745.
Sonnet, P. E. (1982) Synthesis of the stereoisomers of the sex pheromone of the southern corn rootworm and lesser tea tortrix. J. Org. Chem. 47, 3793–3796.
Sonnet, P. E. (1987) Kinetic resolutions of aliphatic alcohols with a fungal lipase from Mucormiehei.J. Org. Chem. 52, 3477–3479.
Guanti, G., Narisano, E., Podgorski, T., Thea, S., and Williams, A. (1990) Enzyme catalyzed monohydrolysis of 2-aryl-1, 3-propanediol diacetates. A study of structural effects of the aryl moiety on the enantioselectivity. Tetrahedron 46, 7081–7092.
Bowers, A., Halsall, T. G., Jones, E. R. H., and Lemin, A. J. (1953) The chemistry of the triterpenes and related compounds. Part XVIII. Elucidation of the structure of polyporenic acid C. J. Chem. Soc. 2548–2560.
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Berglund, P., Hedenström, E. (2001). Preparation of 2-, 3-, and 4-Methylcarboxylic Acids and the Corresponding Alcohols of High Enantiopurity by Lipase-Catalyzed Esterification. In: Vulfson, E.N., Halling, P.J., Holland, H.L. (eds) Enzymes in Nonaqueous Solvents. Methods in Biotechnology, vol 15. Humana Press. https://doi.org/10.1385/1-59259-112-4:307
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DOI: https://doi.org/10.1385/1-59259-112-4:307
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