- PROCESSES FOR THE SYNTHESIS OF 3-HYDROXYGLUTARONITRILE
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There are disclosed high yield and high productivity processes for preparing 3-hydroxyglutaronitrile by reacting allyl cyanide epoxide with a basic aqueous solution of a cyanide source.
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Page/Page column 14-15
(2009/04/25)
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- Nitrilase-catalysed desymmetrisation of 3-hydroxyglutaronitrile: Preparation of a statin side-chain intermediate
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An efficient, scaleable synthesis of ethyl (R)-4-cyano-3-hydroxybutyrate, a potential intermediate in the synthesis of Atorvastatin (Lipitor), has been developed. The three-stage process starts with reaction of low-cost epichlorohydrin with cyanide to give 3-hydroxyglutaronitrile (3-HGN). The second stage utilises a nitrilase-catalysed desymmetrisation of 3-HGN. The nitrilase reaction has been optimized to work at 3 M (330 g/L) substrate concentration, pH 7.5,27 °C. Under these conditions, with an enzyme loading of 6 wt %, 100% conversion and 99% ee product is obtained in 16 h. This material is then esterified to give the target compound, ethyl (R)-4-cyano-3-hydroxybutyrate. The cost-effectiveness of the process is determined by three factors: use of a low-cost starting material, the introduction of the chiral centre by desymmetrisation as opposed to kinetic resolution, and the use of Pfenex Expression Technology to allow a lower-cost supply of biocatalyst.
- Bergeron, Sophie,Chaplin, David A.,Edwards, John H.,Ellis, Brian S. W.,Hill, Catherine L.,Holt-Tiffin, Karen,Knight, Jonathan R.,Mahoney, Thomas,Osborne, Andrew P.,Ruecroft, Graham
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p. 661 - 665
(2012/12/22)
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- An Epoxide Ring-Opening Reaction via Hypervalent Silicate Intermediate: Synthesis of Statine
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The azide- and cyanide-opening reaction of epoxide with TBAF and TMSN 3 in THF or TBAF and TMSCN in MeCN occurred regioselectively to afford β-hydroxy azides and cyanides in good yield. These hypervalent silicates have been shown to be highly effective as nucleophilic azide and cyanide donors under mild conditions. This methodology has been applied to the preparation of statine.
- Konno, Hiroyuki,Toshiro, Emi,Hinoda, Naoyuki
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p. 2161 - 2164
(2007/10/03)
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- PROCESSES FOR MAKING (R)-ETHYL 4-CYANO-3-HYDROXYBUTYRIC ACID
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The invention provides novel processes for making ethyl-4-cyano-3-hydroxybutyrate, e.g., (R)-ethyl 4-cyano-3-hydroxybutyric acid, and 4-cyano-3-hydroxybutyric acid. The invention provides protocols for making and 4-cyano-3-hydroxybutyric acid and ethyl-4-cyano-3-hydroxybutyrate by whole cell processes, cell lysate processes, "one pot processes" and "multi-pot" processes using a variety of parameters.
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- A stereodivergent approach to substituted 4-hydroxypiperidines
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A stereodivergent route toward both diastereomeric forms of functionalized 4-hydroxypiperidines has been successfully developed. This route involves biocatalytic generation of the enantiopure starting materials followed by functionalization via N-acyliminium ion-mediated CC-bond formation.
- Vink, Mandy K. S.,Schortinghuis, Christien A.,Luten, Jordy,Van Maarseveen, Jan H.,Schoemaker, Hans E.,Hiemstra, Henk,Rutjes, Floris P. J. T.
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p. 7869 - 7871
(2007/10/03)
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- Nitrile hydratase enzymes in organic synthesis: Enantioselective synthesis of the lactone moiety of the mevinic acids
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(R)-4-Hydroxy-5-cyanopentene (-)-9, a known precursor of the protected lactone moiety of the mevinic acids 1, has been prepared in 9 steps from (S)-3-(benzyloxy)-4-cyanobutanoic acid 5 (88% e.e.) which was obtained by the asymmetric 2 step hydrolysis of 3-benzyloxyglutaronitrile 4 involving the successive activity of a nitrile hydratase and an amidase enzyme.
- Maddrell, Samuel J.,Turner, Nicholas J.,Kerridge, Alison,Willetts, Andrew J.,Crosby, John
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p. 6001 - 6004
(2007/10/03)
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- A new method for the preparation of β-hydroxy nitriles; Transformation of 3-bromo-2-isoxazolines to β-hydroxy nitriles by treatment of alkanethiolates
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3-Bromo-2-isoxazolines are transformed to β-hydroxy nitriles in good yields by treatment with alkanethiolates under a very mild condition.
- Min Hyo Seo,Youn Young Lee,Yang Mo Goo
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p. 1433 - 1439
(2007/10/02)
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- A 13C and 1H NMR Study of the Geometries of the 1,3-Dicyanoallyl Anion: Thermal and Photochemical Interconversion
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Glutacononitrile (1,3-dicyanopropene) (2) was converted to its anion (1) by treatment with sodium hydride in tetrahydrofuran.Both 13C and 1H NMR showed that the sodium salt of 1 in THF existed in three slowly interconverting geometries (U, W and S).These geometries were present in similar amounts but the relative amounts of each proved to be concentration dependent.Irradiation of a 0.01 M solution of 1 at -80 deg C led to the conversion of a mixture of the U, W and S forms of 1 to only the W and S forms.Upon warming to 0 deg C equilibrium was re-established with a half-life of approximately 8 h.
- Boate, D. R.,Hunter, D. H.
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p. 167 - 170
(2007/10/02)
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