WO2010086482A1 - Procédé chimio-enzymatique pour la synthèse de 1-déoxy-d-xylulose - Google Patents

Procédé chimio-enzymatique pour la synthèse de 1-déoxy-d-xylulose Download PDF

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Publication number
WO2010086482A1
WO2010086482A1 PCT/ES2010/070043 ES2010070043W WO2010086482A1 WO 2010086482 A1 WO2010086482 A1 WO 2010086482A1 ES 2010070043 W ES2010070043 W ES 2010070043W WO 2010086482 A1 WO2010086482 A1 WO 2010086482A1
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WO
WIPO (PCT)
Prior art keywords
xylulose
deoxy
fsa
synthesis
enzyme
Prior art date
Application number
PCT/ES2010/070043
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English (en)
Spanish (es)
Inventor
Pedro CLAPÉS SABORIT
Jesús JOGLAR TAMARGO
Alda Lisa Concia
José Antonio CASTILLO EXPÓSITO
Carles LOZANO PÉREZ
Original Assignee
Consejo Superior De Investigaciones Científicas (Csic)
Bioglane S. L. N. E.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Consejo Superior De Investigaciones Científicas (Csic), Bioglane S. L. N. E. filed Critical Consejo Superior De Investigaciones Científicas (Csic)
Publication of WO2010086482A1 publication Critical patent/WO2010086482A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H3/00—Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms
    • C07H3/08—Deoxysugars; Unsaturated sugars; Osones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
    • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
    • C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
    • C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
    • C07C49/04—Saturated compounds containing keto groups bound to acyclic carbon atoms
    • C07C49/17—Saturated compounds containing keto groups bound to acyclic carbon atoms containing hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H3/00—Compounds containing only hydrogen atoms and saccharide radicals having only carbon, hydrogen, and oxygen atoms
    • C07H3/02—Monosaccharides
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/24—Preparation of oxygen-containing organic compounds containing a carbonyl group
    • C12P7/26—Ketones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Definitions

  • the present invention relates to a chemo-enzymatic process for the synthesis of 1-deoxy-D-xylulose. Therefore, the invention falls within the chemical and biotechnological sector.
  • the 1-deoxy-D-xylulose is a pentulose of great importance because it is easily incorporated into the metabolic pathway of the mevalonate (independent of methylerythriol phosphate) for the biosynthesis of isoprenoids, which take place in bacteria and plants.
  • the interest in the biosynthesis of thiamine diphosphate, pyridoxal phosphate and isoprenoids has aroused many expectations in 1-deoxy-D-xylulose for biotechnological uses.
  • 1-deoxy-D-xylulose is particularly valuable in the biotechnological production of terpenes, ketocarotenoids or vitamin B6, among other products of interest.
  • the present invention provides a chemo-enzymatic process useful for the preparation of 1-deoxy-D-xylulose based on the use of the enzyme D-fructose-6-phosphate aldolase (FSA).
  • FSA D-fructose-6-phosphate aldolase
  • a first aspect of the present invention relates to a process for obtaining 1-deoxy-D-xylulose (scheme 1), which comprises the following steps: a) the aldolic addition of benzyloxyacetaldehyde to hydroxyacetone catalyzed by FSA to obtain 5- O-benzyl-1-deoxy-D-xylulose; and b) removal of the benzyl group from the adduct, 5-O-benzyl-1-deoxy-D-xylulose, by catalytic hydrogenolysis to give rise to 1-deoxy-D-xylulose.
  • the catalytic hydrogenolysis of step (b) of the process of the invention consists in the addition of H 2 in the presence of a catalyst, preferably a metal catalyst.
  • a catalyst preferably a metal catalyst.
  • Metallic catalyst refers in this invention to a catalyst whose function in hydrogenation processes is known to a person skilled in the art.
  • this metal catalyst can be selected from the group comprising Pd, Ni, Pt, Ru or Rh. More preferably the metal catalyst is Pd / C.
  • the process of the invention has advantages with respect to the chemo-enzymatic synthesis existing in the state of the art, having a lower number of stages, higher overall yields and a very high stereochemistry. For example:
  • the FSA uses HA in the aldol addition reaction in place of the DHAP thio analogue, eliminating a total of 4 synthetic stages (not counting the preparation of the DHAP thio-analogue and the benzyloxyacetaldehyde) compared to the methodology with DHAP-dependent aldolases, mentioned In the background.
  • the hydrolysis step of the thiophosphate group is eliminated.
  • the FSA is stable at a minimum of 4 0 C for seven months without loss of activity, and also does not use or generate toxic waste, as is the case, for example, in the case of using DHAP-aldolases, when using dihydroxyacetone ( DHA) in the presence of arsenic salts, a highly toxic product and, therefore, dangerous for health and the environment.
  • DHA dihydroxyacetone
  • -FSA has the ability to control the stereochemistry of the aldol addition and, therefore, the configuration of the new stereogenic centers created depends on the enzyme and not on the reagents of the aldol addition.
  • the enzyme D-fructose-6-phosphate aldolase corresponds to the E. coli FSA of SEQ ID NO: 1.
  • the FSA used has been cloned into the E. coli strain MC4100, derived from the E. coli strain K-12 (Schürmann, M .; Sprenger, GAJ Biol. Chem. (2001) 276 11055; Casadaban, MJ (1976) J. Mol. Biol. 104, 541-555) and subsequently purified.
  • Said FSA consists of the wild form of enzyme D-fructose-6-phosphate aldolase that is naturally expressed in E.
  • FSA wild D-fructose-6-phosphate aldolase
  • an analogous amino acid sequence is intended to include any amino acid sequence that can be isolated from a microorganism or by directed mutagenesis and that possesses the aldolic addition capacity between DHA and an acceptor benzyloxyacetaldehyde.
  • an analogous amino acid sequence is substantially homologous to the amino acid sequence discussed above.
  • the expression “substantially homologous” means that the amino acid sequences in question have a degree of identity of at least 30%, preferably of at least 75%, more preferably of, at least 85%, or even more preferably, at least 95%.
  • HA (0.68 g, 9.2 mmol) and FSA aldolase powder (0.113 g, 47 U) were dissolved in 50 mM boric acid / borate buffer pH 7.0 (80 ml_). To this mixture was added benzyloxyacetaldehyde (1.16 g, 7.7 mmol) dissolved in DMF (20 ml_). The reaction mixture was placed on an orbital shaker (120 rpm) at 25 ° C. After 24 hours the conversion reached 99%.
  • Step 2 Deprotection of the benzyl group of 5-O-benzyl-1-deoxy-D-xylulose, by hydrogenolysis with H 2 in the presence of palladium. Obtaining 1-deoxy-D-xylulose.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Enzymes And Modification Thereof (AREA)

Abstract

L'invention concerne un procédé d'obtention de 1-déoxy-D-xylulose qui comprend l'addition aldolique de benzyloxyacétaldéhyde à de l'hydroxyacétone catalysée par FSA pour obtenir de la 5-O-benzyl-1-déoxy- D-xylulose; et l'élimination ultérieure du groupe benzyle de l'adduit, la 5-O-benzyl-1-déoxy- D-xylulose, par hydrogénolyse catalytique pour produire de la 1-déoxy- D-xylulose.
PCT/ES2010/070043 2009-01-29 2010-01-26 Procédé chimio-enzymatique pour la synthèse de 1-déoxy-d-xylulose WO2010086482A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ES200900254A ES2343448B1 (es) 2009-01-29 2009-01-29 Procedimiento quimo-enzimatico para la sintesis de 1-deoxi-d-xilulosa.
ESP200900254 2009-01-29

Publications (1)

Publication Number Publication Date
WO2010086482A1 true WO2010086482A1 (fr) 2010-08-05

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ES (1) ES2343448B1 (fr)
WO (1) WO2010086482A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109207139A (zh) * 2018-10-19 2019-01-15 河南国中铭泰化工科技有限公司 一种非交联植物胶压裂液及其制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6326176B1 (en) * 1997-12-18 2001-12-04 The Scripps Research Institute Aldol condensations by catalytic antibodies
WO2008067997A1 (fr) * 2006-12-05 2008-06-12 Isobionics B.V. Préparation de 4-hydroxy-2,5-diméthyl-2,3-dihydrofuran-3-one

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6326176B1 (en) * 1997-12-18 2001-12-04 The Scripps Research Institute Aldol condensations by catalytic antibodies
WO2008067997A1 (fr) * 2006-12-05 2008-06-12 Isobionics B.V. Préparation de 4-hydroxy-2,5-diméthyl-2,3-dihydrofuran-3-one

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
BLAGG B. S. J. ET AL.: "Synthesis of 1-deoxy-D- xylulose and 1-deoxy-D-xylulose-5-phosphate.", J. ORG. CHEM., vol. 64, 1999, pages 1508 - 1511 *
MEYER O. ET AL.: "Practical synthesis of 1-deoxy-D- xylulose and 1-deoxy-D-xylulose-5-phosphate allowing deuterium labelling.", TETRAHEDRON, vol. 60, 20 October 2004 (2004-10-20), pages 12153 - 12162 *
SCHÜRMANN M. ET AL.: "Fructose-6-phosphate aldolase and 1-deoxy-D-xylulose-5-phosphate synthase from Escherichia coli as tools in enzymatic synthesis of 1-deoxysugars.", JOURNAL OF MOLECULAR CATALYSIS B: ENZYMATIC., vol. 19, no. 20, 2002, pages 247 - 252 *
SCHURMANN M. ET AL.: "Fructose-6-phosphate aldolase is a novthe class I aldolase from Escherichia coli and is related to a novthe group of bacterial transaldolases.", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 276, no. 14, 6 April 2001 (2001-04-06), pages 11055 - 11061 *
SHABAT D. ET AL.: "A short inantioselective synthesis of 1-deoxy-L-xylulose by antibody catalysis.", TETRAHEDRON LETTERS, vol. 40, 1999, pages 1437 - 1440 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109207139A (zh) * 2018-10-19 2019-01-15 河南国中铭泰化工科技有限公司 一种非交联植物胶压裂液及其制备方法

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ES2343448B1 (es) 2011-06-20

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