Details
| Originalsprache | Englisch |
|---|---|
| Seiten (von - bis) | 3173-3177 |
| Seitenumfang | 5 |
| Fachzeitschrift | Organic and Biomolecular Chemistry |
| Jahrgang | 1 |
| Ausgabenummer | 18 |
| Publikationsstatus | Veröffentlicht - 21 Sept. 2003 |
| Extern publiziert | Ja |
Abstract
1-Deoxy-D-xylulose-5-phosphate (DXP) is a key intermediate in the non-mevalonate pathway to terpenoids in bacteria, and it is the substrate for the enzyme 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXP-R). In order to study the mechanism of DXP-R, we required a flexible synthesis of the substrate which would allow the incorporation of isotopic labels, and the variation of the two stereocentres. Thus 1,4-dihydroxypent-2-yne was selectively reduced to give the E-olefin, and selective phosphorylation of the primary alcohol followed by oxidation of the secondary alcohol gave a substrate suitable for dihydroxylation. Dihydroxylation using stoichiometric OsO4 in the presence of chiral ligands gave protected DXP in high ee. Final hydrogenolysis gave DXP in quantitative yield and high purity. DXP-R was produced by rapid cloning of the dxr gene from Escherichia coli through controlled expression and ion exchange chromatography. The synthetic DXP was fully active in enzyme assays catalysed by recombinant DXP-R.
ASJC Scopus Sachgebiete
- Biochemie, Genetik und Molekularbiologie (insg.)
- Biochemie
- Chemie (insg.)
- Physikalische und Theoretische Chemie
- Chemie (insg.)
- Organische Chemie
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in: Organic and Biomolecular Chemistry, Jahrgang 1, Nr. 18, 21.09.2003, S. 3173-3177.
Publikation: Beitrag in Fachzeitschrift › Artikel › Forschung › Peer-Review
}
TY - JOUR
T1 - Rapid and flexible synthesis of 1-deoxy-D-xylulose-5-phosphate, the substrate for 1-deoxy-D-xylulose-5-phosphate reductoisomerase
AU - Cox, Russell J.
AU - De Andrés-Gómez, Ana
AU - Godfrey, Christopher R.A.
PY - 2003/9/21
Y1 - 2003/9/21
N2 - 1-Deoxy-D-xylulose-5-phosphate (DXP) is a key intermediate in the non-mevalonate pathway to terpenoids in bacteria, and it is the substrate for the enzyme 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXP-R). In order to study the mechanism of DXP-R, we required a flexible synthesis of the substrate which would allow the incorporation of isotopic labels, and the variation of the two stereocentres. Thus 1,4-dihydroxypent-2-yne was selectively reduced to give the E-olefin, and selective phosphorylation of the primary alcohol followed by oxidation of the secondary alcohol gave a substrate suitable for dihydroxylation. Dihydroxylation using stoichiometric OsO4 in the presence of chiral ligands gave protected DXP in high ee. Final hydrogenolysis gave DXP in quantitative yield and high purity. DXP-R was produced by rapid cloning of the dxr gene from Escherichia coli through controlled expression and ion exchange chromatography. The synthetic DXP was fully active in enzyme assays catalysed by recombinant DXP-R.
AB - 1-Deoxy-D-xylulose-5-phosphate (DXP) is a key intermediate in the non-mevalonate pathway to terpenoids in bacteria, and it is the substrate for the enzyme 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXP-R). In order to study the mechanism of DXP-R, we required a flexible synthesis of the substrate which would allow the incorporation of isotopic labels, and the variation of the two stereocentres. Thus 1,4-dihydroxypent-2-yne was selectively reduced to give the E-olefin, and selective phosphorylation of the primary alcohol followed by oxidation of the secondary alcohol gave a substrate suitable for dihydroxylation. Dihydroxylation using stoichiometric OsO4 in the presence of chiral ligands gave protected DXP in high ee. Final hydrogenolysis gave DXP in quantitative yield and high purity. DXP-R was produced by rapid cloning of the dxr gene from Escherichia coli through controlled expression and ion exchange chromatography. The synthetic DXP was fully active in enzyme assays catalysed by recombinant DXP-R.
UR - http://www.scopus.com/inward/record.url?scp=0141526230&partnerID=8YFLogxK
U2 - 10.1039/b307314a
DO - 10.1039/b307314a
M3 - Article
C2 - 14527148
AN - SCOPUS:0141526230
VL - 1
SP - 3173
EP - 3177
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
SN - 1477-0520
IS - 18
ER -