Hydrochloric Acid → (35,4r,5s)-6-Azido-5-methoxy-1,3,4-trihydroxyhexan-2-one

HRID 991168

Reaktionsgleichung

Reaktionsgleichung von HRID 991168
C(O[CH:4]([O:12]CC)[C@H:5]([O:10][CH3:11])[CH2:6][N:7]=[N+:8]=[N-:9])C.C(OC(OCC)[C@H](O)CN=[N+]=[N-])C.[CH2:28]([OH:37])[C:29]([CH2:31][O:32]P(O)(O)=O)=[O:30].[OH-].[Na+].C(OP(O)(O)=O)[C@H]1O[C@@](O)(COP(O)(O)=O)[C@@H](O)[C@@H]1O.Cl>O>[N:7]([CH2:6][C@H:5]([O:10][CH3:11])[C@H:4]([OH:12])[C@H:28]([OH:37])[C:29](=[O:30])[CH2:31][OH:32])=[N+:8]=[N-:9]

Komponenten

8

Edukt 6

HCID 313Hydrochloric AcidHCID 668Dihydroxyacetone PhosphateHCID 14798Sodium HydroxideHCID 445557Fructose-1,6-DiphosphateHCID 141838173-Azido-2(r)-hydroxy-propanal diethyl acetalHCID 233928993-Azido-2(r)-methoxy-propanal diethyl acetal

Produkt 1

HCID 131723539(35,4r,5s)-6-Azido-5-methoxy-1,3,4-trihydroxyhexan-2-oneAusbeute 91,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A solution of 3-azido-2(R)-methoxy-propanal diethyl acetal 24 (934 mg, 4.6 mmol) prepared by methylation of 3-azido-2(R)-hydroxy-propanal diethyl acetal obtained enzymatically; von der Osten, C. H.; Barbas, C. F.; Wong, C. H.; Pederson, R. L.; Sinskey, A. J.; Wang, Y. F. J. Am. Chem. Soc. 1989, 111, 3924) was dissolved in water (5 mL) and Dowex 50W-X8 (H+ form, 200-400 mesh) was added until pH <2. The mixture was heated at 50° C. for 8 hours, then the resin was filtered off and washed with a minimum amount of water. A solution of DHAP (262 mM, 7.6 mL, 2 mmol) was added and the mixture was adjusted to pH 6.5 with 6N NaOH. Fructose-1,6-diphosphate aldolase was added (1.4 mL, 500 units; see general section—supra) and the mixture was stirred at room temperature. After 4 h the pH was adjusted to 4.7 with HCl. Acid phosphatase (500 μL, 400 units—see general materials section, supra) was added and the mixture heated at 37° C. The enzyme was precipitated by adding acetone and these residue evaporated and chromatographed on SiO2 (CH2Cl2:MeOH 6:1), to give 400 mg (40%) of (35,4R,5S)-6-azido-5-methoxy-1,3,4-trihydroxyhexan-2-one 26: 1H-NMR (D2O, δ, ppm) 4.48 and 4.35 (1H each, J=19.8 Hz, H1 and H1′); 4.38 (1H, d, J=3 Hz, H3); 3.85 (1H, dd, J=9.2 Hz, 1.9 Hz, H4), 3.7 (1H, dd, J=13.6 Hz, 2.8 Hz, H6); 3.45, (1H, ddd, J=9.2 Hz, 2.8 Hz, 3.7 Hz, H5); 3.33 (3H, s, Me); 3.30 (1H, dd, 13.5 Hz, 3.7 Hz, H6′). 13C-NMR (D2O, δ, ppm): 213.22, 78.55, 74.85, 70.26, 65.98, 57.36, 48.97.

Aufarbeitung

  1. customobtained enzymatically
  2. addition(H+ form, 200-400 mesh) was added until pH <2
  3. filtrationthe resin was filtered off
  4. washwashed with a minimum amount of water
  5. additionAcid phosphatase (500 μL, 400 units—see general materials section, supra) was added
  6. temperaturethe mixture heated at 37° C
  7. customThe enzyme was precipitated
  8. additionby adding acetone
  9. customthese residue evaporated
  10. customchromatographed on SiO2 (CH2Cl2:MeOH 6:1)

Quellen und Nachweise

ORD-Eintrag
ord-c98efaf8ea6d4a2ca6e7c48aad76073a
Quelldatensatz
uspto-grants-2002_10
Patentnummer
US06462193B1

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