NADP nicotinamide-adenine-dinucleotide phosphate → HCID 59619444, compound

HRID 1367549Notes

Reaction equation

HRID 1367549 reaction equation
[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][C:9](=[O:11])[CH2:8][C@H:7]1[C:12]([OH:14])=[O:13])=[O:5])[CH3:2].C1N(CCS(O)(=O)=O)CCOC1.O=C[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O.[Cl-].[Mg+2].[Cl-].C1C=[N+]([C@@H]2O[C@H](COP(OP(OC[C@H]3O[C@@H](N4C5N=CN=C(N)C=5N=C4)[C@H](OP(O)(O)=O)[C@@H]3O)(O)=O)(O)=O)[C@@H](O)[C@H]2O)C=C(C(N)=O)C=1.[OH-].[Na+]>C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C@@H:6]1[CH2:10][C@H:9]([OH:11])[CH2:8][C@H:7]1[C:12]([OH:14])=[O:13])=[O:5])[CH3:2]

Participants

8

Reactant 6

HCID 5886NADP nicotinamide-adenine-dinucleotide phosphateHCID 14798Sodium HydroxideHCID 781654-Morpholineethanesulfonic acidHCID 107526(2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal2×HCID 5360315Magnesium ChlorideHCID 59619308HCID 59619308, compound

Product 1

HCID 59619444HCID 59619444, compoundYield 67.7%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of (1R,2R)-4-oxo-cyclopentane-1,2-dicarboxylic acid monoethyl ester (example 1, step 1, 6.0 g) in an aqueous buffer (600 mL, 30 mM; 2-(N-morpholino)ethanesulfonic acid; 0.5 M D-glucose [10 equ.]; 2 mM Magnesium chloride) was adjusted to pH 6.4 at 35° C. Under stirring the reduction was started by the addition of the cofactor NADP (120 mg), the cofactor regeneration enzyme-glucose dehydrogenase (120 mg GDH 102 [Codexis]) and the reductase (1.2 g KRED-NADP-174 [Codexis]). During the 69 h reaction time at 35° C. the pH was kept at pH 6.5 by the addition of 1M NaOH. Afterwards the enzymes were denatured by adjusting to pH 2, adding a total of 300 mL ethyl acetate and a total of 60 g filter aid—Dicalite under stirring of at least 1.5 h. After filtration, two further extractions with 200 mL ethyl acetate, treatment of the combined organic phases with magnesium sulfate, evaporation and drying for 4 h on a high vacuum, 4.1 g of the title compound was isolated. MS: 201.07 (M−H)−; chiral GC: d.r.: 1.4:97.3:1.4: 0.0 [BGB-172 (BGB Analytik AG), 30 m*0.25 mm; 0.25 μm; H2; 2° C./min, 100° C. to 200° C.]. An additional extraction of the aqueous phase with further 200 mL ethyl acetate yielded after treatment with magnesium sulfate, evaporation and drying for 4 h on a high vacuum in 1.62 g of the title compound. MS: 201.07 (M−H)−; chiral GC: d.r.: 1.3:96.3:1.6:0.4. The summing up gave a total yield of 5.72 g (93.9%).

Workup

  1. customwas adjusted to pH 6.4 at 35° C
  2. customDuring the 69 h reaction time at 35° C. the pH
  3. filtrationa total of 60 g filter aid—Dicalite
  4. stirringunder stirring of at least 1.5 h
  5. filtrationAfter filtration, two further extractions with 200 mL ethyl acetate, treatment of the combined organic phases
  6. customwith magnesium sulfate, evaporation
  7. customdrying for 4 h on a high vacuum

Sources & evidence

ORD record
ord-886a50ba29b2458eae5bd520ce8ecccd
Source dataset
uspto-grants-2011_02
Patent number
US07893099B2

Reaction notes

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