NADP nicotinamide-adenine-dinucleotide phosphate → HCID 66918856, compound

HRID 1367512Notes

Reaction equation

HRID 1367512 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]([N:14]1[CH2:17][C:16]([F:19])([F:18])[CH2:15]1)=[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+]>>[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]([N:14]1[CH2:15][C:16]([F:19])([F:18])[CH2:17]1)=[O:13])=[O:5])[CH3:2]

Participants

7

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 66918650HCID 66918650, compound

Product 1

HCID 66918856HCID 66918856, compoundYield 95.4%

Procedure

A suspension of 2.3 g (1R,2R)-2-(3,3-Difluoro-azetidine-1-carbonyl)-4-oxo-cyclopentanecarboxylic acid ethyl ester in 50.6 mL aqueous buffer (30 mM 2-(N-morpholino)ethanesulfonic acid; 0.5 M D-glucose [2.7 equ.]; 2 mM Magnesium chloride) was adjusted to pH 6.5 at 35° C. Under stirring the reduction was started by the addition of the cofactor NADP (23 mg [0.03 equ.]), the cofactor regeneration enzyme-glucose dehydrogenase (23 mg GDH 102 [Codexis]) and the reductase (23 mg KRED-NADP-131 [Codexis]). During the 17 h reaction time at 35° C. the pH was kept at pH 6.5 by the addition of 8.25 mL 1M NaOH. Under stirring the mixture was mixed with 1.5 g filter aid—Dicalite—and 30 mL ethyl acetate for at least 10 min. at room temperature. Subsequently the filter aid was washed with 30 ml water and 70 mL ethyl acetate. Afterwards the filter aid was discarded. The filtrate was extracted trice with 100 mL ethyl acetate. Treatment of the combined organic phases with sodium sulfate, evaporation and drying over night on a high vacuum yielded in 2.21 g of the title compound. MS: 278.2 (M+H)+; chiral GC: ee 99.5% [BGB-172, 60 m; H2; 10° C./min, 100° C. to 180° C.; 1° C./min, 180° C. to 230° C.].

Workup

  1. customwas adjusted to pH 6.5 at 35° C
  2. customDuring the 17 h reaction time at 35° C. the pH
  3. stirringUnder stirring the mixture
  4. additionwas mixed with 1.5 g
  5. filtrationfilter aid—Dicalite—and 30 mL ethyl acetate for at least 10 min. at room temperature
  6. washSubsequently the filter aid was washed with 30 ml water and 70 mL ethyl acetate
  7. extractionThe filtrate was extracted trice with 100 mL ethyl acetate
  8. customTreatment of the combined organic phases with sodium sulfate, evaporation
  9. customdrying over night on a high vacuum

Sources & evidence

ORD record
ord-5362982c9eab4f588f9abcfd3214868a
Source dataset
uspto-grants-2011_02
Patent number
US07893099B2

Reaction notes

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