NADP nicotinamide-adenine-dinucleotide phosphate → 1,1-Dimethylethyl N-[(1S,2R)-3-chloro-2-hydroxy-1-(phenylmethyl)propyl]carbamate

HRID 605463Notes

Reaction equation

HRID 605463 reaction equation
O=C[C@@H]([C@H]([C@@H]([C@@H](CO)O)O)O)O.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.[Cl:61][CH2:62][C:63](=[O:80])[C@@H:64]([NH:72][C:73]([O:75][C:76]([CH3:79])([CH3:78])[CH3:77])=[O:74])[CH2:65][C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1.[OH-].[Na+]>>[Cl:61][CH2:62][C@H:63]([OH:80])[C@@H:64]([NH:72][C:73]([O:75][C:76]([CH3:78])([CH3:77])[CH3:79])=[O:74])[CH2:65][C:66]1[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=1

Participants

5

Reactant 4

HCID 5886NADP nicotinamide-adenine-dinucleotide phosphateHCID 14798Sodium HydroxideHCID 107526(2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal2×HCID 9926241tert-butyl N-((2S)-4-chloro-3-oxo-1-phenylbutan-2-yl)carbamate2×

Product 1

HCID 99441391,1-Dimethylethyl N-[(1S,2R)-3-chloro-2-hydroxy-1-(phenylmethyl)propyl]carbamateYield 99%

Conditions

Temperature
30 °C

Procedure

Glucose dehydrogenase (manufactured by Amano Enzyme) 1250 U, glucose 3 g, NADP 4 mg, (3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanone 0.25 g were added to 22.5 ml of a cell-free extract of E. coli HB101 (pNTOM4) prepared in Example 7, and the mixture was is stirred at 30° C. while adjusting to pH 6.5 by dropwise addition of 5 M sodium hydroxide. (3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanone (0.25 g) was added at 2 hr, 4 hr and 6 hr from the start of the reaction and 1.25 g thereof was added at 8 hr from the start of the reaction, and the mixture was reacted for 31 hr. After completion of the reaction, the reaction mixture was extracted with toluene, desolvated and the extract was analyzed in the same manner as in Example 8. As a result, (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol (yield 99.0%, diastereomeric excess 99.8% d.e.) was obtained.

Workup

  1. extractiona cell-free extract of E
  2. custom(pNTOM4) prepared in Example 7
  3. additionthereof was added at 8 hr from the start of the reaction
  4. customthe mixture was reacted for 31 hr
  5. customAfter completion of the reaction
  6. extractionthe reaction mixture was extracted with toluene

Sources & evidence

ORD record
ord-f68660f9872741859f132ce87fdcb4e5
Source dataset
uspto-grants-2011_03
Patent number
US07915022B2

Reaction notes

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