Sodium cyanoborohydride → (S)-3-[(2S,3R,4R,5S)-5-(N-((S)-2-amino-3-methylbutyl)-L-leucyl)amino-2,3,4,6-tetrahydroxyhexanoyl]amino-3-phenylpropionic acid

HRID 2230418Notes

Reaction equation

HRID 2230418 reaction equation
C(OC([NH:8][C@H:9]([CH:13]=O)[CH:10]([CH3:12])[CH3:11])=O)(C)(C)C.[OH:15][C@@H:16]([C@H:44]([OH:59])[C@H:45]([OH:58])[C@@H:46]([NH:49][C:50](=[O:57])[C@H:51]([CH2:53][CH:54]([CH3:56])[CH3:55])[NH2:52])[CH2:47][OH:48])[C:17]([NH:19][C@H:20]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH2:21][C:22]([O:24]C(C1C=CC=CC=1)C1C=CC=CC=1)=[O:23])=[O:18].C([BH3-])#N.[Na+]>CO>[NH2:8][C@@H:9]([CH:10]([CH3:12])[CH3:11])[CH2:13][NH:52][C@H:51]([C:50]([NH:49][C@@H:46]([CH2:47][OH:48])[C@@H:45]([OH:58])[C@@H:44]([OH:59])[C@H:16]([OH:15])[C:17]([NH:19][C@H:20]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH2:21][C:22]([OH:24])=[O:23])=[O:18])=[O:57])[CH2:53][CH:54]([CH3:56])[CH3:55]

Participants

5

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 6917569(S)-tert-Butyl (3-methyl-1-oxobutan-2-yl)carbamateHCID 11039599diphenylmethyl (S)-3-[(2S,3R,4R,5S)-2,3,4,6-tetrahydroxy-5-(L-leucyl)aminohexanoyl]amino-3-phenylpropionate

Product 1

HCID 11038822(S)-3-[(2S,3R,4R,5S)-5-(N-((S)-2-amino-3-methylbutyl)-L-leucyl)amino-2,3,4,6-tetrahydroxyhexanoyl]amino-3-phenylpropionic acidYield 10.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-tert-butoxycarbonyl-L-valinal (240 mg) and diphenylmethyl (S)-3-[(2S,3R,4R,5S)-2,3,4,6-tetrahydroxy-5-(L-leucyl)aminohexanoyl]amino-3-phenylpropionate (278 mg) in methanol (10 ml) was added sodium cyanoborohydride (63 mg) at 0° C. and the mixture was stirred at 0° C. for 2 hours and at room temperature for 18 hours. After concentration under reduced pressure, the residue was subjected to flush silica gel column chromatography, followed by elution with ethyl acetate-methanol(20:1). The effective fractions were combined and concentrated under reduced pressure. To the residue was added 4N hydrogen chloride solution in ethyl acetate (10 ml) and the whole was stirred at room temperature for 1 hour. Removal of the organic solvent gave a residue, which was passed through a column of DIAION HP-20SS (Mitsubishi kasei corporation), followed by elution with water-acetonitrile. The effective fractions were combined and concentrated under reduced pressure. The residue was recrystallized from methanol-diethylether to afford the title compound (25 mg).

Workup

  1. concentrationAfter concentration under reduced pressure
  2. customto flush silica gel column chromatography
  3. washfollowed by elution with ethyl acetate-methanol(20:1)
  4. concentrationconcentrated under reduced pressure
  5. additionTo the residue was added 4N hydrogen chloride solution in ethyl acetate (10 ml)
  6. stirringthe whole was stirred at room temperature for 1 hour
  7. customRemoval of the organic solvent
  8. customgave a residue, which
  9. washfollowed by elution with water-acetonitrile
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was recrystallized from methanol-diethylether

Sources & evidence

ORD record
ord-e816bd60e58f4b5fb0ce8df7a873e2ce
Source dataset
uspto-grants-2002_07
Patent number
US06423869B1

Reaction notes

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