HCID 131728605, compound → Glycyl-(4R)-4-hydroxy-L-prolyl-L-glutamic acid

HRID 250797Notes

Reaction equation

HRID 250797 reaction equation
C([C:8](CC1C=CC=CC=1)([C:20]([N:22]1[CH2:38][C@H:37]([OH:39])[CH2:36][C@H:23]1[C:24]([NH:26][C@H:27]([C:33]([O-:35])=[O:34])[CH2:28][CH2:29][C:30]([O-:32])=[O:31])=[O:25])=[O:21])[NH:9]C(OCC1C=CC=CC=1)=O)C1C=CC=CC=1>[Pd].O.CO.CO>[NH2:9][CH2:8][C:20]([N:22]1[CH2:38][C@H:37]([OH:39])[CH2:36][C@H:23]1[C:24]([NH:26][C@H:27]([C:33]([OH:35])=[O:34])[CH2:28][CH2:29][C:30]([OH:32])=[O:31])=[O:25])=[O:21]

Participants

5

Reactant 1

HCID 131728605HCID 131728605, compound

Product 1

HCID 11902976Glycyl-(4R)-4-hydroxy-L-prolyl-L-glutamic acid

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolvent2×HCID 22242641Methanol--water (1/1)Solvent

Procedure

A mixture of protected tripeptide 5 (0.50 g, 0.79 mmol) and 10% palladium on activated carbon (0.08 g, 0.08 mmol) in 20% water/methanol (100 cm3) was stirred under an atmosphere of hydrogen at room temperature for 20 h. The solution was filtered through a Celite™ pad, washed with methanol (60 cm3) and the filtrate evaporated to dryness to form a clear gum. This gum was dissolved in methanol (30 cm3) and refiltered through a Celite™ pad. The solution was evaporated to dryness to form a clear gum. The gum was placed on a vacuum line for 15 min and then triturated with anhydrous diethyl ether to form GHypE (0.20 g, 80%) as a white solid. GHypE was shown to be an 80:20 trans:cis mixture of conformers by 13C NMR analysis (the ratio was estimated from the integration of the signals at 6 70.2 and 68.5, assigned to the Proγ-C of the major and minor conformers respectively): mp 158-160° C.; [α]D −58.1 (c 0.1 in MeOH); δH (300 MHz; D2O) 1.96-2.23 (4H, m, Gluβ-H2, and Proβ-H2), 2.48-2.56 (2H, m, Gluγ-H2), 3.62 (2H, d, J 10.0, Glyα-H2), 3.80 (1H, dd, J 8.8 and 4.9, Gluα-H), 4.08 (1H, dd, J 10.4 and 2.6, Proα-H), 4.30-4.35 (2H, m, Proδ-H2) and 4.63-4.69 (1H, m, Proγ-H); δC (75 MHz, D2O) 29.2 (CH2, Gluβ-C), 31.7 (CH2, Proβ-C), 32.3* (CH2, Proβ-C), 37.6 (CH2, Gluγ-C), 40.0* (CH2, Glyα-C), 41.0 (CH2, Glyα-C), 54.8 (CH2, Proδ-C), 55.3 (CH, Gluα-C), 59.1* (CH, Proα-C), 59.7 (CH, Proα-C), 68.5* (CH, Proγ-C), 70.2 (CH, Proγ-C), 166.4 (quat., Gly-CO), 167.1* (quat., Gly-CO), 173.0* (quat., Pro-CON), 173.4 (quat., Pro-CON), 177.9 (quat., Gluα-CO) and 179.2 (quat., Gluγ-CO); m/z (FAB+) 318.1329 (MH+.C17H20NO5 requires 318.1342).

Workup

  1. filtrationThe solution was filtered through a Celite™ pad
  2. washwashed with methanol (60 cm3)
  3. customthe filtrate evaporated to dryness
  4. customto form a clear gum
  5. customThe solution was evaporated to dryness
  6. customto form a clear gum
  7. waitThe gum was placed on a vacuum line for 15 min
  8. customtriturated with anhydrous diethyl ether
  9. customto form GHypE (0.20 g, 80%) as a white solid
  10. additioncis mixture of conformers by 13C NMR analysis (the ratio

Sources & evidence

ORD record
ord-e2dced610f434f1e927b8ecc2e027c00
Source dataset
uspto-grants-2011_01
Patent number
US07863304B2

Reaction notes

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