Water → L-Pyroglutamyl-L-methionyl-L-alanyl-L-valyl-L-lysine

HRID 1732525Notes

Reaction equation

HRID 1732525 reaction equation
C([O:8][C:9](=[O:63])[C@H:10]([CH2:48][CH2:49][CH2:50][CH2:51][NH:52]C(OCC1C=CC=CC=1)=O)[NH:11][C:12](=[O:47])[C@H:13]([CH:44]([CH3:46])[CH3:45])[NH:14][C:15](=[O:43])[C@H:16]([CH3:42])[NH:17][C:18](=[O:41])[C@H:19]([CH2:37][CH2:38][S:39][CH3:40])[NH:20][C:21](=[O:36])[C@H:22]([CH2:31][CH2:32]C(=O)N)[NH:23][C:24]([O:26]C(C)(C)C)=O)C1C=CC=CC=1.O.CCN(C(C)C)C(C)C.[SH3+]>CN(C=O)C.CC(O)=O.[Pd].[O-]S([O-])(=O)=O.[Ba+2]>[NH:23]1[C:24](=[O:26])[CH2:32][CH2:31][C@H:22]1[C:21]([NH:20][C@H:19]([C:18]([NH:17][C@H:16]([C:15]([NH:14][C@H:13]([C:12]([NH:11][C@H:10]([C:9]([OH:8])=[O:63])[CH2:48][CH2:49][CH2:50][CH2:51][NH2:52])=[O:47])[CH:44]([CH3:45])[CH3:46])=[O:43])[CH3:42])=[O:41])[CH2:37][CH2:38][S:39][CH3:40])=[O:36]

Participants

8

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 3015009SulfoniumHCID 86737376t-Butyloxycarbonyl-L-glutaminyl-L-methionyl-L-alanyl-L-valyl-Nepsilon-benzyloxycarbonyl-L-lysine benzyl ester

Product 1

HCID 22813237L-Pyroglutamyl-L-methionyl-L-alanyl-L-valyl-L-lysine

Reagents, catalysts & solvents 3

HCID 16218511Pd barium sulfateCatalystHCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

A sample of the protected 5-peptide XXIII (0.50 g, 0.55 mmole) was dissolved in DMF (60 ml), H2O (6 ml), DIEA (6 ml) and 10% Pd/BaSO4 (0.10 g) were added and the mixture hydrogenated for 8 hr. On tlc a single spot (RfC, 0.45; RfL, 0.75) was observed. The black solution was filtered on a layer of Celite, the latter washed with DMF and the filtrates evaporated in vacuo to dryness. The residue was dissolved in TFA (20 ml) containing acetyl-DL-methionine n-butyl ester (1.0 g) and kept at room temperature for 1/2 hr. The TFA was removed in vacuo and the residue dissolved in a mixture of EtOAc (20 ml) and H2O (20 ml). The aqueous layer was extracted twice with EtOAc (20 ml each), filtered and lyophilized to give a white powder, 0.40 g. In system C the spot remained near the origin; RfM, 0.45. Trace amounts of impurities, probably the pyroglutamyl derivative and the sulfonium salt could also be detected. A sample (0.10 g) was dissolved in AcOH (ca 2 ml) and heated to boiling for 3 min. After cooling the product was precipitated with ether (20 ml). The pyroglutamyl derivative was collected, washed with ether: 80 mg; m.p. 238°-242° C.; RfC, 0.10; RfM, 0.60. Glu, 0.98; Ala, 0.99; Val, 1.01; Met, 0.96.

Workup

  1. filtrationThe black solution was filtered on a layer of Celite
  2. washthe latter washed with DMF
  3. customthe filtrates evaporated in vacuo to dryness
  4. dissolutionThe residue was dissolved in TFA (20 ml)
  5. additioncontaining acetyl-DL-methionine n-butyl ester (1.0 g)
  6. waitkept at room temperature for 1/2 hr
  7. customThe TFA was removed in vacuo
  8. dissolutionthe residue dissolved in a mixture of EtOAc (20 ml) and H2O (20 ml)
  9. extractionThe aqueous layer was extracted twice with EtOAc (20 ml each)
  10. filtrationfiltered
  11. customto give a white powder, 0.40 g
  12. temperatureheated
  13. waitto boiling for 3 min
  14. temperatureAfter cooling the product
  15. customwas precipitated with ether (20 ml)
  16. customThe pyroglutamyl derivative was collected
  17. washwashed with ether

Sources & evidence

ORD record
ord-0dca89cec27c47f1a8364f662a2a6eb1
Source dataset
uspto-grants-1980_12
Patent number
US04237046

Reaction notes

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