Hydrochloric Acid → Pepstatin glutamic acid

HRID 2052465Notes

Reaction equation

HRID 2052465 reaction equation
[CH3:1][C@H:2]([NH:17][C:18]([CH2:20][C@H:21]([OH:48])[C@@H:22]([NH:27][C:28]([C@@H:30]([NH:34][C:35]([C@@H:37]([NH:41][C:42]([CH2:44][CH:45]([CH3:47])[CH3:46])=[O:43])[CH:38]([CH3:40])[CH3:39])=[O:36])[CH:31]([CH3:33])[CH3:32])=[O:29])[CH2:23][CH:24]([CH3:26])[CH3:25])=[O:19])[C:3]([NH:5][C@H:6]([C@@H:11]([OH:16])[CH2:12][C:13]([OH:15])=[O:14])[CH2:7][CH:8]([CH3:10])[CH3:9])=[O:4].Cl.[NH2:50][C@H:51]([C:57]([OH:59])=[O:58])[CH2:52][CH2:53][C:54]([OH:56])=[O:55].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>O.C(N(CC)CC)C.CS(C)=O.CN(C)C=O>[CH3:1][C@H:2]([NH:17][C:18]([CH2:20][C@H:21]([OH:48])[C@@H:22]([NH:27][C:28]([C@@H:30]([NH:34][C:35]([C@@H:37]([NH:41][C:42]([CH2:44][CH:45]([CH3:47])[CH3:46])=[O:43])[CH:38]([CH3:40])[CH3:39])=[O:36])[CH:31]([CH3:32])[CH3:33])=[O:29])[CH2:23][CH:24]([CH3:25])[CH3:26])=[O:19])[C:3]([NH:5][C@H:6]([C@@H:11]([OH:16])[CH2:12][C:13]([OH:15])=[O:14])[CH2:7][CH:8]([CH3:9])[CH3:10])=[O:4].[NH2:50][C@H:51]([C:57]([OH:59])=[O:58])[CH2:52][CH2:53][C:54]([OH:56])=[O:55]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 33032L-Glutamic AcidHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 5478883Pepstatin

Product 1

HCID 86736802Pepstatin glutamic acid

Reagents, catalysts & solvents 4

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Into 8 cm3 of a mixture of dimethylformamide and dimethylsulfoxide (3-1 by volume), 130 mg of pepstatin and 120 mg of the hydrochloride of tertiobutyl diester of glutamic acid are added. Then 180 mg of BOP and 45 mg of triethylamine are added. After 72 hours of stirring, 15 cm3 of distilled water are added. The precipitate is drained and washed with 15 cm3 of ethyl ether. The product is redissolved in 30 cm3 of methanol. The insoluble residue is separated by filtration and the filtrate is evaporated. Then 10 cm3 of a mixture of methylene chloride-trifluoroacetic acid (1:1 by volume) are added, then it is allowed to stand for 30 minutes at a temperature close to 20° C. The mixture is concentrated almost to dryness. Ether is then added. The precipitate formed is separated by filtration and then washed with ether. After drying, 130 mg of pepstatin-glutamic acid are obtained whose characteristics are as follows:

Workup

  1. washwashed with 15 cm3 of ethyl ether
  2. dissolutionThe product is redissolved in 30 cm3 of methanol
  3. customThe insoluble residue is separated by filtration
  4. customthe filtrate is evaporated
  5. additionThen 10 cm3 of a mixture of methylene chloride-trifluoroacetic acid (1:1 by volume) are added
  6. waitto stand for 30 minutes at a temperature
  7. customclose to 20° C
  8. concentrationThe mixture is concentrated almost to dryness
  9. additionEther is then added
  10. customThe precipitate formed
  11. customis separated by filtration
  12. washwashed with ether
  13. customAfter drying

Sources & evidence

ORD record
ord-332933489e444da8931f5f60169388c7
Source dataset
uspto-grants-1980_01
Patent number
US04185096

Reaction notes

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