Hydrochloric Acid → N-Succinyl-S-farnesyl-L-cysteine

HRID 1482462Notes

Reaction equation

HRID 1482462 reaction equation
[CH3:1][C:2]([CH3:22])=[CH:3][CH2:4][CH2:5]/[C:6](/[CH3:21])=[CH:7]/[CH2:8][CH2:9]/[C:10](/[CH3:20])=[CH:11]/[CH2:12][S:13][CH2:14][C@H:15]([NH2:19])[C:16]([OH:18])=[O:17].C([O-])([O-])=O.[K+].[K+].[C:29]1(=[O:35])[O:34][C:32](=[O:33])[CH2:31][CH2:30]1.Cl>C1COCC1>[C:16]([C@@H:15]([NH:19][C:29](=[O:35])[CH2:30][CH2:31][C:32]([OH:34])=[O:33])[CH2:14][S:13][CH2:12]/[CH:11]=[C:10](\[CH3:20])/[CH2:9][CH2:8]/[CH:7]=[C:6](\[CH3:21])/[CH2:5][CH2:4][CH:3]=[C:2]([CH3:22])[CH3:1])([OH:18])=[O:17]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 7922Succinic anhydrideHCID 11430Potassium Carbonate2×HCID 6438372Farnesylcysteine

Product 1

HCID 46207469N-Succinyl-S-farnesyl-L-cysteine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of S-trans, trans-farnesyl-L-cysteine (500 mg, 1.54 mmol) in THF, a first portion of K2CO3 (2 mmol) was added and the resultant solution was cooled to 5° C. with vigorous stirring. To this stirred solution was added succinic anhydride (308 mg, 3.1 mmol) dropwise while maintaining the pH at 9.0-10.0 with another portion of K2CO3 (4 mmol). The mixture was stirred at room temperature for 2 h, HPLC analysis showed completion of the reaction. The pH of the reaction mixture then adjusted to 2.0 by the addition of 2 N HCl solution. The acidic solution was extracted three times with 10 mL of ethyl acetate. The combined organic extract was washed with water, brine and dried over Na2SO4, the solvent was removed on rotary evaporator to afford crude Compound B, which was further purified by preparative HPLC (535 mg, 82%) to yield Compound B. 1H-NMR (500 MHz, CDCl3): δ 1.59 (s, 6H), 1.66 (s, 6H), 2.05 (m, 8H), 2.60 (m, 2H), 2.48 (m, 2H), 2.86 (dd, 1H), 2.94 (dd, 1H), 3.10 (dd, 1H), 3.12 (dd, 1H), 4.68 (dd, 1H), 5.06 (m, 2H), 5.20 (t, 1H). 13C-NMR (125 MHz, CDCl3): δ 16.0, 16.1, 17.7, 25.7, 26.5, 26.7, 29.4, 29.8, 30.5, 32.6, 39.6, 39.7, 52.2, 119.3, 123.8, 124.3, 131.3, 135.4, 140.3, 173.4, 174.2, 176.8; ES-MS: mass calcd for Chemical Formula: C22H35NO5S 425.6. Found (M+Na) m/z 448.

Workup

  1. customcompletion of the reaction
  2. extractionThe acidic solution was extracted three times with 10 mL of ethyl acetate
  3. extractionThe combined organic extract
  4. washwas washed with water, brine
  5. dry with materialdried over Na2SO4
  6. customthe solvent was removed on rotary evaporator
  7. customto afford crude Compound B, which
  8. customwas further purified by preparative HPLC (535 mg, 82%)

Sources & evidence

ORD record
ord-0285b8a3c4ce48878363b1afe1b08a73
Source dataset
uspto-grants-2016_08
Patent number
US09415026B2

Reaction notes

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