Hydrochloric Acid → 4-((R)-1-carboxy-2-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienylthio)ethylamino)-2-methylene-4-oxobutanoic acid

HRID 388153

Reaktionsgleichung

Reaktionsgleichung von HRID 388153
[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+].[CH2:29]=[C:30]1[CH2:34][C:33](=[O:35])[O:32][C:31]1=[O:36].Cl>C1COCC1>[C:16]([C@@H:15]([NH:19][C:33](=[O:35])[CH2:34][C:30](=[CH2:29])[C:31]([OH:36])=[O:32])[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]

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 11430Potassium Carbonate2×HCID 75110Itaconic AnhydrideHCID 6438372Farnesylcysteine

Produkt 1

HCID 462074754-((R)-1-carboxy-2-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienylthio)ethylamino)-2-methylene-4-oxobutanoic acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

S-trans, trans-Farnesyl-L-cysteine (500 mg, 1.54 mmol) was dissolved in mixture of THF and a first portion of K2CO3 (3 mmol) and the resulting solution was cooled to 5° C. with vigorous stirring. To this stirred solution was added 3-methylenedihydro-2,5-furandione (302 mg, 3.07 mmol) portionwise while maintaining the pH at 9.0-10.0 with another portion of K2CO3 (3 mmol). The mixture was stirred at room temperature for 3 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 15 mL of ethyl acetate. The combined organic extract was washed with water, brine and dried over Na2SO4, the solvent was removed under reduced pressure to afford crude Compound F, which was further purified by preparative HPLC (552 mg, 82%) to yield Compound F. 1H-NMR (500 MHz, CDCl3): δ 1.59 (s, 6H), 1.67 (s, 3H), 1.68 (s, 3H), 2.05 (m, 8H), 2.88 (dd, J=6.5, 14.0, 1H), 2.95 (dd, J=6.5, 14.0, 1H), 3.17-3.15 (m, 2H), 3.36 (d, J=14 Hz, 1H), 4.77 (dd, J=6, 12.5 Hz, 1H), 5.09 (bt, 2H), 5.22 (t, J=7.5 Hz, 1H), 5.93 (s, 1H), 6.46 (s, 1H). 13C-NMR (125 MHz, CDCl3): δ 16.0, 16.2, 17.7, 25.7, 26.7, 29.9, 32.8, 39.6, 39.7, 40.2, 52.0, 119.4, 123.7, 131.3, 132.0, 135.4, 140.3, 170.3, 171.5, 176.0; ES-MS: mass calcd for Chemical Formula: C23H35NO5S 437.6. Found (M+Na) m/z 446.

Aufarbeitung

  1. customcompletion of the reaction
  2. extractionThe acidic solution was extracted three times with 15 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 under reduced pressure
  7. customto afford crude Compound F, which
  8. customwas further purified by preparative HPLC (552 mg, 82%)

Quellen und Nachweise

ORD-Eintrag
ord-ea314902d4824602afd3aaaa46286da4
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08372884B2

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