Diisopropylethylamine → (6S,9R,13E,17E)-6-(hydroxymethyl)-2,2,14,18,22-pentamethyl-4,7-dioxo-3-oxa-11-thia-5,8-diazatricosa-13,17,21-triene-9-carboxylic acid

HRID 388156

Reaktionsgleichung

Reaktionsgleichung von HRID 388156
[C:1]([NH:8][C@H:9]([C:12]([OH:14])=O)[CH2:10][OH:11])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C[C@@H](O)[C@@H]1NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC2C=CC=CC=2)NC(=O)[C@H](CCN)NC(=O)[C@@H](NC([C@@H](N)CCN)=O)CCNC1=O.OS(O)(=O)=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[CH3:114][C:115]([CH3:135])=[CH:116][CH2:117][CH2:118]/[C:119](/[CH3:134])=[CH:120]/[CH2:121][CH2:122]/[C:123](/[CH3:133])=[CH:124]/[CH2:125][S:126][CH2:127][C@H:128]([NH2:132])[C:129]([OH:131])=[O:130]>C(Cl)Cl>[OH:11][CH2:10][C@@H:9]([C:12](=[O:14])[NH:132][C@H:128]([C:129]([OH:131])=[O:130])[CH2:127][S:126][CH2:125]/[CH:124]=[C:123](\[CH3:133])/[CH2:122][CH2:121]/[CH:120]=[C:119](\[CH3:134])/[CH2:118][CH2:117][CH:116]=[C:115]([CH3:135])[CH3:114])[NH:8][C:1](=[O:2])[O:3][C:4]([CH3:5])([CH3:6])[CH3:7]

Komponenten

7

Edukt 5

HCID 81531DiisopropylethylamineHCID 98766N-[tert-butoxycarbonyl]-L-serineHCID 197465Dab-cyclo(dab-dab-phe-leu-dab-dab-thr) sulfate saltHCID 6438372FarnesylcysteineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Produkt 1

HCID 46208614(6S,9R,13E,17E)-6-(hydroxymethyl)-2,2,14,18,22-pentamethyl-4,7-dioxo-3-oxa-11-thia-5,8-diazatricosa-13,17,21-triene-9-carboxylic acid

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

In a 100 mL round bottom flask, N-Boc-L-serine (1.0 mmol), coupling reagent (520 mg of PBOP or 380 mg of HATU, 1 mmol) and N,N-diisopropyl-ethyl-amine (650 mg, 5 mmol) were mixed in CH2Cl2 (10 mL). The reaction mixture was stirred at room temperature for 30 minutes. S-trans, trans-farnesyl-L-cysteine (325 mg, 1 mmol) was added to the reaction mixture. The reaction mixture was stirred at room temperature overnight and the CH2Cl2 was removed by rotary evaporation. The remaining residue was dissolved in ethyl acetate (50 mL). The resulting organic solution was washed with an NH4Cl saturated solution (50 mL), dried over Na2SO4, and concentrated to afford a crude mixture. The crude mixture was purified by preparative HPLC (51 mg, 10%) to yield Compound N-55. 1H-NMR (500 MHz, CD3OD): δ 1.47 (s, 9H), 1.62 (bs, 6H), 1.69 (s, 3H), 1.71 (s, 3H), 1.99 (t, J=7 Hz, 2H), 2.05-2.22 (m, 6H), 2.81 (dd, J=7.5, 14 Hz, 1H), 3.01 (dd, J=4, 14.5 Hz, 1H), 3.17 (dd, J=7, 13 Hz, 1H), 3.27 (dd, J=8, 12.5 Hz, 1H), 3.33 (bs, 2H), 3.74-3.80 (m, 2H), 4.22 (t, J=5 Hz, 1H), 4.63 (dd, J=5, 7.5 Hz, 1H), 5.11 (m, 2H), 5.23 (t, J=7.5 Hz, 1H). 13C-NMR (125 MHz, CDCl3): δ 16.2, 16.3, 17.8, 26.0, 27.4, 27.8, 28.7, 30.4, 33.6, 40.8, 40.9, 53.3, 58.0, 59.6, 63.4, 80.9, 121.6, 125.2, 125.5, 132.1, 136.3, 140.6, 157.8, 173.0, 173.8; ES-MS: mass calcd for Chemical Formula: C26H44N2O6S 512.7. Found (M+Na) m/z 535.4.

Aufarbeitung

  1. stirringThe reaction mixture was stirred at room temperature overnight
  2. customthe CH2Cl2 was removed by rotary evaporation
  3. dissolutionThe remaining residue was dissolved in ethyl acetate (50 mL)
  4. washThe resulting organic solution was washed with an NH4Cl saturated solution (50 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto afford a crude mixture
  8. customThe crude mixture was purified by preparative HPLC (51 mg, 10%)

Quellen und Nachweise

ORD-Eintrag
ord-b8d4c102ae7c4c5fa36a7a467c9d1a74
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08372884B2

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