Reaktion #324597

ord-baa64055c72c46edb4b6fb547eebad34

Reaktionsgleichung

CC(=O)O[C@H]1C(=O)[C@@]2(C)[C@H]([C@H](OC(=O)c3ccccc3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)c4ccccc4)c4ccccc4)C(C)=C1C3(C)C)[C@]1(OC(C)=O)CO[C@@H]1C[C@@H]2O
Paclitaxel
CC(C)(NCC(O)COc1cccc2[nH]c3ccccc3c12)c1ccc(N=[N+]=[N-])cc1.CC(C)C[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
7
CC(C)(NCC(O)COc1cccc2[nH]c3ccccc3c12)c1ccc(N=[N+]=[N-])cc1.CC(C)C[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
Fmoc-Leu PABC
→
CC(=O)O[C@H]1C(=O)[C@@]2(C)[C@H]([C@H](OC(=O)c3ccccc3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)c4ccccc4)c4ccccc4)C(C)=C1C3(C)C)[C@]1(OC(C)=O)CO[C@@H]1C[C@@H]2O.CC(C)(NCC(O)COc1cccc2[nH]c3ccccc3c12)c1ccc(N=[N+]=[N-])cc1.CC(C)C[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
8
Ausbeute 93.0%
CC(=O)O[C@H]1C(=O)[C@@]2(C)[C@H]([C@H](OC(=O)c3ccccc3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)c4ccccc4)c4ccccc4)C(C)=C1C3(C)C)[C@]1(OC(C)=O)CO[C@@H]1C[C@@H]2O.CC(C)(NCC(O)COc1cccc2[nH]c3ccccc3c12)c1ccc(N=[N+]=[N-])cc1.CC(C)C[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
Fmoc-Leu PABC Paclitaxel
Ausbeute 93.0%

Edukte

CC(=O)O[C@H]1C(=O)[C@@]2(C)[C@H]([C@H](OC(=O)c3ccccc3)[C@]3(O)C[C@H](OC(=O)[C@H](O)[C@@H](NC(=O)c4ccccc4)c4ccccc4)C(C)=C1C3(C)C)[C@]1(OC(C)=O)CO[C@@H]1C[C@@H]2O
Paclitaxel
CC(C)(NCC(O)COc1cccc2[nH]c3ccccc3c12)c1ccc(N=[N+]=[N-])cc1.CC(C)C[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
7
CC(C)(NCC(O)COc1cccc2[nH]c3ccccc3c12)c1ccc(N=[N+]=[N-])cc1.CC(C)C[C@H](NC(=O)OCC1c2ccccc2-c2ccccc21)C(=O)O
Fmoc-Leu PABC

Reagenzien

CN(C)c1ccncc1
4-Dimethylaminopyridine

Lösungsmittel

ClCCl
DCM
ClCCl
DCM

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    Extraktionthe reaction mixture was extracted with NaHCO3, brine
  2. 2
    Trocknendried over sodium sulphate
  3. 3
    SonstigeThe residue was purified on a silica gel column

Vorschrift

Paclitaxel (0.37 g, 0.44 mmol) and 4-Dimethylaminopyridine (DMAP) (0.05 g, 0.44 mmol) were added to a solution of 7 (0.27 g, 0.44 mmol) in anhydrous DCM (15 mL), and the reaction was stirred in the dark at room temperature for 24 hours. Subsequently, DCM (20 mL) was added and the reaction mixture was extracted with NaHCO3, brine and dried over sodium sulphate. The residue was purified on a silica gel column using ethyl acetate/hexane (1:1) to afford 8 (550 mg, 93%) as a white powder. ESI-MS (5 kV, MeOH): m/z (%)=1360.1 (100) [M+Na]+; HPLC (230 nm): >95%.

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08642555B2uspto-grants-2014_02