Reaktion #2075144

ord-121fc07c04634093a3cf6692a5293339

Reaktionsgleichung

CO[C@@]12[C@H](COC(N)=O)C3=C(C(=O)C(C)=C(N)C3=O)N1C[C@@H]1N[C@@H]12
Mitomycin C
CC(C)OC(=O)N=NC(=O)OC(C)C
diisopropyl azodicarboxylate
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
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1
Doxorubicin
CC(C)[C@H](NC(=O)OCc1ccccc1)C(=O)ON1C(=O)CCC1=O
Z-val-OSu
NC(=O)NCCC[C@H](N)C(=O)O
L-citrulline
CC(N)C(O)c1ccccc1
(1S, 2R)-(+)-norephedrine
Nc1ccc(CO)cc1
4-aminobenzyl alcohol
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1
Doxorubicin
→
COc1ccc(/C=C\c2cc(OC)c(OC)c(OC)c2)cc1O
combretastatin A-4

Edukte

CO[C@@]12[C@H](COC(N)=O)C3=C(C(=O)C(C)=C(N)C3=O)N1C[C@@H]1N[C@@H]12
Mitomycin C
CC(C)OC(=O)N=NC(=O)OC(C)C
diisopropyl azodicarboxylate
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
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1
Doxorubicin
CC(C)[C@H](NC(=O)OCc1ccccc1)C(=O)ON1C(=O)CCC1=O
Z-val-OSu
NC(=O)NCCC[C@H](N)C(=O)O
L-citrulline
—
Cbz-val-cit-PAB-OH
CC(N)C(O)c1ccccc1
(1S, 2R)-(+)-norephedrine
—
Dipeptide
Nc1ccc(CO)cc1
4-aminobenzyl alcohol
COc1cccc2c1C(=O)c1c(O)c3c(c(O)c1C2=O)C[C@@](O)(C(=O)CO)C[C@@H]3O[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1
Doxorubicin
—
Dipeptide

Reagenzien

Keine

Reaktionsbedingungen

Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    SonstigeCommercially available reagents and solvents were obtained

Vorschrift

Commercially available reagents and solvents were obtained as follows: HPLC-grade solvents, Fisher; anhydrous solvents, Aldrich; diisopropyl azodicarboxylate (DIAD, 95%), Lancaster; 4-aminobenzyl alcohol, Alfa Aesar; Z-val-OSu, Advanced ChemTech; L-citrulline, Novabiochem; (1S, 2R)-(+)-norephedrine and other commercially available reagents, Aldrich. Cbz-val-cit-PAB-OH (1) (Dubowchik, G. M.; Firestone, R. A. Cathepsin B-Sensitive Dipeptide Prodrugs. 1. A Model Study of Structural Requirements for Efficient Release of Doxorubicin. Bioorg. Med. Chem. Letts. 1998, 8, 3341-3346; Dubowchik, G. M.; Mosure, K.; Knipe, J. O.; Firestone, R. A. Cathepsin B-Sensitive Dipeptide Prodrugs. 2. Models of Anticancer Drugs Paclitaxel (Taxol), Mitomycin C and Doxorubicin. Bioorg. Med. Chem. Letts. 1998, 8, 3347-3352) and combretastatin A-4 (VIIIb) (Pettit, G. R.; Singh, S. B.; Boyd, M. R.; Hamel, E.; Pettit, R. K.; Schmidt, J. M.; Hogan, F. Antineoplastic Agents. 291. Isolation and Synthesis of Combretastatin A-4, A-5, and A-6. J. Med. Chem. 1995, 38, 1666-1672) were synthesized as previously described. 1H NMR spectra were recorded on a Varian Gemini 300 MHz spectrophotometer. Flash column chromatography was performed using 230-400 mesh ASTM silica gel from EM Science. Analtech silica gel GHLF plates were used for thin-layer chromatography. HPLC was performed using a Waters Alliance system with a photodiode array detector. Combustion analyses were determined by Quantitative Technologies, Inc., Whitehouse, N.J.

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US07553816B2uspto-grants-2009_06