(1S,2R)-(+)-Norephedrine → Combretastatin A4

HRID 1987962

Reaction equation

HRID 1987962 reaction equation
N([C:9]([O:11][CH:12]([CH3:14])[CH3:13])=O)=NC(OC(C)C)=O.NC1C=CC([CH2:20][OH:21])=CC=1.[CH3:24]C([C@H](NC(OCC1C=CC=CC=1)=O)C(ON1C(=O)CCC1=O)=O)C.N[C@H:50]([C:58]([OH:60])=O)[CH2:51][CH2:52][CH2:53]NC(N)=O.CC(N)C(O)C1C=CC=CC=1.C[C@@H]1O[C@@H](O[C@@H]2C3=C(O)C4C(=O)C5C(=CC=CC=5OC)C(=O)C=4C(O)=C3C[C@@](O)(C(CO)=O)C2)C[C@H](N)[C@@H]1O.CC1[C@@H](OC([C@H](O)[C@@H](NC(C2C=CC=CC=2)=O)C2C=CC=CC=2)=O)C[C@]2(O)C(C)(C)C=1[C@@H](OC(C)=O)C([C@@:117]1(C)[C@H:122]([C@@H]2OC(C2C=CC=CC=2)=O)[C@:121]2([O:163]C(C)=O)[CH2:161][O:162][C@@H:120]2[CH2:119][C@@H:118]1O)=O.CC1C(=O)C2N3[C@@](OC)([C@H](COC(N)=O)C=2C(=O)C=1N)[C@H]1N[C@H]1C3>>[CH3:161][O:162][C:120]1[CH:119]=[CH:118][C:117](/[CH:53]=[CH:52]\[C:51]2[CH:50]=[C:58]([O:60][CH3:24])[C:13]([O:21][CH3:20])=[C:12]([O:11][CH3:9])[CH:14]=2)=[CH:122][C:121]=1[OH:163]

Participants

9

Reactant 8

HCID 4786(1S,2R)-(+)-NorephedrineHCID 5746Mitomycin CHCID 9750CitrullineHCID 31703Doxorubicin2×HCID 36314PaclitaxelHCID 693314-Aminobenzyl alcoholHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 853556L-Valine, N-((phenylmethoxy)carbonyl)-, 2,5-dioxo-1-pyrrolidinyl ester

Product 1

HCID 5351344Combretastatin A4

Procedure

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.

Workup

  1. customCommercially available reagents and solvents were obtained

Sources & evidence

ORD record
ord-121fc07c04634093a3cf6692a5293339
Source dataset
uspto-grants-2009_06
Patent number
US07553816B2

Linked notes

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