Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Nov 28;18(12):14747-59.
doi: 10.3390/molecules181214747.

OxymaPure/DIC: an efficient reagent for the synthesis of a novel series of 4-[2-(2-acetylaminophenyl)-2-oxo-acetylamino] benzoyl amino acid ester derivatives

Ayman El-Faham  1 , Zainab Al Marhoon, Ahmed Abdel-Megeed, Fernando Albericio
Affiliations

OxymaPure/DIC: an efficient reagent for the synthesis of a novel series of 4-[2-(2-acetylaminophenyl)-2-oxo-acetylamino] benzoyl amino acid ester derivatives

Ayman El-Faham et al. Molecules. .

Abstract

OxymaPure (ethyl 2-cyano-2-(hydroxyimino)acetate) was tested as an additive for use in the carbodiimide (DIC) approach for the synthesis of a novel series of α-ketoamide derivatives (4-[2-(2-acetylaminophenyl)-2-oxo-acetylamino]benzoyl amino acid ester derivatives). OxymaPure showed clear superiority to HOBt/DIC or carbodiimide alone in terms of purity and yield. The title compounds were synthesized via the ring opening of N-acylisatin. First, N-acetylisatin was reacted with 4-aminobenzoic acid under conventional heating as well as microwave irradiation to afford 4-(2-(2-acetamidophenyl)-2-oxoacetamido)benzoic acid. This α-ketoamide was coupled to different amino acid esters using OxymaPure/DIC as a coupling reagent to afford 4-[2-(2-acetylaminophenyl)-2-oxo-acetylamino]benzoyl amino acid ester derivatives in excellent yield and purity. The synthesized compounds were characterized using FT-IR, NMR, and elemental analysis.

PubMed Disclaimer

Figures

Scheme 1
Scheme 1
General mechanism for the reaction of N-acylisatin (1) with amines.
Scheme 2
Scheme 2
Synthesis and reaction of N-acylisatin (1) with 4-aminobenzoic acid (2).
Scheme 3
Scheme 3
Synthesis 4-[2-(2-acetylaminophenyl)-2-oxo-acetylamino]benzoyl amino acid ester derivatives 4a–i.
See this image and copyright information in PMC

References

    1. Li Z., Ortega-Vilain A.C., Patil G.S., Chu D.L., Foreman J.E., Eveleth D.D., Powers J.C. Novel peptidyl α-Keto amide inhibitors of calpains and other cysteine proteases. J. Med. Chem. 1996;39:4089–4098. doi: 10.1021/jm950541c. - DOI - PubMed
    1. James D.A., Koya K., Li H., Liang G., Xia Z., Ying W., Wu Y., Sun L. Indole- and indolizine-glyoxylamides displaying cytotoxicity against multidrug resistant cancer cell lines. Bioorg. Med. Chem. Lett. 2008;18:1784–1787. doi: 10.1016/j.bmcl.2008.02.029. - DOI - PubMed
    1. Montalban A.G., Boman E., Chang C.D., Ceide S.C., Dahl R., Dalesandro D., Delaet N.G.J., Erb E., Ernst J.T., Gibbs A., et al. The design and synthesis of novel α-ketoamide-based p38 MAP kinase inhibitors. J. Bioorg. Med. Chem. Lett. 2008;18:1772–1777. doi: 10.1016/j.bmcl.2008.02.033. - DOI - PubMed
    1. Yu P.-F., Chen H., Wang J., He C.-X., Cao B., Li M., Yang N., Lei Z.Y., Cheng M.-S. Design, synthesis and cytotoxicity of novel podophyllotoxin derivatives. Chem. Pharm. Bull. 2008;56:831–834. doi: 10.1248/cpb.56.831. - DOI - PubMed
    1. Perni R.B., Farmer L.J., Cottrell K.M., Court J.J., Courtney L.F., Deininger D.D., Gates C.A., Harbeson S.L., Kim J.L., Lin C., et al. Inhibitors of hepatitis C virus NS3·4A protease. Part 3: P2 proline variants. Bioorg. Med. Chem. Lett. 2004;14:1939–1942. doi: 10.1016/j.bmcl.2004.01.078. - DOI - PubMed

Publication types