Synthesis of a Sulfonamide Pyruvate Kinase M2 Activator for Cancer Therapy

Title:Synthesis of a Sulfonamide Pyruvate Kinase M2 Activator for Cancer Therapy

Volume: 14 Issue: 4

Author(s): Qun-Zheng Zhang, Dian Zhang, Fei Huang, Cong-Yu Ke, Qing Pan and Xun-Li Zhang*

Affiliation:

• College of Chemistry and Chemical Engineering, Xi`an Shiyou University, Xi`an 710065,China

Keywords: Synthesis, pyruvate kinase M2 (PKM2), activators, sulfonamide, tumor progression, cancer therapy.

Abstract: Background: As evidence suggests a key role played by the low-activity pyruvate kinase M2 (PKM2) in tumor progression it emerges as an attractive target in cancer therapy.

Objective: The aim of the present study was to design and develop a synthetic method for the preparation of a new sulfonamide compound as a potential PKM2 activator.

Method: A seven-step synthesis procedure was carried out. It started with tert-butyl 3-oxoazetidine-1-carboxylate to produce amine compound (2) through nucleophilic addition reaction and deprotection of the Boc-group. By the ring closing reaction of 3-bromobenzene-1,2-diol followed by lithium-halogen exchanges, sulfides compound (4) was obtained which was subsequently oxidized and acylated to produce compound (6). Finally, the reaction of compound (6) with previously prepared amine compound (2) by dehydration resulted in the final sulfonamide product.

Results: The aimed sulfonamide compound was synthesized, namely N-[4-[(3-benzyl-3-hydroxyazetidin-1- yl)carbonyl]phenyl]-2,3-dihydro-1,4-benzodioxine-6-sulfonamide, and the final product was confirmed by spectral analysis with 1H NMR and LC-MS.

Conclusion: A pyruvate kinase M2 (PKM2) activator was successfully prepared through a seven-step synthesis procedure. This compound represents one of the few available small molecule activators of PKM2 which may be further investigated on its biological activities and capacity.

Cite this article as:

Zhang Qun-Zheng , Zhang Dian , Huang Fei , Ke Cong-Yu , Pan Qing and Zhang Xun-Li *, Synthesis of a Sulfonamide Pyruvate Kinase M2 Activator for Cancer Therapy, Current Organic Synthesis 2017; 14 (4) . https://dx.doi.org/10.2174/1570179413666160929142724

DOI https://dx.doi.org/10.2174/1570179413666160929142724	Print ISSN 1570-1794
Publisher Name Bentham Science Publisher	Online ISSN 1875-6271