Unified flexible total synthesis of chlorofusin and artificial Click mimics as antagonists against p53–HDM2 interactions

• Published in: Tetrahedron letters Vol. 55; no. 44; pp. 6055 - 6059
• Main Authors: Qiu, Hai-Bo, Chen, Xin-Ya, Li, Qing, Qian, Wen-Jian, Yu, Shun-Ming, Tang, Gong-Li, Yao, Zhu-Jun
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 29.10.2014; Elsevier
• Subjects: Artificial mimic; Binding; Biological; Chemistry; Chemistry, Organic; Chlorofusin; Chromophores; Flexibility; Inhibitory activity; Natural products; p53–MDM2 interaction; Physical Sciences; Science & Technology; Synthesis (chemistry); Tetrahedrons; Total synthesis; Chlorofusin; Artificial mimic; Total synthesis; p53–MDM2 interaction; Inhibitory activity; CYCLIC PEPTIDE; SOLID-PHASE SYNTHESIS; ASSIGNMENT; CHEMISTRY; p53-MDM2 interaction; INHIBITOR
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2014.09.028

[Display omitted] A practical HPLC-free total synthesis of chlorofusin has been successfully accomplished in this work. The new synthesis showed great flexibility and convenience in generating artificial natural product-like mimics through Click chemistry, and enabled us to further investigate the biological importance of the chromophore and the spiro-aminal functionality of the natural product. The entire skeleton is believed to be essential for satisfactory biological activities of both natural chlorofusin and unnatural mimics. Two artificial Click hybrids were found to exhibit improved inhibitory activity against p53–HDM2 bindings over the natural product.