A facile semi-synthetic approach towards halogen-substituted aminobenzoic acid analogues of platensimycin. Issue 6 (9th February 2017)

• Record Type: Journal Article
• Authors: Qiu, Lin; Tian, Kai; Pan, Jian; Jiang, Lin; Yang, Hu; Zhu, Xiangcheng; Shen, Ben; Duan, Yanwen; Huang, Yong
• Is Part Of: Tetrahedron. Volume 73:Issue 6(2017)
• Page Start: 771
• Page End: 775
• Publication Date: 2017-02-09
• Subjects: Platensimycin -- Platensic acid -- Halogen-substituted aminobenzoate -- Methicillin-resistant Staphylococcus aureus; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2016.12.059
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: Platensimycin (PTM), produced by several strains of Streptomyces platensis, is a promising drug lead for infectious diseases and diabetes. The recent pilot-scale production of PTM from S. platensis SB12026 has set the stage for the facile semi-synthesis of a focused library of PTM analogues. In this study, gram-quantity of platensic acid (PTMA) was prepared by the sulfuric acid-catalyzed ethanolysis of PTM, followed by a mild hydrolysis in aqueous lithium hydroxide. Three PTMA esters were also obtained in near quantitative yields in a single step, suggesting a facile route to make PTMA aliphatic esters. 1-[Bis(dimethylamino)methylene]-1H-1, 2, 3-triazolo[4, 5- b ]pyridinium 3-oxid hexafluorophosphate (HATU)-catalyzed coupling of PTMA and 33 aminobenzoates resulted in the synthesis of 28 substituted aminobenzoate analogues of PTM, among which 26 of them were reported for the first time. Several of the PTM analogues showed weak antibacterial activity against methicillin-resistant Staphylococcus aureus . Our study supported the potential utility to integrate natural product biosynthetic and semi-synthetic approaches for structure diversification. Graphical abstract: