Synthesis and antimicrobial activities of N6-hydroxyagelasine analogs and revision of the structure of ageloximes. Issue 4 (15th February 2019)

• Record Type: Journal Article
• Authors: Paulsen, Britt; Fredriksen, Kim Alex; Petersen, Dirk; Maes, Louis; Matheeussen, An; Naemi, Ali-Oddin; Scheie, Anne Aamdal; Simm, Roger; Ma, Rui; Wan, Baojie; Franzblau, Scott; Gundersen, Lise-Lotte
• Is Part Of: Bioorganic & medicinal chemistry. Volume 27:Issue 4(2019)
• Page Start: 620
• Page End: 629
• Publication Date: 2019-02-15
• Subjects: Agelasine -- Ageloxime -- Antimicrobial activity -- Structure elucidation; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2019.01.002
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: (+)- N 6 -Hydroxyagelasine D, the enantiomer of the proposed structure of (−)-ageloxime D, as well as N 6 -hydroxyagelasine analogs were synthesized by selective N-7 alkylation of N 6 - [ tert -butyl(dimethyl)silyloxy]-9-methyl-9 H -purin-6-amine in order to install the terpenoid side chain, followed by fluoride mediated removal of the TBDMS-protecting group. N 6 -Hydroxyagelasine D and the analog carrying a geranylgeranyl side chain displayed profound antimicrobial activities against several pathogenic bacteria and protozoa and inhibited bacterial biofilm formation. However these compounds were also toxic towards mammalian fibroblast cells (MRC-5). The spectral data of N 6 -hydroxyagelasine D did not match those reported for ageloxime D before. Hence, a revised structure of ageloxime D was proposed. Basic hydrolysis of agelasine D gave (+)- N -[4-amino-6-(methylamino)pyrimidin-5-yl]- N -copalylformamide, a compound with spectral data in full agreement with those reported for (−)-ageloxime D.