The convergent synthesis and anticancer activity of broussonetinines related analogues. (8th November 2017)

• Record Type: Journal Article
• Authors: Jacková, Dominika; Martinková, Miroslava; Gonda, Jozef; Stanková, Kvetoslava; Bago Pilátová, Martina; Herich, Peter; Kožíšek, Jozef
• Is Part Of: Carbohydrate research. Volume 451(2017)
• Page Start: 59
• Page End: 71
• Publication Date: 2017-11-08
• Subjects: Broussonetines -- Broussonetinines -- [3, 3]-Sigmatropic rearrangements -- Oxazolidinones pyrrolidine unit -- Metathesis -- Antiproliferative/cytotoxic activity; Carbohydrates -- Periodicals; Chemistry, Organic -- Periodicals; Biochemistry -- Periodicals; Carbohydrates -- Periodicals; Chimie organique -- Périodiques; Glucides -- Périodiques; Biochemistry; Carbohydrates; Chemistry, Organic; Periodicals; Electronic journals; 507.78
• DOI: 10.1016/j.carres.2017.09.009
• Languages: English
• ISSNs: 0008-6215

Abstract

Abstract: The convergent synthesis of broussonetinines related congeners3 and4 with the simple C13 alkyl side chain and differently configured pyrrolidine skeleton has been achieved. Our approach relied on the [3, 3]-sigmatropic rearrangements of chiral allylic substrates derived fromd -xylose. Cross metathesis of the common oxazolidinone intermediates7 and8 with tridec-1-ene followed by alkylative cyclization completed the construction of both C -alkyl iminosugars. The targeted compounds3 and4 were screened for antiproliferative/cytotoxic activities against multiple cancer cell lines by MTT assay. Compound3 exhibited very good in vitro potency on Caco-2 and Jurkat cell lines with IC50 value of 5.1 μM and 5.8 μM, respectively. Graphical abstract: Highlights: The convergent synthesis of broussonetinines related analogues was accomplished. The cornerstone of this strategy were [3, 3]-heterosigmatropic rearrangements to create the new C-N bond. Crystallographic analysis of a key substructure was performed. Grubbs olefin metathesis chemistry installed the C13 hydrocarbon side chain. Final iminosugars were evaluated for antiproliferative/cytotoxic activities.