Approaches towards the synthesis of 7-halo-1, 2-dihydroxyindolizidines (7-halolentiginosines) thwarting Grob fragmentation processes. Issue 35 (2nd September 2015)

• Record Type: Journal Article
• Authors: Vurchio, Carolina; Cordero, Franca M.; Faggi, Cristina; Macchi, Beatrice; Frezza, Caterina; Grelli, Sandro; Brandi, Alberto
• Is Part Of: Tetrahedron. Volume 71:Issue 35(2015)
• Page Start: 5806
• Page End: 5813
• Publication Date: 2015-09-02
• Subjects: Apoptosis -- Azasugar -- Fragmentation reaction -- Halogenation -- Indolizidine; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2015.03.108
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: The synthesis of 7-halo-1, 2-dihydroxyindolizidines (7-halolentiginosines) starting from suitable protected 1, 2, 7-trihydroxyindolizidines (7-hydroxylentiginosines) has been studied. The results indicate a high propensity of the substrates to undergo fragmentation processes under standard halogenations conditions. The analysis of the products allowed an unprecedented full rationalization of Grob fragmentations processes in 7-substituted 1, 2-alkoxyindolizidines. Under optimized Appel reaction conditions 7-chloro- and 7-iodolentiginosines could be exclusively achieved (89–100% yields), whereas fluoruration was extremely sluggish and the 7-fluoro derivative was formed in only 19% through a two-step protocol. Biological assays proved that 7-fluoro- and 7-iodolentiginosines are endowed with proapoptotic activity analogously to (−)-lentiginosine and 7-hydroxylentiginosine. Graphical abstract: