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.

Approaches towards the synthesis of 7-halo-1,2-dihydroxyindolizidines (7-halolentiginosines) thwarting Grob fragmentation processes / Vurchio, Carolina; Cordero, Franca M.; Faggi, Cristina; Macchi, Beatrice; Frezza, Caterina; Grelli, Sandro; Brandi, Alberto. - In: TETRAHEDRON. - ISSN 0040-4020. - STAMPA. - 71:(2015), pp. 5806-5813. [10.1016/j.tet.2015.03.108]

Approaches towards the synthesis of 7-halo-1,2-dihydroxyindolizidines (7-halolentiginosines) thwarting Grob fragmentation processes

VURCHIO, CAROLINA;CORDERO, FRANCA MARIA;FAGGI, CRISTINA;BRANDI, ALBERTO
2015

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.
71
5806
5813
Vurchio, Carolina; Cordero, Franca M.; Faggi, Cristina; Macchi, Beatrice; Frezza, Caterina; Grelli, Sandro; Brandi, Alberto
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1006504
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