Between alkaloids extracted from Chelidonium majus, we focused our researches on chelidonine , a hexahydrophenanthridine derivative functionalized with a hydroxyl group at C-11 and that is characterized by the presence of two methylenedioxy functions on the aromatic rings. A basic nitrogen and three stereocentres. Studies on the biological activity of this molecule were reported but the mechanism of its action as anticancer agent is not clearly understood. A part Ukrain, a semi-synthetic derivative deriving from chelidonine and tiotepa a lack of extensive SAR studies in the oncogenic field is evinced. This is probably due to the scarce reactivity of this alkaloid, as will be shown in the next chapter that does not allow preparing a large number of compounds. This make chelidonine a “privileged structure from nature” particularly attractive for a chemist also considering the possibility of a total synthesis of analogues of chelidonine not available starting from this alkaloid by semi-synthesis way. For these reasons during my researches I planned - the preparation of a series of derivatives starting from chelidonine - their evaluation as anticancer agents - the total synthesis of hexahydrobenzophenanthridine scaffold aiming to obtain analogues of chelidonine characterized by a different substitution pattern and stereoselectivity. A new synthesis of alfa-amino-beta-hydroxy-isoserine derivatives was also developed.

New synthesis and new derivatives of benzo[c] rhenanthridine alakaloyds / F. Gassa ; tutor: M.L. Gelmi ; coordinatore: C. De Micheli. - : . DIPARTIMENTO DI SCIENZE MOLECOLARI APPLICATE AI BIOSISTEMI, 2009. ((12. ciclo, Anno Accademico 2008/2009.

New synthesis and new derivatives of benzo[c] rhenanthridine alakaloyds

F. Gassa
2009

Abstract

Between alkaloids extracted from Chelidonium majus, we focused our researches on chelidonine , a hexahydrophenanthridine derivative functionalized with a hydroxyl group at C-11 and that is characterized by the presence of two methylenedioxy functions on the aromatic rings. A basic nitrogen and three stereocentres. Studies on the biological activity of this molecule were reported but the mechanism of its action as anticancer agent is not clearly understood. A part Ukrain, a semi-synthetic derivative deriving from chelidonine and tiotepa a lack of extensive SAR studies in the oncogenic field is evinced. This is probably due to the scarce reactivity of this alkaloid, as will be shown in the next chapter that does not allow preparing a large number of compounds. This make chelidonine a “privileged structure from nature” particularly attractive for a chemist also considering the possibility of a total synthesis of analogues of chelidonine not available starting from this alkaloid by semi-synthesis way. For these reasons during my researches I planned - the preparation of a series of derivatives starting from chelidonine - their evaluation as anticancer agents - the total synthesis of hexahydrobenzophenanthridine scaffold aiming to obtain analogues of chelidonine characterized by a different substitution pattern and stereoselectivity. A new synthesis of alfa-amino-beta-hydroxy-isoserine derivatives was also developed.
GELMI, MARIA LUISA
DE MICHELI, CARLO
Settore CHIM/06 - Chimica Organica
New synthesis and new derivatives of benzo[c] rhenanthridine alakaloyds / F. Gassa ; tutor: M.L. Gelmi ; coordinatore: C. De Micheli. - : . DIPARTIMENTO DI SCIENZE MOLECOLARI APPLICATE AI BIOSISTEMI, 2009. ((12. ciclo, Anno Accademico 2008/2009.
Doctoral Thesis
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/153938
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