Lamellarins are a group of marine alkaloids. The first four members of this group, Lamellarins A-D, were originally isolated in 1985 by Faulkner and co-workers from six specimens of the marine mollusc Lamellaria sp. Since then, a family of about 42 structurally related lamellarins has been isolated from molluscs, ascidians and sponge species. Lamellarins have attracted considerable attention owing to their antitumor activity and lamellarin D is one of the most cytotoxic compounds in the series. This compound exhibits potent anticancer activity at nanomolar concentration and is a potent inhibitor of the enzyme topoisomerase I (topoI). Although several lamellarin derivatives show potent anticancer potency in vitro, they suffer from several drawbacks that result from low water solubility and relatively labile nature of the lactone ring under basic conditions. In this work the pyrrolo[2,1-a]isoquinoline core was replaced by a beta-carbolin-1-one moiety and the labile lactone ring was substituted with a 3,4-dihydro-2H-[1,3]oxazine (2). The analogues were synthesized by an intramolecular Friedel-Crafts cyclization of appropriate indole-2-carboxilic acid beta-oxoamides, obtained by coupling 2-indole carboxylic acids and substituted 2-amino-1,2-diphenyl-ethanones. Ring-closure to give the tetracyclic core was achieved using diiodomethane under basic conditions.

Design and syntheis of new Lamellarin D analogues / S. Cananzi, S. Dallavalle, L. Merlini, R. Cincinelli, L. Musso, R. Nannei. ((Intervento presentato al 12. convegno Tetrahedron Symosyum-Challenges in Organic and Biooranic Chemistry tenutosi a Sitges (Spain) nel 2011.

Design and syntheis of new Lamellarin D analogues

S. Cananzi
Primo
;
S. Dallavalle
Secondo
;
L. Merlini;R. Cincinelli;L. Musso
Penultimo
;
R. Nannei
Ultimo
2011-06-22

Abstract

Lamellarins are a group of marine alkaloids. The first four members of this group, Lamellarins A-D, were originally isolated in 1985 by Faulkner and co-workers from six specimens of the marine mollusc Lamellaria sp. Since then, a family of about 42 structurally related lamellarins has been isolated from molluscs, ascidians and sponge species. Lamellarins have attracted considerable attention owing to their antitumor activity and lamellarin D is one of the most cytotoxic compounds in the series. This compound exhibits potent anticancer activity at nanomolar concentration and is a potent inhibitor of the enzyme topoisomerase I (topoI). Although several lamellarin derivatives show potent anticancer potency in vitro, they suffer from several drawbacks that result from low water solubility and relatively labile nature of the lactone ring under basic conditions. In this work the pyrrolo[2,1-a]isoquinoline core was replaced by a beta-carbolin-1-one moiety and the labile lactone ring was substituted with a 3,4-dihydro-2H-[1,3]oxazine (2). The analogues were synthesized by an intramolecular Friedel-Crafts cyclization of appropriate indole-2-carboxilic acid beta-oxoamides, obtained by coupling 2-indole carboxylic acids and substituted 2-amino-1,2-diphenyl-ethanones. Ring-closure to give the tetracyclic core was achieved using diiodomethane under basic conditions.
Settore CHIM/06 - Chimica Organica
Design and syntheis of new Lamellarin D analogues / S. Cananzi, S. Dallavalle, L. Merlini, R. Cincinelli, L. Musso, R. Nannei. ((Intervento presentato al 12. convegno Tetrahedron Symosyum-Challenges in Organic and Biooranic Chemistry tenutosi a Sitges (Spain) nel 2011.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/158983
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