RESUMEN
The total synthesis of a number of representative natural products isolated from Leucetta and Clathrina sponges containing a polysubstituted 2-aminoimidazole are described. These syntheses take advantage of the site specific metallation reactions of 4,5-diiodoimidazoles resulting in the syntheses of three different classes of Leucetta derived natural products. The cytotoxicities of these natural products, along with several precursors in MCF7 cells were determined through an MTT growth assay. For comparative purposes a series of naphthimidazole-containing family members are included.
Asunto(s)
Alcaloides/síntesis química , Alcaloides/farmacología , Alcaloides/química , Animales , Productos Biológicos/síntesis química , Productos Biológicos/química , Productos Biológicos/farmacología , Femenino , Humanos , Células MCF-7 , Poríferos , Análisis Espectral/métodos , Relación Estructura-ActividadRESUMEN
An exploration of an abiotic approach to spirocalcaridines A and B is described centered on electrophile-induced dearomatizing spirocyclization of aryl enyne derivatives. Elaboration of the α-iodoenone via an Ullmann-like, copper-catalyzed amidation provided a formamide which upon treatment with methylamine undergoes a dienol-arene rearrangement, providing the corresponding kealiinine-like framework. This observation suggests a possible biosynthetic links between the spirocalcaridines and the naphthimidazole group of Leucetta alkaloids.
RESUMEN
Short total syntheses of the Leucetta-derived alkaloids, kealiinines A-C, have been accomplished using an intramolecular Friedel-Crafts-dehydration sequence of a bis benzylic diol. The precursor diol was obtained through a series of position-specific Grignard reactions from 1-methyl-4,5-diiodoimidazole. C2-Azidation and hydrogenation of the azide then provided the reported structures of kealiinines A-C. While the (1)H NMR data did not completely match for these materials, the HPLC data were consistent with the assigned structure of these alkaloids.
Asunto(s)
Alcaloides/síntesis química , Hidrocarburos Yodados/química , Imidazoles/química , Alcaloides/química , Animales , Cromatografía Líquida de Alta Presión , Hidrogenación , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Poríferos/química , EstereoisomerismoRESUMEN
Marine sponges belonging to the Calcarea family have been studied for some time and have yielded a wide variety of structurally unique secondary metabolites. In particular, these sponges have produced a large number of bioactive alkaloids containing an imidazole heterocycle, typically substituted with two benzylic fragments at various locations around the azole nucleus and at various oxidation states. This review will describe the isolation, structural determination and synthetic studies towards this growing class of natural products.
Asunto(s)
Alcaloides/química , Alcaloides/síntesis química , Productos Biológicos/química , Productos Biológicos/síntesis química , Imidazoles/química , Imidazoles/síntesis química , Poríferos/química , Animales , Biología Marina , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
Total syntheses of the cytotoxic Leucetta-derived 2-aminoimidazoles, naamine G and naamidine H, have been accomplished using a position selective metalation-benzylation sequence with a 4,5-diiodoimidazole derivative.
Asunto(s)
Imidazoles/síntesis químicaRESUMEN
Simple total syntheses of two Leucetta-derived marine alkaloids have been developed using position specific halogen-metal exchange of polyhaloimidazoles to introduce the benzyl substituted sidechains. Introduction of the C2 amine group by lithiation and trapping with tosyl azide provides amines on catalytic hydrogenation, which can be converted to naamidine G and 14-methoxynaamidine G using a procedure described in the literature.
RESUMEN
The first total synthesis of the Leucetta alkaloid calcaridine A is described based on a biosynthetic postulate. Application of an oxidative rearrangement of a 4,5-disubstituted imidazole leads to the formation of both calcaridine A and epi-calcaridine A. An X-ray crystal structure determination on the latter has allowed the assignment of the relative configuration of the epimeric natural product and calcaridine A by extrapolation.