ABSTRACT
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.
Subject(s)
Alkaloids/chemical synthesis , Alkaloids/pharmacology , Alkaloids/chemistry , Animals , Biological Products/chemical synthesis , Biological Products/chemistry , Biological Products/pharmacology , Female , Humans , MCF-7 Cells , Porifera , Spectrum Analysis/methods , Structure-Activity RelationshipABSTRACT
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.
ABSTRACT
Nigricanoside A was isolated from green alga, and its dimethyl ester was found to display potent cytotoxicity. Its scarcity prevented a full structure elucidation, leaving total synthesis as the only means to determine its relative and absolute stereochemistry and to explore its biological activity. Here we assign the stereochemistry of the natural product through enantioselective total synthesis and provide initial studies of its cytotoxicity.
ABSTRACT
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.
Subject(s)
Alkaloids/chemical synthesis , Hydrocarbons, Iodinated/chemistry , Imidazoles/chemistry , Alkaloids/chemistry , Animals , Chromatography, High Pressure Liquid , Hydrogenation , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Porifera/chemistry , StereoisomerismABSTRACT
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.
Subject(s)
Alkaloids/chemistry , Alkaloids/chemical synthesis , Biological Products/chemistry , Biological Products/chemical synthesis , Imidazoles/chemistry , Imidazoles/chemical synthesis , Porifera/chemistry , Animals , Marine Biology , Molecular Structure , Nuclear Magnetic Resonance, BiomolecularABSTRACT
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.
Subject(s)
Imidazoles/chemical synthesisABSTRACT
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.
ABSTRACT
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.
Subject(s)
Imidazoles/chemical synthesis , Organic Chemicals/chemical synthesis , Alkaloids/chemistry , Imidazoles/chemistry , Molecular Structure , Organic Chemicals/chemistryABSTRACT
An investigation of the utility of N-sulfonyloxaziridines to effect the oxidative rearrangement of tetrahydrobenzimidazoles to spiro fused 5-imidazolones is reported. In addition to the anticipated rearrangement manifold, it was found that 2-amino substituted derivatives afford products resulting from rearrangement, or alternatively from addition of methanol or water depending on the nature of the N-substituents and reaction conditions.
