Dehydroherbarin

Herbarin A and B were isolated from the fungal strains of Cladosporium herbarum found in marine sponges Aplysina aerophoba and Callyspongia aerizusa. Total synthesis of Herbarin A and B was achieved by carrying out a multi-step synthesis approach, and the antioxidant properties were evaluated using FRAP assay. Toxicity of these compounds was determined using a zebrafish embryo model.

In an attempt to explore the biosynthetic potential of endosymbiotic fungi, the secondary metabolite profiles of the endophytic fungus,Anteagloniumsp. FL0768, cultured under a variety of conditions were investigated. In potato dextrose broth (PDB) medium,Anteagloniumsp. FL0768 produced the heptaketides, herbaridine A (1), herbarin (2), 1-hydroxydehydroherbarin (3), scorpinone (4), and the methylated hexaketide 9S,11R-(+)-ascosalitoxin (5). Incorporation of commonly used epigenetic modifiers, 5-azacytidine and suberoylanilide hydroxamic acid, into the PDB culture medium of this fungus had no effect on its secondary metabolite profile. However, the histone acetyl transferase inhibitor, anacardic acid, slightly affected the metabolite profile affording scorpinone (4) as the major metabolite together with 1-hydroxydehydroherbarin (3) and a different methylated hexaketide, ascochitine (6). Intriguingly, incorporaion of Cu2+into the PDB medium enhanced production of metabolites and drastically affected the biosynthetic pathway resulting in the production of pentaketide dimers, palmarumycin CE4(7), palmarumycin CP4(8), and palmarumycin CP1(9), in addition to ascochitine (6). The structure of the new metabolite7was established with the help of spectroscopic data and by MnO2oxidation to the known pentaketide dimer, palmarumycin CP3(10). Biosynthetic pathways to some metabolites inAnteagloniumsp. FL0768 are presented and possible effects of AA and Cu2+on these pathways are discussed.

Hexa-2,5-dienoates, susceptible to isomerization by acids and bases, are suitable for the [4+2] anionic annulation to give 3-(2-alkenyl)naphthoates in regiospecific manner. When combined with intramolecular carbonyl-ene reaction (ICE), the accessibility of the naphthoates culminates in a new synthesis of anthraquinones and diastereoselective synthesis of tetrahydroanthraquinones. This strategy has also resulted in a 3-step synthesis of dehydroherbarin from a 3-methallylnaphthoate.

The reactive intermediates generated by the addition of alkyl, aryl, and alicyclic isocyanides to dialkyl acetylenedicarboxylates were trapped by 2,5-dihydroxycyclohexa-2,5-diene-1,4-dione or 2-hydroxynaphthalene-1,4-dione to produce highly functionalized bis(4H-chromene)- and 4H-benzo[g]chromene-3,4-dicarboxylate derivatives in fairly good yields in CH(3)CN at room temperature. These compounds are closely related to the ring systems pentalongin, dehydroherbarin, 1,3-disubstituted-3,4-dehydropyranonaphthoquinones, and 3-arylpyranonaphthoquinones, which have a broad spectrum of biological activity.