Absolute Configuration of Eight Cephalimysins Isolated from the Marine‐Derived Aspergillus fumigatus.

Abstract

Eight new metabolites with spiro-heterocyclic g-lactam cores, cephalimysins E-L, were isolated from a culture broth of Aspergillus fumigatus that was originally separated from the marine fish Mugil cephalus. In spite of the presence of six chiral centers in cephalimysins E-L, no other diastereomers of them were isolated from the natural source except for eight unnatural forms that could be obtained by treating cephalimysins E-L with acidic methanol. The occurrence of cephalimysins E-L was rationalized via molecular energy calculations by assuming that these isomers were derived from annelation of a spiro-heterocyclic g-lactam with an E-olefin on the side chain such as the E-isomer of pseurotin A. Biosynthetic consideration of the metabolites based on molecular orbital calculations demonstrated that the 16 stereoisomers can all exist, and their stereochemistry was unambiguously determined using circular dichroism spectra, nuclear Overhauser effect spectroscopy, and two-dimensional nuclear magnetic resonance spectra.

Marine natural products

“…Molecular orbital calculations were used to propose a plausible biosynthetic route to the cephalimysins via an intramolecular annulation. 162 Separate co-cultures of marine sediment derived A. fumigatus with each of two terrestrial bacterial strains led to dual induction of metabolites in both organisms. In axenic culture, A. fumigatus produced the diketopiperazine brevianamide X 315 but in co-culture with one strain of bacteria, production of the indole alkaloid luteoride D 316 and heterospirocycle pseurotin G 317 was induced whilst the bacterium was induced to produce a peptide.…”

The Biological and Chemical Diversity of Tetramic Acid Compounds from Marine-Derived Microorganisms

“…Fifteen cephalimysins and their analogue FD-838, containing a spiroheterocyclic γ-lactam motif and six chiral centers, were found in the marine Aspergillus fumigatus. The fermentation broth of A. fumigatus OUPS-T106B-5 provided a class of 3-STAs consisting of cephalimysins A-L (89-100) and FD-838 (103) [92][93][94][95]. Among them, compounds 90-92 are diastereomers of 103 [93], which was first reported in a patent as being able to induce differentiation of leukemic cells, as well as to have antibacterial and antifungal activities [81,96].…”

Recent Discovery of Heterocyclic Alkaloids from Marine-Derived Aspergillus Species

“…Compound 83 was produced by a coculture of gorgonian-derived fungal strains of A. sclerotiorum and P. citrinum and characterized as a pyrrole analog [49]. Compounds 84-91 were identified and characterized as having a spiro-heterocyclic γ-lactam skeleton and they were isolated from a culture broth of the marine fish-associated endophytic fungi A. fumigatus [50]. Compounds 92-96 were characterized as four aspochalasin analogs and they were obtained from the intestines of the marine isopod Ligia oceanica, collected along the coast of Dinghai in Zhoushan, Zhejiang Province, China [51][52][53].…”

“…Moreover, the producing strains of 21, 22, and 54-56 originated from marine shrimp or prawns [34,45], while those of compounds 12-15 were derived from an unidentified colonial ascidian that was collected at Shikotan Island in the Pacific Ocean [29]. In addition to these producing strains of marine invertebrate origin, only one fungal strain, which produced 84-91, was obtained from the marine fish Mugil cephalus, representing vertebrates [50]. It appears that the number of the fungal strains of marine plant origin that produce heterocyclic alkaloids is much less than that of marine invertebrate and vertebrate origin.…”