Structure, Absolute Configuration, and Conformational Study of 12-Membered Macrolides from the Fungus Dendrodochium sp. Associated with the Sea Cucumber Holothuria nobilis Selenka

Abstract

Dendrodolides A-M (1-13), 13 new 12-membered macrolides, were isolated from Dendrodochium sp., a fungus associated with the sea cucumber Holothuria nobilis Selenka, which was collected from the South China Sea. The structures of the dendrodolides were elucidated by means of detailed spectroscopic analysis and X-ray single-crystal diffraction. The absolute configurations were assigned using the modified Mosher method, exciton-coupled circular dichroism (ECCD), electronic solution and solid-state circular dichroism (ECD) supported by time-dependent density functional theory (TDDFT) ECD calculations, and X-ray analysis. A detailed conformational analysis of the 13 derivatives indicated that the conformation of the flexible macrolide ring plays a decisive role in their chiroptical properties. Thus, it is highly recommended to apply advanced levels of theory and to avoid simple comparison of ECD spectra to determine the absolute configurations of these derivatives. In an in vitro bioassay, compounds 1-5, 7-9, 11, and 12 exhibited different levels of growth inhibitory activity against SMMC-7721 and HCT116 cells. This is the first report of 12-membered macrolides from the fungus of the genus Dendrodochium . The coisolation of four pairs of epimers is extremely interesting and indicates the complexity of β-ketoreductase stereospecificity in the biosynthesis of enigmatic iterative fungal polyketides.

Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291

“…These conformers were reoptimized at two different DFT levels, namely B3LYP/6-31G(d) in vacuo and B97D/TZVP [16–17] with a Polarizable Continuum Model (PCM) for MeCN [18]. The B3LYP optimization yielded 10 low-energy conformers above 2% Boltzmann population, while the number of low-energy conformers was 14 at the applied B97D level (Fig.…”

Hydroquinone derivatives from the marine-derived fungus Gliomastix sp.

“…38 Geometry reoptimizations were carried out at the B3LYP/6-31G(d) level in vacuo, the B3LYP/6-31+G(d,p) level in vacuo, the B97D/TZVP 20,21 and the CAMB3LYP/ TZVP 22,23 levels with the PCM solvent model for MeCN or MeOH. TDDFT ECD calculations and OR calculations were run with various functionals (B3LYP, BH&HLYP, CAM-B3LYP, PBE0) and the TZVP basis set as implemented in the Gaussian 09 package with the same or no solvent model as in the preceding DFT optimization step.…”

Absolute Configuration and Conformational Study of Psammaplysins A and B from the Balinese Marine SpongeAplysinella strongylata

“…10 In a program designed to identify antimalarial drug leads, it was found that psammaplysins F−H exhibited strong antimalarial activity. 8,9 We recently reported the isolation of psammaplysins K−W, together with 19-hydroxyplammaplysins E, P, Q, S, T, U, and W, from an extract of the Balinese sponge Aplysinella strongylata (order Verongida, family Aplysinellidae), with five of these new psammaplysins showing variation in the structural motif attached to C-16 of the aromatic ring, while the remaining compounds contained fatty acid side chains; 19-hydroxypsammaplysin E showed potent antimalarial activity. 11 The relative configuration of psammaplysin A (1) was first determined as (6S*,7S*) in 1985 by single-crystal X-ray crystallographic analysis of its diacetyl derivative (2).…”