Antimalarials and Phytotoxins from Botryosphaeria dothidea Identified from a Seed of Diseased Torreya taxifolia

The metabolic pathways in the apicoplast organelle of Plasmodium parasites are similar to those in plastids in plant cells and are suitable targets for malaria drug discovery. Some phytotoxins released by plant pathogenic fungi have been known to target metabolic pathways of the plastid; thus, they may also serve as potential antimalarial drug leads. An EtOAc extract of the broth of the endophyte Botryosphaeria dothidea isolated from a seed collected from a Torreya taxifolia plant with disease symptoms, showed in vitro antimalarial and phytotoxic activities. Bioactivity-guided fractionation of the extract afforded a mixture of two known isomeric phytotoxins, FRT-A and flavipucine (or their enantiomers, sapinopyridione and (-)-flavipucine), and two new unstable γ-lactam alkaloids dothilactaenes A and B. The isomeric mixture of phytotoxins displayed strong phytotoxicity against both a dicot and a monocot and moderate cytotoxicity against a panel of cell lines. Dothilactaene A showed no activity. Dothilactaene B was isolated from the active fraction, which showed moderate in vitro antiplasmodial activity with high selectivity index. In spite of this activity, its instability and various other biological activities shown by related compounds would preclude it from being a viable antimalarial lead.     

Microbial metabolism. Part 5. Dihydrokawain

Preparative scale fermentation of (6S)-dihydrokawain (1) with Rhizopus arrhizus (ATCC 11145) gave 3'-hydroxydihydrokawain (2) and (8S)-hydroxydihydrokawain (3). Structure elucidation of the metabolites was based on spectroscopic data. The C-8 absolute configuration of (3) was assessed via its Mosher's esters.     

Identification and biological activity of microbial metabolites of xanthohumol

Microbial transformation of xanthohumol using the culture broth of Cunninghamella echinulata NRRL 3655 afforded (2S)-8-[4"-hydroxy-3"-methyl-(2"-Z)-butenyl]-4',7-dihydroxy-5-methoxyflavanone (5) and (2S)-8-[5"-hydroxy-3"-methyl-(2"-E)-butenyl]-4',7-dihydroxy-5-methoxyflavanone (6). Xanthohumol (1) and flavanone 6 as well as (E)-2"-(2"'-hydroxyisopropyl)-dihydrofurano[2",3":4',3']-2',4-dihydroxy-6'-methoxychalcone (2), (2S)-2"-(2"'-hydroxyisopropyl)-dihydrofurano[2",3":7,8]-4'-hydroxy-5-methoxyflavanone (3) obtained with Pichia membranifaciens showed antimalarial activity against Plasmodium falciparum.     

Microbial metabolism. Part 6. Metabolites of 3- and 7-hydroxyflavones

Fermentation of 3-hydroxyflavone (1) with Beauveria bassiana (ATCC 13144) yielded 3,4'-dihdroxyflavone (3), flavone 3-O-beta-D-4-O-methylglucopyranoside (4) and two minor metabolites. 7-Hydroxyflavone (2) was transformed by Nocardia species (NRRL 5646) to 7-methoxyflavone (5) whilst Aspergillus alliaceus (ATCC 10060) converted it to 4',7-dihydroxyflavone (6). Flavone 7-O-beta-D-4-O-metylglucopyranoside (7) and 4'-hydroxyflavone 7-O-beta-D-4-O-methylglucopyranoside (8) were the metabolic products of 7-hydroxyflavone (2) when fermented with Beauveria bassiana (ATCC 7159). One of the minor metabolites of 3-hydroxyflavone (1) was tentatively assigned a beta'-chalcanol structure (9). Compounds 4, 7 and 8 are reported as new compounds. Structure elucidation of the metabolites was based on spectroscopic data.     

Podocarpaside, a triterpenoid possessing a new backbone from Actaea podocarpa

Podocarpaside (1), a novel arabinoside possessing a unique triterpene skeleton was isolated from Actaea podocarpa, a closely related species to black cohosh (dietary supplement used for menopausal disorders). Podocarpaside belongs to a new class of triterpenoids, for which the name "ranunculane" is proposed. Compound 1 possesses anticomplement activity. [structure: see text].     

Antifungal cyclopentenediones from Piper coruscans

Coruscanones A and B, two new antifungal cyclopentenedione derivatives, have been isolated from Piper coruscans and their structures elucidated by spectroscopic and chemical methods. Coruscanone A exhibits significant antifungal activity against Candida albicans and its azole-resistant strains and may serve as a template for a new class of antifungal agents.     

Deconvolution of E/Z tetrahydroisoquinoline amide rotamers and conformers from a marine-derived Streptomyces strain

A collaborative program to discover new specialized metabolites from aquatic environments of Iceland led to the deconvolution of tetrahydroisoquinoline amide E/Z rotamers [(E/Z)-N-acetyl-MY336-a; 1] and conformers produced by a Streptomyces sp. All structures were elucidated by NMR and MS analysis, and interpretation of electronic circular dichroism (ECD) data. ECD and optical rotation (OR) simulations permitted the unequivocal assignment of the absolute configuration of compound 1 and provided an important example of delineating the spectroscopic contributions of equilibrating rotamers and boat/chair conformers of a common natural product scaffold.     

(+)-Africanal,a new lignan of the aryltetrahydronaphthalene class

The absolute configuration (1R,2R,3R,3aS) and structural relationships of africanal, a novel lignan from Olea africana, are defined.     

Enantiomeric discorhabdin alkaloids and establishment of their absolute configurations using theoretical calculations of electronic circular dichroism spectra

Enantiomeric pairs of the cytotoxic pyrroloiminoquinone marine alkaloids discorhabdins B (2), G*/I (3), L (4), and W (5) have been isolated from Latrunculia species sponges collected at different locations around the coast of New Zealand. The absolute configuration of all compounds was secured by comparison of observed data with the results of time-dependent density functional theory (TDDFT) calculations of electronic circular dichroism (ECD) spectra. Enantiomeric discorhabdins exhibit equipotent antiproliferative biological activity.     

Methylalumoxane MCM-41 as Support in the Co-Oligomerization of Ethene and Propene with [{C2H4(1-indenyl)2}Zr(CH3)2]

Superior to the homogeneous catalyst or physisorbed catalyst system is a system with the ansa-metallocene catalyst [{C₂H₄(1-ind)₂}Zr(CH₃)] on a support formed by covalently anchoring methylalumoxane (MAO) on the internal pore walls of MCM-41. This system is a highly active and shape-selective mesoporous host in the co-oligomerization [shown schematically in Equation (a)] of ethene and propene with ansa-metallocenes. TMA=trimethylaluminum, ind=indenyl.