Phytotoxins. II. Characterization of a phytotoxic fraction from alternaria alternata f. sp. lycopersici

A host-specific phytotoxic fraction obtained from the cell-free culture filtrate of A. alternata f. sp. lycopersici is shown to consist of two esters of 1,2,3-propanetricarboxylic acid and 1-amino-11,15-dimethylheptadeca-2,4,5,13,14-pentol 1. The sites of esterification are a terminal carboxyl of the acid and C₁₃ (major component 2a) and C₁₄ (2b) of 1.     

Isolation,structure elucidation,and antibacterial evaluation of the metabolites produced by the marine-sourced Streptomyces sp. ZZ820

New indole alkaloids streptoprenylindoles A–C (1–3) and diterpenoids 18-acetyl-cyclooctatin (8), 5,18-dedihydroxy-cyclooctatin (9), and 5-dehydroxy-cyclooctatin (10) were isolated from the culture of marine-derived Streptomyces sp. ZZ820, along with known 3-cyanomethyl-6-[3-methyl-2-butenyl]indole (4), N-(2-(1H-indol-3-yl)ethylacetamide (5), 1-acetyl-β-carboline (6), indole-3-methylethanoate (7), cyclooctatin (11), and chromomycin A₃ (12). Their structures were elucidated by a combination of extensive spectroscopic analyses, ECD calculation, and the Mosher's method. Streptoprenylindoles A (1) and B (2) are enantiomers that were separated through the preparation of their Mosher esters. Three new diterpenoids (8–10) showed antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli with MIC values of 24.11–55.12?μM, while chromomycin A₃ (12) showed potent antibacterial activities against MRSA (MIC: 0.59?μM) and E. coli (MIC 0.04?μM).     

Structure of the host-specific pathotoxins produced by Helminthosporium maydis, race T

Polyketo-polyalcohol structures of the host-specific pathotoxins (Band 1- and Band 2-toxins) from $\text{Helminthosporium maydis}$, race T were elucidated by NMR analysis and chemical degradations.     

Acremines H-N, novel prenylated polyketide metabolites produced by a strain of Acremonium byssoides

Five novel metabolites, acremines H-N, have been isolated from malt extract-peptone-glucose agar cultures of a strain of Acremonium byssoides. Their structures and stereochemistry were elucidated using a combination of ¹³C and ¹H homo and heteronuclear 2D NMR experiments. Acremines H-N inhibited the germination of sporangia of Plasmopara viticola.     

Structural elucidation and bioactivity of novel secondary metabolites from Carex distachya

Four new carexanes and a new seco-derivative metabolite have been isolated and characterized from the herbaceous plant Carex distachya Desf. All of the structures have been elucidated on the basis of spectroscopic data. These compounds derive from the cyclization of prenylate stylbenoid precursors. The seco-carexane is formed by a further oxidative cleavage of the C-7-C-8 bond. The absolute configurations have been determined by Mosher's method using appropriate chemical correlations. All of the carexanes A-H have been tested for their phytotoxicity against Lactuca sativa. The bioassays showed an inhibitory effect on seed germination for all compounds described in this report.     

Bioactive marine metabolites VI. Structure elucidation of discodermin a,an antimicrobial peptide from the marine sponge Discodermia kiiensis

The structure of an antimicrobial peptide discodermin A isolated from the marine sponge Discodermia kiiensis has been elucidated as CHO-d-Ala-l-Phe-d-Pro-d-t-Leu-l-t-Leu-d-Trp-l-Arg-d-Cys(O₃H)-l-T$\text{hr-}\text{l}\text{-MeGln-}\text{d}\text{-Leu-}\text{l}\text{-Asn-}\text{l}\text{-Thr-Sar}$.     

Structure elucidation of a novel funicone-like compound produced by Penicillium pinophilum

A novel metabolite related to the previously identified compound 3-O-methylfunicone (1) was isolated from the fungus Penicillium pinophilum and its structure elucidated by spectral analysis as 3-O-methyl-5, 6-epoxyfunicone (2).     

Isolation, structural elucidation, and biosynthesis of 15-norlankamycin derivatives produced by a type-II thioesterase disruptant of Streptomyces rochei

Lankamycin, a 14-membered macrolide antibiotic, contains a 3-hydroxy-2-butyl side chain at C-13. To analyze the function of lkmE, which encodes type-II thioesterase in the lankamycin cluster, we carried out a gene disruption experiment. Disruption of lkmE resulted in a 70% decrease of lankamycin production concomitant with an accumulation of novel lankamycin derivatives (LM-NS01A and LM-NS01B), in which the C-13 side chain is replaced by a 1-carboxyethyl group. The biosynthetic origin of 1-carboxyethyl group was confirmed by incorporation of deuterium in [3-²H]3-methyl-2-oxobutyrate into the C-14 position. These results indicate that the biosynthesis of LM-NS01A and LM-NS01B starts from isobutyryl CoA in place of (S)-2-methylbutyryl CoA and LkmE removes the aberrantly loaded starter unit and restores lankamycin production.     

Structure of citreoviridin,a mycotoxin produced by penicillium citreo-viride molded on rice

Structure of citreoviridin, a “yellowed rice toxin” produced by P. citreo-viride molded on rice, was determined as 1b.     

Structure elucidation of phase II metabolites by tandem mass spectrometry: an overview

The present paper provides a summary of the collision-induced dissociation of protonated and deprotonated phase II metabolites of drugs and pesticides. This overview is based on published literature and unpublished data from the authors. In particular, glutathione conjugates and their biotransformation products are discussed in detail. In addition, the fragmentation of the major classes of conjugates, i.e. glucuronides, glucosides, malonylglucosides, sulfates, acetates, methyl and glycine conjugates, is reported. Collision-induced dissociation, as studied by tandem mass spectrometry, allows the rapid identification of the type of conjugate, whereas the exact conjugation site can in general be determined only by additional NMR experiments.     

Structure elucidation of drug metabolites using thermospray liquid chromatography-mass spectrometry

Thermospray liquid chromatography-mass spectrometry (LC-MS) has been used to provide structural information both from in vitro and in vivo experiments. This paper will describe the more salient aspects of the technique that have emerged. The ability of the interface to handle gradients was essential for its successful application to metabolism studies, owing to the wide range of compound polarity involved. The examples discussed in this paper include the use of LC-MS in the analysis of in vitro incubations of drugs with hepatocyte cell cultures and the direct analysis of plasma samples from in vivo studies in the dog.     

Phytotoxins. I. A 1-aminodimethylheptadecapentol from alternaria alternata f. sp. lycopersici

The products of alkaline hydrolysis of the host-specific phytotoxic fraction T_A from A. alternata f. sp. lycopersici¹ are identified as 1,2,3,-propanetricarboxylate and either 1-amino-11,15-dimethylheptadeca-2,4,5,13,14-pentol 1 or its 7,15-dimethy1 isomer.     

Absolute stereostructures of cytotoxic metabolites, chaetomugilins A-C, produced by a Chaetomium species separated from a marine fish

Chaetomugilins A-C were isolated from a strain of Chaetomium globosum originally isolated from the marine fish Mugil cephalus, and their absolute stereostructures have been elucidated on the basis of spectroscopic analyses using 1D and 2D NMR techniques, some chemical transformations, and an X-ray analysis. This compound exhibited significant cytotoxicity against cultured P388 cells and HL-60 cells.     

Acremines A-F, novel secondary metabolites produced by a strain of an endophytic Acremonium, isolated from sporangiophores of Plasmopara viticola in grapevine leaves

Six novel metabolites, acremines A-F have been isolated from agar cultures of a strain of Acremonium sp. Their structures and stereochemistry were elucidated using a combination of ¹³C and ¹H homo and heteronuclear 2D NMR experiments and X-ray analysis. Acremines A-D inhibited the germination of sporangia of Plasmopara viticola.     

Total synthesis of alboatrin, a phytotoxic metabolite from Verticillium alboatrum

A synthesis of the phytotoxic metabolite alboatrin 1 is described. An intramolecular ketene-olefin cycloaddition followed by an oxidative ring enlargement was employed to generate the tricyclic ring system.     

Structure elucidation of some highly unusual tricyclic cis-caryophyllane sesquiterpenes from Marasmiellus troyanus

Three new unusual sesquiterpenes (1-3) were isolated from the tropical rainforest basidiomycete, Marasmiellus troyanus and their structure elucidation was achieved by NMR spectroscopy, single-crystal X-ray structural analysis and a modified Mosher’s ester method to determine the absolute stereochemistry of compound 1. These unusual metabolites are probably derived from the caryophyllane class of sesquiterpenes and a possible biosynthetic route to these compounds is proposed. These small natural products represent the best possible features of chemical diversity, being chiral and exhibiting extensive functional group chemistry highlighting the value of natural products as a screening resource for therapeutics discovery programmes.     

Structure and absolute configuration of new acidic metabolites from Stachys ehrenbergii

Two novel metabolites have been isolated from the aerial parts of Stachys ehrenberiigii. Their structures and stereochemistry were elucidated using a combination of ¹³C and ¹H homo and heteronuclear 2D NMR experiments and mass analysis. The development of an enantioselective synthesis of 3-(2′-acetoxy-4-phenylbut-3′-enoylamino)propionic acid allowed to confirm the structure and assign the (R) absolute configuration at C-2′ of the natural product.     

Structure and cytotoxicity of new metabolites from the sponge Mycale cecilia

The chemical study of the sponge Mycale cecilia has led to the isolation of 14 new pyrrole-containing metabolites. Mycalazals 3-13 are pyrrole-2-carbaldehydes possessing at C-5 hydrocarbon side chains of different length and/or number of unsaturations. Mycalenitriles 1-3 are 5-cyanoalkylpyrrole-2-carbaldehydes. The structures of the new compounds were established mainly by NMR and MS spectroscopic analysis. The location of the double bond in mycalazal-4, -8, and -11 was determined by MS analysis of the corresponding bis(methylthio) derivatives. Mycalazals have shown activity as growth inhibitors of several tumor cell lines, in particular the LNcaP cell line, being mycalazal-8 the most active metabolite.