Halogenated terpenoids. XXXII - Pentabromides from limonene two 1,2,8,9,9-pentabromo-p-menthanes

The problems of structure in diastereomers where one chiral centre is remote from another are further investigated in the 1,2,8,9,9-pentabromo-p-menthane series.

9,10-Dihydroxy-1,8-cineole (1,3,3-Trimethyl-2-oxabicyclo[2.2.2]octane-10,11-diol)

The title compound (3) has been synthesized and its presence sought in the urinary metabolites of the brushtail possum. © CSIRO 2001

The reaction of 8-amino-p-menthene derivatives with electrophiles

Attempts to ring-close the nitrogen atom of 8-amino-p-menth-1-ene and of N-substituted 8-amino-p-menth-1-enes onto the C1 - C2 double-bond carbons has led to a range of bicyclo[2.2.2] and bicyclo[3.2.1] products, together with the novel bicyclo[4.3.1]-1,3-oxazepine 9.

The 1,3-diaxial dibromo interaction

The non-bonding interaction between two bromine atoms sited 1,3-diaxially on a simple cyclohexane ring is explored by X-ray crystallography. The ring is distorted to allow the bromine atoms an interatomic distance of 3.54 angstrom.

Multilabeled classification approach to find a plaint source for terpenoids

Recently, we have built a classification model that is capable of assigning a given sesquiterpene lactone (STL) into exactly one tribe of the plant family Asteraceae from which the STL has been isolated. Although many plant species are able to biosynthesize a set of peculiar compounds, the occurrence of the same secondary metabolites in more than one tribe of Asteraceae is frequent. Building on our previous work, in this paper, we explore the possibility of assigning an STL to more than one tribe (class) simultaneously. When an object may belong to more than one class simultaneously, it is called multilabeled. In this work, we present a general overview of the techniques available to examine multilabeled data. The problem of evaluating the performance of a multilabeled classifier is discussed. Two particular multilabeled classification methods-cross-training with support vector machines (ct-SVM) and multilabeled k-nearest neighbors (M-L-kNN)were applied to the classification of the STLs into seven tribes from the plant family Asteraceae. The results are compared to a single-label classification and are analyzed from a chemotaxonomic point of view. The multilabeled approach allowed us to (1) model the reality as closely as possible, (2) improve our understanding of the relationship between the secondary metabolite profiles of different Asteraceae tribes, and (3) significantly decrease the number of plant sources to be considered for finding a certain STL. The presented classification models are useful for the targeted collection of plants with the objective of finding plant sources of natural compounds that are biologically active or possess other specific properties of interest.

Antimicrobial Activity of Terpenoids from Copaifera langsdorffii Desf. Against Cariogenic Bacteria

In the present work, the anticariogenic activities of nine labdane type-diterpenes and four sesquiterpenes were investigated. Among these metabolites, (-)-copalic acid (CA) was the most active compound displaying MIC values very promising (ranging from 2.0 to 6.0 mu g/mL) against the main microorganisms responsible for dental caries: Streptococcus salivarius, S. sobrinus, S. mutans, S. mitis, S. sanguinis and Lactobacillus casei. Time kill assays performed with CA against the primary causative agent (S. mutans) revealed that, in the first 12 h, this compound only inhibits the growth of the inoculum (bacteriostatic effect). However, its bactericidal effect is clearly noted thereafter (between 12 and 24 h). Also, CA did not show a synergistic effect when combined with the anticariogenic gold standard (chlorhexidine, CHD) in the checkerboard assays against S. mutans. In conclusion, the results points out CA as an important metabolite in the search for new effective anticariogenic agents. Copyright (C) 2010 John Wiley & Sons, Ltd.

Geographic variation of natural products of tropical nudibranch Asteronotus cespitosus

Extracts of the dorid nudibranch Asteronotus cespitosus from two geographically separate regions of Australia and from the Philippines were compared using thin-layer, high-performance liquid and gas chromatography and H-1 NMR analysis. Halogenated metabolites were detected in all mollusk specimens. The major component detected in digestive tissue of specimens from the Great Barrier Reef in northeastern Australia was 4,6-dibromo2-(2',4'-dibromophenoxy)phenol (1), with minor amounts of 3,5-dibromo-2(3',5'-dibromo-20-methoxyphenoxy)phenol (2). In a specimen collected from northwestern Australia, only 3,5-dibromo-2-(3',5'-dibromo-2'-methoxyphenoxy)phenol was found. The specimen from the Philippines contained 2,3,4,5-tetrabromo-6-(2'-bromophenoxy) phenol (3) together with a novel chlorinated pyrrolidone (4). In addition, the sesquiterpenes dehydroherbadysidolide (5) and spirodysin (6) were detected in the digestive organs and mantle tissue of the nudibranchs from the Great Barrier Reef and from the Philippines, whereas these chemicals were not found in the specimen from northwestern Australia. All of the chemicals (1-3,5, and 6) have previously been isolated from the sponge Dysidea herbacea, as have chlorinated metabolites related to 4. This is the first time the characteristic halogenated metabolites that typify Dysidea herbacea have been reported from a carnivorous mollusk, which implies a dietary origin as opposed to de novo synthesis.

Sponge halogenated natural products found at parts-per-million levels in marine mammals

Several unknown, abundant brominated compounds (BCs) were recently detected in the blubber of dolphins and other marine mammals from Queensland (northeast Australia). The BC were interpreted as potential natural products due to the lack of anthropogenic sources for these compounds. This study investigated whether some of the BCs accumulated by diverse marine mammal species are identical with natural BCs previously isolated from sponges (Dysidea sp.) living in the same habitat. Isolates from sponges and mollusks (Asteronotus cespitosus) were compared with the signals detected in the mammals' tissue. Mass spectra and gas chromatography retention times on four different capillary columns of the isolates from sponges and mammals were identical in all respects. This proves that the chemical name of the compound previously labeled BC-2 is 4,6-dibromo-2-(2'-dibromo)phenoxyanisole and that the chemical name of BC-11 is 3,5-dibromo-2-(3',5'-dibromo-2'-methoxy)phenoxyanisole. Using a quantitative reference solution of BC-2, we established that the concentrations of the brominated metabolies found in the marine mammals are frequently >1 mg/kg. The highest concentration (3.8 mg/kg), found in a sample of pygmy sperm whale (Kogia breviceps), indicates that BC-2 is a bioaccumulative, natural organohalogen compound. This is supported by the concentrations of the BCs in our samples being equal to the highest concentrations of anthropogenic BCs in any environmental sample. The quantitative determination of BC-2 in blubber of marine mammals from Africa and the Antarctic suggests that BC-2 is wide-spread. These results are direct proof that marine biota can produce persistent organic chemicals that accumulate to substantial concentrations in higher trophic organisms.

Remediation of sandy soils contaminated with hydrocarbons and halogenated hydrocarbons by soil vapour extraction

This paper presents the study of the remediation of sandy soils containing six of the most common contaminants (benzene, toluene, ethylbenzene, xylene, trichloroethylene and perchloroethylene) using soil vapour extraction (SVE). The influence of soil water content on the process efficiency was evaluated considering the soil type and the contaminant. For artificially contaminated soils with negligible clay contents and natural organic matter it was concluded that: (i) all the remediation processes presented efficiencies above 92%; (ii) an increase of the soil water content led to a more time-consuming remediation; (iii) longer remediation periods were observed for contaminants with lower vapour pressures and lower water solubilities due to mass transfer limitations. Based on these results an easy and relatively fast procedure was developed for the prediction of the remediation times of real soils; 83% of the remediation times were predicted with relative deviations below 14%.

Some progress on the chemistry of natural bioactive terpenoids form Chinese medicinal plants

(1) Pseudolaric acids - Novel diterpenes, Pseudolaric acid A, B, C and D were isolated from Pseudolarix kaempferi Gorden (pinaceae). Their structures were assigned by spectroscopic data and chemical correlations. In the contineous studies, the absolute configurations, the conformations in the solutions, the framentation mechanisms of MS and assigments of all NMR spectral signals were also reported. They showed the antifungal and cytotoxic activities. (2) Daphnane diterpenes - In the further studies on the plants of Thymelaeaceae, besides 10 known diterpenes, 16 new daphnane diterpenes were isolated from Daphne genkwa, D. tangutica, D. giraldii, Wikstroemie chamaedaphne. They showed the antifertilities activities. (3) Tripterygium diterpenes 14 new diterpenes were isolated from Triperygium wilfordii, T. regeli and T. hypoglaucum. Some of them showed the antitumor activities. The CD spectra showed that A/B ring of all compoundshave trans configuration as same as tripdiolide and triptolide determined by X-ray diffraction (4) Pregnane glycosides from Marsdenia koi - Two new pregnane glycosides marsdenikoiside A and marsdenikoiside B which can terminate the early pregnancy were isolated from Marsdeia koi. Their structures were elucidated by hydrolysis and spectroscopic methods.

Synthesis and antifungal activity of halogenated aromatic bis-γ-lactones analogous to avenaciolide

Here we describe the total syntheses and characterization by elemental analyses, infrared and NMR spectroscopy of three new compounds analogous to avenaciolide, a bis-γ-lactone isolated from Aspergillus avenaceus that possesses antifungal activity, where the octyl group of the natural product was replaced by aromatic groups containing chlorine and fluorine atoms. The effects of the avenaciolide, the novel compounds and their synthetic precursors on mycelia development and conidia germination of Colletotrichum gloeosporioides and Fusarium solani were evaluated in vitro. The title compounds were almost as active as avenaciolide. The absolute structures of the chlorinated analogs were determined by X-ray diffraction analysis.

An investigation into fungal metabolism of halogenated and related steroids

Fungal metabolism of halogenated and related steroids was investigated. The fungi Aspergillus niger ATCC 9142, Curvularia lunata NRRL 2380 and Rhizopus stolonifer ATCC6227b were studied in this regard. 2l-Fluoro-, 2l-chloro, 2l-bromo- and 2l-methyl-pregn-4-ene-3,20diones were prepared and incubated with ~ niger (a C-2l-hydroxylator) in order to observe the effect of the C-2l substituent on the metabolism of these substrates. In all four cases, the C-2l substituent prevented any significant metabolism of these substrates. llB-Fluoropregn-4-ene-3,20-dione was prepared and incubated with C. lunata (an llB-hydroxylator) and ~ stolonifer (an lla-hydroxylator). With ~ lunata, the ll-fluoro- substituent prevent hydroxylation at the 11 position, but diverted it to a site remote from the fluorine atom. In contrast, with ~ stolonifer the llB-fluoro- substituent, although slowing the apparent rate of hydroxylation, did not prevent its occurrence at the 11a- position. llB-Hydroxypregn-4-ene-3,20-dione was also incubated with R. stolonifer. The llB-hydroxy-;group did not appear to have any significant effect on hydroxylation at the lla- position. The incubation of a substrate, unsaturated at a favoured site of hydroxylation with Rhizopus arrhizus ATCC 11145 provided a complex mixture of products; among them were both the a and S epoxides. The formation of these products is rationalized as arising because of the lack of regio- and stereospecificity of the hydroxylase enzyme(s) involved.

Terpenoids from the seeds of Artemisia annua

Fourteen sesquiterpenes, three monoterpenes and one diterpene natural product have been isolated from the seeds of Artemisia annua. The possible biogenesis of some of these natural products are discussed by reference to recently reported experimental results for the autoxidation of dihydroartemisinic acid and other terpenoids from Artemisia annua. (C) 2003 Elsevier Ltd. All rights reserved.

Radiative forcing and global warming potentials of 11 halogenated compounds

Radiative forcing values have been calculated for 11 halogenated compounds which are in current use or which have been suggested as possible replacements for the chlorofluorocarbons. Absorption cross-sections measured over a range of atmospheric temperature and pressure conditions as part of a multi-laboratory programme have been used together with a narrow band radiative transfer model. We provide a “best estimate” radiative forcing taking into account the likely vertical profile of the gas in each case. The Global Warming Potential over a variety of time horizons has also been calculated where the lifetime is available. We present the first such information for 1,2-dichloroethane. For chloroform our radiative forcing is 5 times higher than the value used in previous assessments, possibly because these ignored the effect of absorption outside the 800–1200 cm−1 “window”. For several of the other compounds considered here, our forcing is between 10 and 30% lower than previous assessments. The perfluorocarbons have been found to have large global warming potentials, many times that of CFC-11, due to both strong absorption and long lifetimes. The importance of absorption features at wavenumbers below 800 cm−1 and the effect of temperature variations in absorption cross-section on the radiative forcing are also investigated.

Infrared absorption spectra, radiative efficiencies, and global warming potentials of newly-detected halogenated compounds: CFC-113a, CFC-112 and HCFC-133a

CFC-113a (CF3CCl3), CFC-112 (CFCl2CFCl2) and HCFC-133a (CF3CH2Cl) are three newly detected molecules in the atmosphere that are almost certainly emitted as a result of human activity. It is important to characterise the possible contribution of these gases to radiative forcing of climate change and also to provide information on the CO2-equivalence of their emissions. We report new laboratory measurements of absorption cross-sections of these three compounds at a resolution of 0.01 cm−1 for two temperatures 250 K and 295 K in the spectral range of 600–1730 cm−1. These spectra are then used to calculate the radiative efficiencies and global warming potentials (GWP). The radiative efficiencies are found to be between 0.15 and 0.3 W∙m−2∙ppbv−1. The GWP for a 100 year time horizon, relative to carbon dioxide, ranges from 340 for the relatively short-lived HCFC-133a to 3840 for the longer-lived CFC-112. At current (2012) concentrations, these gases make a trivial contribution to total radiative forcing; however, the concentrations of CFC-113a and HCFC-133a are continuing to increase. The 2012 CO2-equivalent emissions, using the GWP (100), are estimated to be about 4% of the current global CO2-equivalent emissions of HFC-134a