Search

Hit anti-leishmanial saponin structures selected following primary and secondary screening., Leishmaniasis is a neglected tropical disease caused by insect-vector borne protozoan parasites of the, Leishmania species. Whilst infection threatens and affects millions of the global poor, vaccines are absent and drug therapy limited. Extensive efforts have recently been made to discover new leads from small molecule synthetic compound libraries held by industry; however, the number of new chemical entities identified and entering development as anti-leishmanials has been very low. This has led to increased interest in the possibility of discovering naturally derived compounds with potent antileishmanial activity which may be developed towards clinical applications. Plant-derived triterpenoid and steroidal saponins have long been considered as anti-microbials and here we describe an investigation of a library of 137 natural (9) and semi-synthetic saponins (128) for activity against Leishmania mexicana, a causative agent of cutaneous leishmaniasis. The triterpenoid sapogenin, hederagenin, readily obtained in large quantities from Hedera helix (common ivy), was converted into a range of 128 derivatives. These semi-synthetic compounds, as well as saponins isolated from ivy, were examined with a phenotypic screening approach to identify potent and selective anti-leishmanial hits. This led to the identification of 12 compounds, including the natural saponin gypsogenin, demonstrating high potency (ED50 < 10.5 μM) against axenic L. mexicana amastigotes, the mammalian pathogenic form. One of these, hederagenin disuccinate, was sufficiently non-toxic to the macrophage host cell to facilitate further analyses, selectivity index (SI) > 10. Whilst this was not active in an infected cell model, the anti-leishmanial properties of hederagenin-derivatives have been demonstrated, and the possibility of improving the selectivity of natural hederagenin through chemical modification has been established.

Cells of Mycobacterium alvei are known to contain a unique set of mycolic acids with a (ω-1)-methoxy group; although the various enzymes in the biosynthesis of other types of mycolic acid have been widely studied, the biosynthetic route to this substituent is unclear. We now define the stereochemistry of the (ω-1)-methoxy fragment as R, and describe the synthesis of a major R-(ω-1)-methoxy-mycolic acid and its sugar esters, and of two natural M. alvei diene mycolic acids.

R- and S-Glycerol mycolates derived from single synthetic α-, keto- and methoxy-mycolic acids are described.

We report the synthesis of three stereoisomers of a mycolic acid from Mycobacterium tuberculosis containing a di-cis-cyclopropane and of two stereoisomers of a mycolic acid containing a proximal trans-cyclopropane and a distal cis-cyclopropane.

Fragments of mycobacterial cell walls such as arabinoglycerol mycolate and dimycoloyl diarabinoglycerol, comprising complex mixtures of mycolic acids, have immunostimulatory and antigenic properties. A related di-mycoloyl tri-arabinofuranosyl glycerol fragment has been isolated from cell wall hydrolysates. An effective stereoselective synthesis of tri-arabinofuranosyl glycerol, followed by coupling with stereochemically defined mycolic acids of different structural classes, to provide unique di-mycoloyl tri-arabinofuranosyl glycerols is now described.

The cell wall of mycobacteria is characterised by glycolipids composed of different classes of mycolic acids (MAs; alpha-, keto-, and methoxy-) and sugars (trehalose, glucose, and arabinose). Studies using mutant Mtb strains have shown that the structure of MAs influences the inflammatory potential of these glycolipids. As mutant Mtb strains possess a complex mixture of glycolipids, we analysed the inflammatory potential of single classes of mycolate esters of the Mtb cell wall using 38 different synthetic analogues. Our results show that synthetic trehalose dimycolate (TDM) and trehalose, glucose, and arabinose monomycolates (TMM, GMM, and AraMM) activate bone marrow-derived dendritic cells in terms of the production of pro-inflammatory cytokines (IL-6 and TNF-α) and reactive oxygen species, upregulation of costimulatory molecules, and activation of NLRP3 inflammasome by a mechanism dependent on Mincle. These findings demonstrate that Mincle receptor can also recognise pentose esters and seem to contradict the hypothesis that production of GMM is an escape mechanism used by pathogenic mycobacteria to avoid recognition by the innate immune system. Finally, our experiments indicate that TMM and GMM, as well as TDM, can promote Th1 and Th17 responses in mice in an OVA immunisation model, and that further analysis of their potential as novel adjuvants for subunit vaccines is warranted.

Routes to single enantiomers of hydroxy, methoxy and ketomycolic acids containing an α-methyl-trans-alkene unit as well as related trehalose, glucose, arabinose and glycerol esters are described. In serodiagnostic assays to detect antibodies to mycobacterial lipids, the trehalose esters give higher responses to the serum of patients with culture positive tuberculosis than to that of culture negative patients.

The synthesis of mycobacterial mycolic acid related wax esters and of their trehalose di- and mono-esters is described. The trehalose dimycolates (TDMs) synthesised activated bone marrow derived dendritic cells (BMDCs) in vitro more strongly than trehalose dibehenate or the trehalose monomycolates (TMMs). The inflammatory effects were similar to those of TDM from either a synthetic keto- or methoxy-mycolic acid, but somewhat stronger than those of a TDM from an α-mycolic acid. In vivo, the effects of one wax ester TDM were similar to those of the methoxy-MA and α-mycolic acid TDMs and trehalose dibehenate.

Mycolic acid methyl esters were extracted from Mycobacterium avium by a mild saponification protocol, designed to preserve labile components. The resulting mixture of α-, keto- and wax ester mycolates was accompanied by some degraded ω-carboxymycolic acid dimethyl esters, whose overall structures were found to support previous studies. Chromatography of the mono-carboxylic mycolates gave an inseparable mixture of keto- and wax ester mycolates and separate α-mycolates. Reduction of the ketomycolate components allowed isolation and characterisation of intact wax ester mycolates for the first time. Minor α- and ω-carboxymycolates were detected in which methyl branches were located on either the proximal or distal sides of trans-alkene groups.

The synthesis of an α'-mycolic acid of Mycobacterium smegmatis and other mycobacteria, containing a cis,cis-diene, and of the trehalose mono- and di-mycolates of this, and of a related α'-mycolic acid containing one cis-alkene, is reported.

Synthetic mycolic acids matching the overall structure of the major mycolic acids of Mycobacterium tuberculosis are coupled to trehalose to generate the corresponding synthetic trehalose monomycolate (TMM) and trehalose dimycolate (TDM; cord factor), either with two identical or two different mycolic acids.

We report the synthesis of single enantiomers of epoxy-mycolic acids containing an α-methyl- trans -alkene or a cis -cyclopropane with structures that match those of major isomers of such molecules present in complex mixtures in Mycobacteria such as Mycobacterium fortuitum or Mycobacterium smegmatis

Reaction of the bis-dibromocarbene adduct of cyclonona-1,4,7-triene with methyllithium leads to a mixture of meso and racemic cycloundeca-1,2,5,6,9-pentaenes; the former rearranges at ambient temperature through a set of pericyclic reactions.

Functional derivatives of gem-dibromocyclopropanes (ethers and esters of gemdibromocyclopropylmethanol, 2,2-dibromocyclopropanecarboxylic acids and their esters) undergo partial hydrodebromination at the treatment with isopropyl magnesium bromide (3–6 mol-equiv) in THF and then in methanol at −60°C affording the corresponding monobromides in 64–95% yields. The addition of nonsolvated magnesium bromide to the reaction mixture results in the considerable reduction of the amount of the Grignard reagent (from 6 to 3 mol-equiv). This allows achieving the partial hydrodebromination of 2,2-dibromocyclopropanecarboxylic acids.

Cell wall mycolic acids (MA) from Mycobacterium tuberculosis (M.tb) are CD1b presented antigens that can be used to detect antibodies as surrogate markers of active TB, even in HIV coinfected patients. The use of the complex mixtures of natural MA is complicated by an apparent antibody cross-reactivity with cholesterol. Here firstly we report three recombinant monoclonal scFv antibody fragments in the chicken germ-line antibody repertoire, which demonstrate the possibilities for cross-reactivity: the first recognized both cholesterol and mycolic acids, the second mycolic acids but not cholesterol, and the third cholesterol but not mycolic acids. Secondly, MA structure is experimentally interrogated to try to understand the cross-reactivity. Unique synthetic mycolic acids representative of the three main functional classes show varying antigenicity against human TB patient sera, depending on the functional groups present and on their stereochemistry. Oxygenated (methoxy- and keto-) mycolic acid was found to be more antigenic than alpha-mycolic acids. Synthetic methoxy-mycolic acids were the most antigenic, one containing a trans-cyclopropane apparently being somewhat more antigenic than the natural mixture. Trans-cyclopropane-containing keto- and hydroxy-mycolic acids were also found to be the most antigenic among each of these classes. However, none of the individual synthetic mycolic acids significantly and reproducibly distinguished the pooled serum of TB positive patients from that of TB negative patients better than the natural mixture of MA. This argues against the potential to improve the specificity of serodiagnosis of TB with a defined single synthetic mycolic acid antigen from this set, although sensitivity may be facilitated by using a synthetic methoxy-mycolic acid.

1-Trimethylsilyl-3-phenylcyclopropene undergoes a highly stereocontrolled ene-reaction to give a dimer and further reaction leads to one or more trimers derived through two ene-reactions.

A convenient and inexpensive approach to the generation of 3-phenylcyclopropenes is described. Reaction of these compounds with a range of dienophiles and dipolarophiles led to the stereoselective formation of [4+2]- and [3+2]-cycloadducts, which were exclusively exo -3-phenyl- cis -1,2-disubstituted cyclopropanes. Efficient trapping of 1-lithio-3-phenylcyclopropene with different electrophiles is also discussed. Ab initio calculations suggest that the lowest energy conformation of 3-phenylcyclopropene has the plane of the benzene ring perpendicular to the cyclopropene π-bond but with a low rotation barrier.

Synthetic mycolic acids matching the overall structure of the major α- and methoxy-mycolic acids of Mycobacterium tuberculosis are coupled to trehalose to generate the corresponding synthetic trehalose dimycolate (TDM; cord factor) and trehalose monomycolate (TMM).

Potential cellulose-surface active aryl ammonium compounds that may also de-aggregate dye molecules in aqueous solution have been modelled using molecular mechanics methods and simulation methods, and compared with known additives such as amines and urea, as an extrapolation of modelling the interaction of water and urea molecules with cellulose microfibril surfaces. The results from these modelling studies have clearly elucidated the way in which polar molecules interact with cellulose surfaces, and have been used to provide insight into the dyeing process and to identify which new molecular systems might be predicted to act as molecular delivery agents for assisting dye processes.

One chlorophyll rich fraction and two lignin preparations were separated from perennial grass and cocksfoot grass by sequential three‐stage treatments with 80% ethanol containing 0.2% NaOH, 2.5% H2O2−0.2% EDTA containing 1.5% NaOH, and 2.5% H2O2−0.2% TAED containing 1.0% NaOH at 75°C for 3 h, respectively, which released 4.6 and 3.6% chlorophyll rich fraction, 2.3 and 5.8%, and 0.9 and 1.0% lignin preparations, except for releasing 8.0 and 10.4%, 79.1 and 77.0%, and 12.9 and 12.5% of the original hemicelluloses, respectively. The lignin fractions obtained from the two different grasses had very similar molecular weights and structural composition. The NMR spectra of the lignin preparations revealed the presence of p‐hydroxyphenyl, guaiacyl, and syringyl structures, and the lignin in chlorophyll rich fraction contained more guaiacyl and syringyl units than p‐hydroxyphenyl unit, whereas the reverse trend was found in the two lignin preparations. The lignin preparations are distinguished with straw ...

In this study, de-juiced Italian ryegrass and timothy grass were successfully fractionated into one chlorophyll rich fraction, two lignin fractions, two hemicellulosic preparations, and one cellulosic fraction by sequential processes with 80% ethanol containing 0.2% NaOH, 2.5% H 2 O 2 –0.2% EDTA containing 1.5% NaOH, and 2.5% H 2 O 2 –0.2% TAED containing 1.0% NaOH at 75 °C for 3 h, respectively. The yields of chlorophyll rich fraction and total lignin fraction were found to be 6.1 and 11.0% from de-juiced Italian ryegrass, and 12.7 and 13.2% from de-juiced timothy grass. It should be noted that the two chlorophyll rich fractions contained noticeable amounts of contaminated hemicelluloses (17.1–18.8%) and lignin, whereas the four lignin fractions contained only small amounts of bound hemicelluloses (5.6–8.6%). Nitrobenzene oxidation and NMR spectra of the lignin fraction revealed that the presence of both guaiacyl and syringyl units, as well as p -hydroxyphenyl structures. Small amounts of esterified p -coumaric acids and mainly etherified ferulic acids were also identified in the lignin fractions. It was found that the lignin fractions obtained from the two different grasses had very similar structural composition. They are distinguished by rather low amounts of β- O -4 structures, resinol units (β-β), and of condensed units (β-5 and 5-5). This trait is even more pronounced in the production of phenolic compounds for chemical industry from grass.

Mycobacterium tuberculosis, the causative agent of tuberculosis, is on the rise again in step with the HIV/AIDS pandemic. Characteristically, M. tuberculosis features a hydrophobic cell envelope conferring resistance to degradation by host defences and impeding drug entry. This review focuses on mycolic acids, the distinctive cornerstone lipids of that cell envelope. The structure of these α-alkyl-β-hydroxy fatty acids is discussed along with their relation to pathogenicity. From the uniqueness of their structures and biosynthesis, rationales to target enzyme complexes involved in mycolic acid biosynthesis are discussed. The uniqueness of mycolic acids is also the basis of their application for immunodiagnosis of tuberculosis, an application showing renewed promise. Finally, emerging insights into the role of mycolic acids in the host–pathogen interaction are discussed, ascribing to mycolic acids a function in promoting cellular immune defences but also immune tolerance and the formation of foam macrophages.

One water-soluble and four alkali-soluble hemicellulosic preparations from perennial ryegrass leaves were comparatively studied, and their chemical composition, structural features, and physicochemical properties were examined. The relative monosaccharide compositions of the hemicelluloses were determined by high performance anion exchange chromatography after acid hydroloysis. 13 C NMR and FT-IR spectroscopic methods gave details of the anomeric linkage configuration and confirmed the structure of the hemicelluloses. The results showed that the water-soluble hemicelluloses probably consist of galactoarabinoxylans, β-glucan, and noticeable amounts of pectic polysaccharides, which had a lower molecular weight (19,360 g mol −1 ), while the four alkali-soluble hemicellulosic preparations are presumably composed of galactoarabinoxylans, l -arabino (4- O -methyl- d -glucurono)xylans, and β-glucan, which had higher molecular weights between 31,060 and 36,140 g mol −1 . Galactoarabinoxylans constitute a major fraction of both water- and two alkali-soluble hemicelluloses H 2 and H 3 , isolated with a higher concentration of alkali for a shorter period (18% NaOH or 18% KOH at 22 °C for 2 h). They consist of a linear β-(1 → 4) linked xylan backbone to which α- l -arabinofuranose units and/or short chains of sugar residues containing arabinose and galactose are attached as side residues via α-(1 → 3) and/or α-(1 → 2) linkages. On the other hand, the other two alkali-soluble hemicellulosic preparations H 4 and H 5 , extracted with a relatively lower concentration of alkali for a longer period (10% NaOH or 10% KOH at 22 °C for 16 h), mainly comprised l -arabino (4- O -methyl- d -glucurono)xylans, in which the β-(1 → 4) linked xylan backbone is substituted in O-3 and/or O-2 by signal α- l -arabinose residue and α- d -glucuronic acid or 4- O -methyl-glucuronic acid. β-Glucan, both in water- and alkali-soluble hemicelluloses, was characterized as linear homopolymers consisting of both β-(1 → 3) and β-(1 → 4) glucosidic linkages.

Similar to humans, bottlenose dolphins (Tursiops truncatus) can develop metabolic syndrome and associated high ferritin. While fish and fish-based fatty acids may protect against metabolic syndrome in humans, findings have been inconsistent. To assess potential protective factors against metabolic syndrome related to fish diets, fatty acids were compared between two dolphin populations with higher (n = 30, Group A) and lower (n = 19, Group B) mean insulin (11 ± 12 and 2 ± 5 μIU/ml, respectively; P < 0.0001) and their dietary fish. In addition to higher insulin, triglycerides, and ferritin, Group A had lower percent serum heptadecanoic acid (C17:0) compared to Group B (0.3 ± 0.1 and 1.3 ± 0.4%, respectively; P < 0.0001). Using multivariate stepwise regression, higher percent serum C17:0, a saturated fat found in dairy fat, rye, and some fish, was an independent predictor of lower insulin in dolphins. Capelin, a common dietary fish for Group A, had no detectable C17:0, while pinfish and mullet, common in Group B’s diet, had C17:0 (41 and 67 mg/100g, respectively). When a modified diet adding 25% pinfish and/or mullet was fed to six Group A dolphins over 24 weeks (increasing the average daily dietary C17:0 intake from 400 to 1700 mg), C17:0 serum levels increased, high ferritin decreased, and blood-based metabolic syndrome indices normalized toward reference levels. These effects were not found in four reference dolphins. Further, higher total serum C17:0 was an independent and linear predictor of lower ferritin in dolphins in Group B dolphins. Among off the shelf dairy products tested, butter had the highest C17:0 (423mg/100g); nonfat dairy products had no detectable C17:0. We hypothesize that humans’ movement away from diets with potentially beneficial saturated fatty acid C17:0, including whole fat dairy products, could be a contributor to widespread low C17:0 levels, higher ferritin, and metabolic syndrome.

Three stereoisomers of a wax ester meromycolate have been prepared starting from mannitol. A detailed comparison of their NMR spectra with those reported for a homologous series of natural wax esters allows the relative configurations of the α-methyl group and adjacent trans-cyclopropane to be determined.

Periploca sepium, Salix psammophila and Tamarix spp. make up an important part of the local vegetation in the sandland of China. This paper described a novel method on modification of the three shrub fibers as oil sorbents. Natural and modified fibers were chemically studied by non-destructive methods, infrared spectroscopy (IR) and cross-polarization nuclear magnetic resonance (CP-MAS 13C-NMR). The results show that during the reaction with acetic anhydride under mild conditions, the use of N-bromoscciniamide (NBS) catalyst resulted in a high weight percent gain (WPG). The acetylation of P. sepium fiber gave rise to the highest WPG (20.0%) compared with S. psammophila and Tamarix spp. fiber. IR and CP-MAS 13C-NMR analysis elaborates the chemical features of natural and acetylated willow fiber in detail.

We report the synthesis of a single enantiomer of an α-methyl-trans-cyclopropane unit present in a number of mycolic acids and its incorporation into a reported 1,2-dialkylcyclopropane meromycolate that contains one cis-1,2-dialkylcyclopropane and one α-methyl-trans-1,2-dialkylcyclopropane.

Dewaxed wheat straw was treated with acetic acid–H 2 O (65/35, v/v), acetic acid–H 2 O (80/20, v/v), acetic acid–H 2 O (90/10, v/v), formic acid–acetic acid–H 2 O (20/60/20, v/v/v), formic acid–acetic acid–H 2 O (30/60/10, v/v/v), methanol–H 2 O (60/40, v/v) and ethanol–H 2 O (60/40, v/v) using 0.1% HCl as a catalyst at 85 °C for 4 h, in which 78.2, 80.0, 88.2, 89.4, 94.1, 23.5 and 37.4% of the original lignin, and 42.4, 58.7, 70.0, 65.1, 76.5, 14.2 and 22.2% of the original hemicelluloses was released, respectively. Lignins obtained were characterized by their content of hemicelluloses, composition of phenolic acids and aldehydes, molecular weight, thermal stability and by UV, Fourier transform infrared (FT-IR), 1 H and 13 C nuclear magnetic resonance (NMR) spectroscopy. The results showed that aqueous organic acid was more effective than aqueous organic alcohol for extensive delignification and selective fractionation of cellulose, lignin and hemicelluloses from the straw. In particular, the addition of formic acid gave a significant effect on the dissolution of lignin. All the acid-insoluble lignin fractions contained small amounts of contaminated hemicelluloses as shown by their content of neutral sugars, 0.9–4.3%, and had weight-average molecular weight between 3960 and 4340 g mol −1 . An increase in concentration of acetic acid or formic acid in organosolv resulted in an increment in release of guaiacyl units and in lignin condensation. However, the lignin preparations released during the treatment with aqueous organic alcohol without organic acid contained almost equal amounts of non-condensed guaiacyl and syringyl units with fewer p -hydroxyphenyl units. The β-O-4 ether bonds together with β-β, β-5 and 5-5′ carbon–carbon linkages were identified to be present in lignin substructures.

We report a synthesis of a single enantiomer of a mycolic acid from Mycobacterium tuberculosis containing a di-cis-cyclopropane. The method can be simply varied to modify the chain lengths or the absolute stereochemistry of either cyclopropane.

The fractionation of wheat straw was studied using a two-stage process based on a steam explosion pre-treatment followed by alkaline peroxide post-treatment. Straw was steamed at temperatures comprised between 200 °C for 10 and 33 min and 220 °C for 3, 5, and 8 min. The steamed straw was washed with water to yield a solution rich in hemicelluloses-derived mono- and oligosaccharides (20.5–28.5%) together with small amounts of degraded hemicellulosic polymers (2.4–6.2%) and minor quantities of lignin (1.9–2.1%). The washed fibre was post-treated by 2% alkaline peroxide (pH 11.5) at 50 °C for 5 h. The alkali-soluble lignin (13.7–15.0%) and hemicelluloses (8.4–13.3%) were recovered by precipitation. The post-treatment was sufficient to remove lignin and survived hemicellulosic polymers and increase the brightness of the exploded straw significantly. The two-stage treatments together degraded 77.0–87.6 of the total original hemicelluloses and 92.3–99.4% of the total original lignin. This paper examined these two groups of six hemicellulosic polymer preparations degraded during the various steam explosion pre-treatments (H1a–6a) and released during the sequential alkaline peroxide post-treatment (H1b–6b). The effect of the most important variables in steam explosion pre-treatment (temperature, residence time, and water to straw ratio) on physico-chemical properties and structural features of the degraded hemicellulosic polymers were investigated. Thermoanalysis of these degraded hemicellulosic polymer fractions indicated that hemicellulose degradation products were also condensed to form more thermostable substrates during the steam explosion.

Original lignin and hemicelluloses were sequentially extracted with high yield/purity, using acidic dioxane/water solution and dimethyl sulfoxide, from ball-milled wheat straw. The acidic dioxane lignin fraction is distinguished by high beta-O-4' structures and by low amounts of condensed units (beta-5', 5-5', and beta-1'). Hemicelluloses contain arabinoxylans as the major polysaccharides, which are substituted by alpha-l-arabinofuranose, 4-O-methylglucuronic acid, acetyl group (DS = 0.1), and xylose at O-3 and/or O-2 of xylans. It was found that arabinoxylans form cross-links with lignins through ferulates via ether bonds, glucuronic acid via ester bonds, and arbinose/xylose via both ether and glycosidic bonds, respectively, in the cell walls of wheat straw. Diferulates are also incorporated into cross-links between lignin and hemicelluloses as well as lignification of wheat straw cell walls. The guaiacyl unit is considered to be a significant condensed structural constructor in extracted lignin and a connector between lignin and carbohydrates.

The isolation of cellulose from wheat straw was studied using a two-stage process based on steam explosion pre-treatment followed by alkaline peroxide post-treatment. Straw was steamed at 200 degrees C, 15 bar for 10 and 33 min, and 220 degrees C, 22 bar for 3, 5 and 8 min with a solid to liquid ratio of 2:1 (w/w) and 220 degrees C, 22 bar for 5 min with a solid to liquid ratio of 10:1, respectively. The steamed straw was washed with hot water to yield a solution rich in hemicelluloses-derived mono- and oligosaccharides and gave 61.3%, 60.2%, 66.2%, 63.1%, 60.3% and 61.3% of the straw residue, respectively. The washed fibre was delignified and bleached by 2% H2O2 at 50 degrees C for 5 h under pH 11.5, which yielded 34.9%, 32.6%, 40.0%, 36.9%, 30.9% and 36.1% (% dry wheat straw) of the cellulose preparation, respectively. The optimum cellulose yield (40.0%) was obtained when the steam explosion pre-treatment was performed at 220 degrees C, 22 bar for 3 min with a solid to liquid ratio of 2:1, in which the cellulose fraction obtained had a viscosity average degree of polymerisation of 587 and contained 14.6% hemicelluloses and 1.2% klason lignin. The steam explosion pre-treatment led to a significant loss in hemicelluloses and alkaline peroxide post-treatment resulted in substantial dissolution of lignin and an increase in cellulose crystallinity. The six isolated cellulose samples were further characterised by FT-IR and 13C-CP/MAS NMR spectroscopy and thermal analysis.

Two groups of six lignin preparations degraded during various steam-explosion pre-treatments (L1a–6a) and released during the sequential alkaline peroxide post-treatment (L1b–6b) were isolated and characterised. The steam pre-treatment and alkaline peroxide post-treatment, respectively, resulted in a degradation of 11.2–12.4% and 80.6–87.6% of the original lignin, which together removed 92.4–99.4% of the original lignin from wheat straw. L1b–6b lignin fractions with a sugar content lower than 1.5% were obtained after alkaline peroxide post-treatment of the corresponding steam exploded straw, whereas the lignin fractions L1a–6a degraded during the steam pre-treatment, contained two to three times higher sugars on the basis of the dry weight of the lignin. The weight-average molecular weight (Mw) of the L1a–6a lignin preparations ranged between 3460 and 3870 g mol−1 with polydispersity of 1.4–2.0, whereas the Mw and Mw/Mn of the L1b–6b lignin fractions released during the alkaline peroxide post-treatment, corresponded to 4270–4640 g mol−1 and 1.8–2.1, respectively. The L1a–6a lignin preparations were shown to be more condensed and thermally stable than the L1b–6b lignin fractions. FT-IR and 1H and 13C NMR analyses showed that the steam pre-treatment under the conditions given led to a comprehensive cleavage of β-O-4 ether bonds, condensation reactions, and a certain demethylation of aromatic methoxyl groups in lignin structure. This is particularly true for the L1a–6a lignin fractions degraded during the steam-explosion pre-treatment.

The effects of substitution of X=C by Si or Ge in X(CH3)3 moieties attached to the formal double bond of 3,3-dimethylcyclopropene are examined. Regularities in observed trends of vibrational frequencies implicating the moieties containing the X atom, as the X atomic mass is increased, are extrapolated to X=Sn. The results of this extrapolation made it possible to assign the known experimental vibrational frequencies of 3,3-dimethyl-1-(trimethylstannyl)cyclopropene and 3,3-dimethyl-1,2-bis(trimethylstannyl)cyclopropene.

Lignin preparation with high yield (85.71%) and purity (96.97%) from wheat straw was obtained by ball milling treatment and direct acidic dioxane extraction. This procedure gives a material that is representative of the whole lignin of wheat straw. The lignin fraction is distinguished by high β-O-4′ structures and small amounts of condensed units (β-5′, 5-5′, and β-1′) enriched in guaiacyl units. p-Coumaric acid is linked to lignin via γ-ester bond and a few ether bonds such as β-O-4′, whereas ferulic acid is linked to lignin by ether bonds, and its dehydrodimers (5-5′/8-O-4′) are also incorporated into lignin polymer.

Oxidation of gem -dibromocyclopropanes with chromium trioxide in acetic acid or a number of other reagents is generally slower than that of the corresponding cyclopropane; in a number of cases moderate yields of products are obtained but these show unexpected oxidation patterns.

Seven wheat straw cellulose preparations were isolated by a two-stage acidic organosolv treatment followed by cyanamide activated hydrogen peroxide bleaching. The effects of concentration of acetic and formic acids on the yield of cellulose and degradation of lignin and non-cellulose polysaccharides were investigated. Organic acids were more effective than alcohols on the degradation of lignin and hemicelluloses. Formic acid/acetic acid/water (30/60/10, v/v/v) system was found to be the most effective in delignification and removal of non-cellulose polysaccharides from the straw and did not have any undesirable effects on cellulose properties such as its intrinsic viscosity. In this case, the treatment removed 94.1% of the original lignin and 76.5% of the original hemicelluloses using 0.1% HCl as a catalyst at 85 °C for 4 h. Cyanamide activated hydrogen peroxide bleaching degraded substantial amounts of residual hemicelluloses and lignin, produced the cellulose samples having a relatively high purity. Under a best condition, a cellulose relatively free of lignin (0.7%) and with intrinsic viscosity of 393 ml g −1 and favourable molar mass (213,940 g mol −1 ) was obtained. Both unbleached and bleached cellulose preparations were further characterised by FT-IR and CP/MAS 13 C NMR spectroscopy, and thermal stability.

3-(2 S -Heptylcycloprop-1 S -yl)propanoic acid 2-phenylethanamide was synthesised from cis -cyclopropan-1,2-dimethanol via enzymatic desymmetrisation of the dibutyrate; it gave identical NMR spectroscopic data to those reported for grenadamide but had an equal and opposite absolute rotation, indicating that the latter is the 2 R ,1 R -enantiomer.

Wheat straw lignin and hemicelluloses were degraded in a totally chlorine-free medium containing 80% acetic acid and 0.92–13.5% nitric acid. Effect of treatment time and temperature as well as nitric acid concentration on the efficiency of degradation of lignin and hemicellulosic polymers and on the yield of cellulose were comparatively investigated. The treatment with 80% acetic acid and 0.92% nitric acid as a catalyst at 120 °C for 20 min resulted in over 81% original hemicelluloses and 92% original lignin degradation. As the nitric acid concentration raises to 8.5%, over 96% original hemicelluloses and approximately 98% original lignin were degraded, yielding the cellulose approaching 96% purity. The characterisation of isolated cellulosic preparations was performed by their intrinsic viscosity, molecular weight, FT-IR, CP-MAS 13 C-NMR, and thermal studies. The results showed that the treatment using 80% acetic acid and nitric acid as a catalyst under the conditions given also resulted in somewhat acetylation of the cellulose and decreased the degree of crystallinity of cellulose except for significant degradation of lignin and hemicellulosic polymers. The thermal stability of the cellulose declined with a decrease in its intrinsic viscosity

Sequential treatments of dewaxed bagasse with distilled water, 0.5 M NaOH, 0.5, 1.0, 1.5, 2.0, and 3.0% H(2)O(2) at pH 11.5, and 2 M NaOH at 55 degrees C for 2 h solubilized 2.8, 52.5, 14.9, 3.3, 5.5, 5.0, 2.8, and 2.2% of the original lignin, respectively. The eight isolated lignin fractions were subjected to a comprehensive structural characterization by UV, FT-IR, and (1)H and (13)C NMR spectroscopies and thermal analysis. The nitrobenzene oxidation method was also applied to the in situ lignins. The seven lignin fractions, isolated successively with alkali and alkaline peroxide, were all SGH-type lignins, with a small amount of esterified p-coumaric acid and mainly etherified ferulic acid. No significant differences were found in the weight-average molecular weights (1680-2220 g/mol) of the seven alkali and alkaline peroxide dissolved lignins. However, the first four lignin fractions, isolated with 0.5 M NaOH and 0.5, 1.0, and 1.5% H(2)O(2) at pH 11.5, were rich in syringyl units and contained large amounts of noncondensed ether structures, whereas the last three lignin fractions, isolated sequentially with 2.0 and 3.0% H(2)O(2) at pH 11.5 and 2 M NaOH at 55 degrees C for 2 h, had a higher degree on condensation and were rich in guaiacyl lignins.

(11R,12S)-Lactobacillic acid has been prepared from 2,3-O-isopropylidene-d-glyceraldehyde, in a sequence involving asymmetric cyclopropanation, and from cis-cyclopropane-1,2-dimethanol, using enzymatic desymmetrisation. The key step in the former route was the stereochemically controlled cyclopropanation of (1Z,4′S)-(2′,2′-dimethyl-1′,3′-dioxolan-4′-yl)-1-octene via a Simmons–Smith type reaction, using diethylzinc and chloroiodomethane. This product was converted into the key intermediate (1R,2S)-1-formyl-2-hexylcyclopropane, which was also obtained by a known sequence from the (1R,2S)-monobutyrate ester of cis-cyclopropane-1,2-dimethanol. This pivotal aldehyde was converted into (11R,12S)-lactobacillic acid. Using analogous chemistry, the (11S,12R)-enantiomer of lactobacillic acid was prepared from 2,3-O-isopropylidene-d-glyceraldehyde or from the (1S,R)-monobutyrate ester of cis-cyclopropane-1,2-dimethanol.

This review surveys both data obtained by the authors and published data on the partial or full hydrodehalogenation of di- and polyhalocyclopropanes (chlorides and bromides) with Grignard reagents catalyzed by titanium or zirconium compounds. The factors affecting the efficiency and selectivity of the hydrodebromination of bromocyclopropanes are considered: the nature of Grignard reagents (including isotopically labeled reagents), their transformations and effects in catalyzed and uncatalyzed reactions, the participation of solvents, catalytic and stoichiometric amounts of the catalyst, etc. A scheme is proposed in which the key steps of the mechanism of hydrodebromination of bromocyclopropanes includes three blocks of reactions: (a) the generation of a catalytically active Ti(II) species; (b) the hydrodehalogenation of bromocyclopropanes involving electron transfer from a low-valent catalyst species, formation of the cyclopropyl radical, and stabilization of this radical as a result of hydrogen atom transfer from the solvent molecule; and (c) transformations of previously formed radical species, such as dimerization and disproportionation (for example, of radical species generated from Grignard reagents or ether molecules) or the linking of alkyl radicals to radical species produced from solvent molecules.

During growth of Pseudomonas putida strain TW3 on 4-nitrotoluene (4NT) or its metabolite 4-nitrobenzoate (4NB), the culture medium gradually becomes yellow-orange with a λ max of 446 nm. The compound producing this color has been isolated and identified as a new phenoxazinone, 2-aminophenoxazin-3-one-7-carboxylate (APOC). This compound is formed more rapidly and in greater quantity when 4-amino-3-hydroxybenzoate (4A3HB) is added to growing cultures of strain TW3 and is also formed nonbiologically when 4A3HB is shaken in mineral salts medium but not in distilled water. It is postulated that APOC is formed by the oxidative dimerization of 4A3HB, although 4A3HB has not been reported to be a metabolite of 4NT or a product of 4NB catabolism by strain TW3. Using the cloned pnb structural genes from TW3, we demonstrated that the formation of the phenoxazinone requires 4-hydroxylaminobenzoate lyase (PnbB) activity, which converts 4-hydroxylaminobenzoate (4HAB) to 3,4-dihydroxybenzoate (protocatechuate) and that 4-nitrobenzoate reductase (PnbA) activity, which causes the accumulation of 4HAB from 4NB, does not on its own result in the formation of APOC. This rules out the possibility that 4A3HB is formed abiotically from 4HAB by a Bamberger rearrangement but suggests that PnbB first acts to effect a Bamberger-like rearrangement of 4HAB to 4A3HB followed by the replacement of the 4-amino group by a hydroxyl to form protocatechuate and that the phenoxazinone is produced as a result of some misrouting of the intermediate 4A3HB from its active site.

Reaction of gem -dibromocyclopropanes with ethylmagnesium bromide at ambient temperature leads to very high yields of allenes; when cyclopropylidene–allene ring opening is suppressed, alternative carbenic products are observed, although other reactions compete. When the reactions are carried out at −60°C, a 1-bromo-1-(bromomagnesio)-cyclopropane is formed which may be trapped by a number of electrophiles.

(1S,2S)-2[(S)-Amino(4-methoxyphenyl)methyl]cyclopropan-1-ol together with a range of racemic 2-(2-aminoalkyl)-1-hydroxycyclopropanes were prepared by a stepwise procedure involving a 1,3-dipolar cycloaddition of a nitrile oxide to a cyclopropene followed by reduction of the derived bicycle.

Reaction of 2-acylaminomethyl-1,1-dibromocyclopropanes with methyllithium at −90°C leads to selective bromine-lithium exchange and cyclisation to give a 1-bromo-3-azabicyclo[3.1.0]hexan-2-ol.

Furfural residue (FR), composed mainly of cellulose and lignin, is an industrial waste produced during furfural manufacture. In this study, dioxane, alkali, ethanol, alkali-ethanol, and alkaline hydrogen peroxide (AHP) were used to extract lignins from FR. The structural features of these lignins obtained were characterized by sugar analysis, GPC, UV, FT-IR, and HSQC spectra. As compared to dioxane lignin (DL), other lignins showed lower molecular weights (Mw) owing to the partial cleavage of the linkages between lignin units. Results from HSQC spectra revealed that β-O-4' and β-5' were still the major linkages of the FR lignin. Moreover, p-coumaric and ferulic acids were released and co-precipitated in the lignin preparations extracted with alkali and AHP, whereas part of the esters in DL were preserved during the dioxane extraction. Antioxidant activity investigation indicated that the antioxidant property of the alkali and alkali-ethanol lignins was higher than that of the commercial antioxidant, butylated hydroxytoluene.

Consumption of the bracken fern Pteridium aquilinum by cattle has been shown to induce bladder and intestinal carcinomas in cattle and to cause a number of diseases in other farm animals. An unstable glucoside named ptaquiloside, containing a reactive cyclopropane ring, has been isolated from the fern and its potent carcinogenicity proven. Nineteen of 31 ferns tested by chemotaxonomic methods in Japan have been found to contain potentially carcinogenic ptaquilosides as have Cheilanthes sieberi and Pteridium esculentum. Hydrolysis of ptaquilosides leads to pterosins; under milder conditions a dienone which is believed to be the primary carcinogen is obtained. Hypacrone, a sesquiterpine containing a reactive cyclopropane ring, has been isolated from Hypolepis punctata and its structure proved by synthesis. Illudins, structurally similar to ptaquiloside, have been isolated from the basidiomycete Omphalotus illudens. These give anti-tumour activity and similar reactivity with nucleophiles to ptaquiloside. Compound CC-1065, a highly toxic antibiotic also containing a cyclopropane ring, has been isolated from Streptomyces zelensis. The mechanism of its reactivity with DNA has been compared to that of ptaquiloside and the small structural differences between carcinogenic and anti-tumour activity discussed. Both CC-1065 and adozelesin, a synthetic analogue with anti-tumour activity, have been shown to alkylate the N-3 atom of adenine in a certain sequence of DNA. The reactivity of cysteine with ptaquilosides and illudins is discussed, as is the role of cysteine alkylating agents in apoptosis. © 2000 Cancer Research Campaign

3-Oxa-2,4-dioxobicyclo[3.1.0]hexane provides a flexible starting material for the preparation of single enantiomers of a meromycolic acid, a long chain fatty acid containing two remote cis-cyclopropanes.

A number of 1- and 1,2-disubstituted cyclopropenes undergo [4+2]-cycloaddition to methyl vinyl ketone or acrolein at ambient temperature to produce 2-oxabicyclo[4.1.0]hept-3-enes. When 1-phenyl-2-trimethylsilyl-cyclopropene is treated with 0.4 mol. equiv. of m-chloroperbenzoic acid, the derived ring-opened enone undergoes [4+2]-cycloaddition to the remaining starting material at ambient temperature.