Microbial transformations of flavanone by Aspergillus niger and Penicillium chermesinum cultures

As a result of biotransformation of flavanone (1) by the strain Aspergillus niger MB (being the UV mutant) and by the wild strain Penicillium chermesinum 113 the products of hydroxylation at C-6 (2) and C-4′ (5) were obtained. Additionally, three dihydrochalcones with hydroxyl groups at C-2′ (4), C-2′ and C-5′ (3) and C-2′ and C-4 (6) were formed.     

Different biosynthetic pathways of the pyrimidine moiety of thiamin in procaryotes and eucaryotes

[¹⁴C]Formate is incorporated into the C-2 of the pyrimidine moiety of thiamin by Escherichia coli and Salmonella typhimurium. In Saccharomyces cerevisiae, it is incorporated into C-4. Radioactive carbons of [1-¹⁴C]glycine and [2-¹⁴C]glycine are incorporated by S. typhimurium into the C-4 and C-6 of the pyrimidine, respectively, but not by S. cerevisiae. These facts suggest that procaryotes and eucaryotes have different biosynthetic pathways for pyrimidine. In this study, the procaryotes tested incorporated [¹⁴C]formate into the C-2 and the eucaryotes incorporated it into the C-4 of the pyrimidine.     

Structure-Activity Relationships of Abscisic Acid Analogs Based on the Induction of Freezing Tolerance in Bromegrass (Bromus inermis Leyss) Cell Cultures

The induction of freezing tolerance in bromegrass (Bromus inermis Leyss) cell culture was used to investigate the activity of absisic acid (ABA) analogs. Analogs were either part of an array of 32 derived from systematic alterations to four regions of the ABA molecule or related, pure optical isomers. Alterations were made to the functional group at C-1 (acid replaced with methyl ester, aldehyde, or alcohol), the configuration at C-2, C-3 (cis double bond replaced with trans double bond), the bond order at C-4, C-5 (trans double bond replaced with a triple bond), and ring saturation (C-2′, C-3′ double bond replaced with a single bond so that the C-2′ methyl and side chain were cis). All deviations in structure from ABA reduced activity. A cis C-2, C-3 double bond was the only substituent absolutely required for activity. Overall, acids and esters were more active than aldehydes and alcohols, cyclohexenones were more active than cyclohexanones, and dienoic and acetylenic analogs were equally active. The activity associated with any one substituent was, however, markedly influenced by the presence of other substituents. cis, trans analogs were more active than their corresponding acetylenic analogs unless the C-1 was an ester. Cyclohexenones were more active than cyclohexanones regardless of oxidation level at C-1. An acetylenic side chain decreased the activity of cyclohexenones but increased the activity of cyclohexanones relative to their cis, trans counterparts. Trends suggested that for activity the configuration at C-1′ has to be the same as in (S)-ABA, in dihydro analogs the C-2′-methyl and the side chain must be cis, small positional changes of the 7′-methyl are tolerable, and the C-1 has to be at the acid oxidation level.     

Flavonoids and Isoflavonoids of Millettia dura and Millettia ferruginea: Phytochemical review and chemotaxonomic values

The phytochemical information on Millettia dura Dunn, M. ferruginea (Hochst.) Baker and M. ferruginea subsp. darassana (Cufod.) J.B. Gillett was reviewed. All the three taxa elaborate mainly isoflavones (33 reported), occurring in the flowers, seeds/seed pods, stem bark and root bark. Out of the 33 isoflavones reported, some 19 (ca. 58%) contain prenyl at C-8 or its modification as 2,2-dimethylchromene ring at C-7/C-8, occurring in all the three taxa. Except for three isoflavones isolated from M. ferruginea subsp. darassana, all the isoflavones of these taxa are 5-deoxygenated. In these taxa, oxygenation at C-6 is a common feature, while isoflavones with C-8 oxygenation are rare, only three reported, and all of these from M. dura. There are 7 rotenoids reported from these taxa, and occur almost entirely in the seeds/seedpods of these plants. The major rotenoid with methylenedioxy group at C-2/C-3, millettone and its 12a-hydroxy derivative, millettosine, occur only in M. dura, this appears to distinguish M. dura from M. ferruginea.     

Association between the interleukin-4, interleukin-13 polymorphisms and asthma: a meta-analysis

A numbers studies had been reported that the polymorphisms in the Interleukin 4 (IL-4) and Interleukin 13 (IL-13) genes were associated with susceptibility to asthma. However, the results were inconsistent and inconclusive. We carried out a meta-analysis of case–control genetic association studies to assess whether the combined data showed this association by using a genetic model-free approach. Thirty studies (total 12,781 asthma and 11,500 controls) for the IL-4 C-33T and C-589T, IL-13 C-1112T and G+2044A with asthma were included in the meta-analysis. The results indicated that there were an association between the IL-4 C-33T (P = 0.006) and C-589T (P = 0.04), IL-13 C-1112T (P = 0.002) and G+2044A (P = 0.04) and susceptibility to asthma. And the definition of asthma subgroup meta-analysis demonstrates that the IL-4 C-33T is not associated with nonatopic or atopic, and IL-4 C-589T and IL-13 C-1112T polymorphisms are not associated with atopic. In the ethnicity subgroup meta-analysis, the IL-4 ?589T (P = 0.003) and the IL-13 ?1112T (P < 0.00001) alleles are associated with asthma among Caucasian, but not on the IL-13 +2044A allele. In conclusion, IL-4 C-33T and C-589T, IL-13 C-1112T and G+2044A could be proposed as asthma susceptible SNPs. Further investigation in larger studies and meta-analysis is required.     

The conformation of 2,3,4-tri-O-acetyl-D-xylono-l,5-lactone

A conformational analysis of 2,3,4-tri-O-acetyl-D-xylono-1,5-lactone (5) has been performed by using ¹H-n.m.r. spectral data. Evidence is presented that the C-3 and C-4 acetoxyl groups are anti-periplanar. The possible contribution of attractive 1,3- and 1,4-interactions between the electropositive lactone-ring oxygen and the endo-acetoxyl groups at C-3 and C-4 to the conformational stability of 5 is discussed.     

Genomic insight into Chryseobacterium turcicum sp. nov. and Chryseobacterium muglaense sp. nov. isolated from farmed rainbow trout in Turkey

Four strains, designated as C-2, C-17^T, C-39^T and Ch-15, were isolated from farmed rainbow trout samples showing clinical signs during an investigation for a fish-health screening study. The pairwise 16S rRNA gene sequence analysis showed that strain C-17^T shared the highest identity level of 98.1 % with the type strain of Chryseobacterium piscium LMG 23089^T while strains C-2, C-39^T and Ch-15 were closely related to Chryseobacterium balustinum DSM 16775^T with an identity level of 99.3 %. A polyphasic approach involving phenotypic, chemotaxonomic and genome-based analyses was employed to determine the taxonomic provenance of the strains. The overall genome relatedness indices including dDDH and ANI analyses confirmed that strains C-2, C-17^T, C-39^T and Ch-15 formed two novel species within the genus Chryseobacterium. Chemotaxonomic analyses showed that strains C-17^T and C-39^T have typical characteristics of the genus Chryseobacterium by having phosphatidylethanolamine in their polar lipid profile, MK-6 as only isoprenoid quinone and the presence of iso-C_15:0 as major fatty acid. The genome size and G + C content of the strains ranged between 4.4 and 5.0 Mb and 33.5 – 33.6 %, respectively. Comprehensive genome analyses revealed that the strains have antimicrobial resistance genes, prophages and horizontally acquired genes in addition to secondary metabolite-coding gene clusters. In conclusion, based on the polyphasic analyses conducted on the present study, strains C-17^T and C-39^T are representatives of two novel species within the genus Chryseobacterium, for which the names Chryseobacterium turcicum sp. nov. and Chryseobacterium muglaense sp. nov. with the type strains C-17^T (=JCM 34190^T = KCTC 82250^T) and C-39^T (=JCM 34191^T = KCTC 822251^T), respectively, are proposed.     

Bile salts of vertebrates: structural variation and possible evolutionary significance

Biliary bile salt composition of 677 vertebrate species (103 fish, 130 reptiles, 271 birds, 173 mammals) was determined. Bile salts were of three types: C₂₇ bile alcohols, C₂₇ bile acids, or C₂₄ bile acids, with default hydroxylation at C-3 and C-7. C₂₇ bile alcohols dominated in early evolving fish and amphibians; C₂₇ bile acids, in reptiles and early evolving birds. C₂₄ bile acids were present in all vertebrate classes, often with C₂₇ alcohols or with C₂₇ acids, indicating two evolutionary pathways from C₂₇ bile alcohols to C₂₄ bile acids: a) a ‘direct’ pathway and b) an ‘indirect’ pathway with C₂₇ bile acids as intermediates. Hydroxylation at C-12 occurred in all orders and at C-16 in snakes and birds. Minor hydroxylation sites were C-1, C-2, C-5, C-6, and C-15. Side chain hydroxylation in C₂₇ bile salts occurred at C-22, C-24, C-25, and C-26, and in C₂₄ bile acids, at C-23 (snakes, birds, and pinnipeds). Unexpected was the presence of C₂₇ bile alcohols in four early evolving mammals. Bile salt composition showed significant variation between orders but not between families, genera, or species. Bile salt composition is a biochemical trait providing clues to evolutionary relationships, complementing anatomical and genetic analyses.     

X-ray crystal,and molecular,structure of 1,2,3-tri-O-acetyl-4,5-dideoxy-4-C-[(R)-phenylphosphinyl]-α-l-lyxofuranose: The first x-ray analysis of a pentofuranose having phosphorus in the hemiacetal ring

X-Ray crystallographic analysis was performed on the compound to which had been assigned the structure of 1,2,3-tri-O-acetyl-4,5-dideoxy-4-C-[(R)-phenylphosphinyl]-α-l-lyxofuranose. The results showed that the compound has the proposed configuration, the five-membered ring is in the E₃ conformation, with a tendency towards the ³T₂ form, the substituents at P-5 and C-5 are linked bisectionally, the acetoxyl group at C-2 and the methyl group at C-4 are linked quasiequatorially, and the acetoxyl group at C-3 is linked axially.     

Crystal structure of methyl 2,6-dichloro-2,6-dideoxy-3,4-O-isopropylidene-α-D-altropyranoside. A pyranoside system close to a skew-boat conformation

The crystal structure of methyl 2,6-dichloro-2,6-dideoxy-3,4-O-isopropylidene-α-D-altropyranoside (1) has been determined by X-ray diffraction. The compound crystallizes in the orthorhombic system, space group P2₁2₁2₁, with unit-cell dimensions a  7.932, b  8.133, and c  20.447 Å. The structure was solved by the heavy-atom method and refined by the least-squares technique to an R value of 0.047 by using 736 intensities measured on a diffractometer. The pyranoside ring is close to a skew-boat conformation, with C-2 and C-5 being maximally displaced from the least-squares plane through the remaining four atoms. The H-1H-2 dihedral angle of  158° is in agreement with the J_1,2 value of 4.5 Hz. Thus the solid-state conformation appears to correspond with the conformation in solution. The dioxolane ring is in a twist form, with O-4 and, C-8 puckered on opposite sides of the plane of the other ring atoms. The pyranose-ring substituents are in equatorial and pseudoequatorial orientations. The hydrogen atoms at C-3 and C-4 are in a cis arrangement. The orientations of both the methoxyl group and the chloromethyl group with respect to the ring are gauche—trans. The exocyclic anomeric C-1O-1 bond-distance (1.39 Å) is the shortest CO bond in the structure. The intracyclic CO bonds are significantly different, C-1O-5 being less than C-5O-5.     

Vieloplains A-G,seven new guaiane-type sesquiterpenoid dimers from Xylopia vielana

Seven new guaiane-type sesquiterpene dimers vieloplains A-G, connecting patterns through three different direct CC bonds compounds 1–5 (C-3 to C-3′, C-4 to C-1′), compound 6 (C-2 to C-3′, C-4 to C-2′) and compound 7 (C-2 to C-1′, C-4 to C-2′) were isolated from the roots of Xylopia vielana. Their absolute configurations were established by NOESY analysis, the Cu Kα X-ray crystallographic the experiment circular dichroism (ECD) and the calculated ECD. Among them, only compound 6 showed a considerable cytotoxicity against DU145 cells with IC₅₀ values of 9.5 μM. Flow cytometry analysis confirmed that 6 caused death of DU145 cells via apoptosis induction.     

Etude cristallographique des β-d-glucopyranosyl- et β-d-mannopyranosyl-benzènes acétylés,analogues de nucléosides pyrimidiques

The structures of the two title C-glycopyranosylarene nucleosides have been determined by X-ray diffraction. The aim of this work was to relate the conformation around the extracyclic C-1C-7 bond to steric hindrance between the pyranose and benzene rings. The torsion angles observed in the two compounds (O-5C-1C-7C-8: +61,7° for 1, ?13,4° for 2) signify of a C-2 configurational modification. Moreover, the interaction between O-5 and an o-phenyl hydrogen could explain the particular conformation of the aryl substituent in 2.     

Conversion of ecdysone and 20-hydroxyecdysone into 3-dehydroecdysteroids is a major pathway in third instar Drosophila melanogaster larvae

Ecdysone and 20-hydroxyecdysone metabolism was investigated in third instar Drosophila larvae both in vivo by injecting radiolabelled ecdysteroids and in vitro by incubating various tissues with labelled ecdysteroids.Ecdysone metabolism proceeds through different pathways: (1) C-20 hydroxylation; (2) C-26 hydroxylation and C-26 oxidation leading to the formation of 26-hydroxyecdysteroids (26-hydroxyecdysone and 20,26-dihydroxyecdysone) and acidic compounds (ecdysonoic acid and 20-hydroxyecdysonoic acid); C-3 oxidation and C-3 epimerization then conjugation leading to the formation of 3-dehydrocompounds (3-dehydroecdysone and 3-dehydro-20-hydroxyecdysone), 3-epimers (3-epiecdysone and 3-epi-20-hydroxyecdysone) and conjugates (only one conjugate was tentatively characterized as 3-epi-20-hydroxyecdysone-3-phosphate). 3-Dehydrocompounds are the major metabolites formed in third instar Drosophila larvae and C-3 oxidation occurs in various tissues. Experiments using tritiated cholesterol provided evidence that 3-dehydroecdysone and 3-dehydro-20-hydroxyecdysone are true endogenous ecdysteroids in Drosophila larvae.     

Formation of α-Hydroxyglutaric Acid by Aspergillus glaucus

Aspergillus glaucus, cultured on sodium propionate-mineral salts medium, incorporates ¹⁴C-glyoxylate into labeled α-hydroxyglutaric acid within 30 sec. Mycelial extracts retain this biosynthetic capacity, which is destroyed by heating. Propionyl-2-¹⁴C-coenzyme A also in incorporated into labeled α-hydroxyglutaric acid by these mycelial extracts, but to a more limited extent. ¹⁴CO₂ evolution studies, employing differentially labeled ¹⁴C-propionate, indicate C-1 is oxidized by the mold before C-2, and C-2 before C-3. These findings suggest the involvement of α-hydroxyglutaric acid in the catabolism of propionic acid by A. glaucus.     

Design,synthesis, and pharmacological evaluation of N-(4-mono and 4,5-disubstituted thiazol-2-yl)-2-aryl-3-(tetrahydro-2H-pyran-4-yl)propanamides as glucokinase activators

A series of N-thiazole substituted arylacetamides were designed on the basis of metabolic mechanism of the aminothiazole fragment as glucokinase (GK) activators for the treatment of type 2 diabetes. Instead of introducing a substituent to block the metabolic sensitive C-5 position on the thiazole core directly, a wide variety of C-4 or both C-4 and C-5 substitutions were explored. Compound R-9k bearing an iso-propyl group as the C-4 substituent was found possessing the highest GK activation potency with an EC₅₀ of 0.026 μM. This compound significantly increased both glucose uptake and glycogen synthesis in rat primary cultured hepatocytes. Moreover, single oral administration of compound R-9k exerted significant reduction of blood glucose levels in both ICR and ob/ob mice. These promising results indicated that compound R-9k is a potent orally active GK activator, and is warranted for further investigation as a new anti-diabetic treatment.     

Biosynthesis of (+)-car-3-ene in Pinus species

Degradation of (+)-car-3-ene biosynthesized from MVA-[2-¹⁴C] in Pinus palustris or Pinus sylvestris proved that the C-4 atom of the monoterpene is derived from C-2 of MVA rather than C-4 as has been hitherto assumed. The pro-2S hydrogen of MVA is stereospecifically lost in the formation of the Δ³-double bond. These results delineate possible routes for the biosynthesis of the carane skeleton.     

Sterols of Mediterranean Florideophyceae

The distribution of sterols in 31 Mediterranean Florideophyceae has been investigated. Cholesterol is present in the greatest majority of the species examined, while the occurrence of other C-27 sterols (desmosterol, 22-dehydrocholesterol, liagosterol and cholest-7-en-3β-ol) is much more restricted. Two species (Rytiphloea tinctoria and Vidalia volubilis) contain, in addition to C-27 sterols, large amounts of C-28 and C-29 compounds.     

X-Ray crystal and molecular structure of 1,2,3,5-tetra-O-acetyl-4-deoxy-4-C-[(S)-ethylphosphinyl]-α-d-ribofuranose,and conformations of aldopentofuranose analogs having phosphorus in the hemiacetal ring

X-Ray crystallographic analysis was performed on the compound to which had been assigned the structure 1,2,3,5-tetra-O-acetyl-4-deoxy-4-C-[(S)-ethylphosphinyl]-α-d-ribofuranose. The results showed that the compound has the proposed configuration, the five-membered ring is in the ³T₂ conformation with a tendency towards the E₂ form, the substituents on C-1, C-4, and P-5 are linked bisectionally, and the acetoxyl groups on C-2 and C-3 are respectively attached axially and equatorially. Based on the X-ray crystallographic and ¹H-n.m.r.-spectral data, favored conformations of P-in-ring analogs of aldopentofuranose peracetates in solution are discussed.     

The incorporation of [5,6-13C2]Nicotinic acid into the tobacco alkaloids examined by the use of 13C nuclear magnetic resonance

[5,6-¹⁴C,¹³C₂]Nicotinic acid was prepared from [¹⁴C,¹³C]methyl iodide via nitromethane, 2-nitroacetaldehyde oxime, 3-nitroquinoline, 3-aminoquinoline, and quinoline in 20% overall yield. Administration of this material to Nicotiana tabacum and N. glauca afforded labeled anabasine, anatabine, nicotine, and nornicotine. Qualitative and quantitative incorporation (0.07–4.5% specific incorporation) was determined by radioactive assay and by examination of the ¹³C NMR spectra of these alkaloids. Satellites due to spin-spin coupling of the incorporated contiguous ¹³C atoms were observed at the resonances due to C-5 and C-6 in anabasine, nicotine, and nornicotine. In anatabine, satellites were found at C-5, C-6, C-5′, and C-6′.