(E)-9-Chloro-8-nonene-4,6-diyne-1,2,3-triol,an artefact from pneumatospora obcoronata

A hyphomycete, Exeter Herbarium Number 23000, was isolated in Malaysia from green leaves of the fruit tree Nephelium lappaceum (rambutan) and from fallen leaves of Hevea brasilienisis (rubber). The fungus was grown for five days in a malt extract medium. From the mycelial filtrate, a novel compound, (E)-9-chloro-8-nonene-4,6-diyne-1,2,3-triol, wasextracted.     

Alkaline and smith degradation of oxidized dermatan sulphate-chondroitin sulphate copolymers

Cyclic dithiobis(thioformates) derived from vicinal trans-diols decomposed upon pyrolysis or upon treatment with methyl sulfoxide containing catalytic amounts of base to give O,S-dithiocarbonates with accompanying inversion at the site of thiolation. With derivatives of vicinal cis-diols, fragmentation led only to thionocarbonates and the parent diols. Cyclic dithiobis(thioformates) of methyl 4,6-O-benzylidene-α-D-glucopyranoside, 1,2:5,6-di-O-isopropylidene-D-mannitol, and trans-1,2-cyclohexanediol decomposed to O,S-dithiocarbonates; whereas the dithiobis-(thioformates) of methyl 4,6-O-benzylidene-α-D-mannopyranoside and cis-1,2-cyclo-hexanediol decomposed only to thionocarbonates and the corresponding diols. The structures of the O,S-dithiocarbonates were confirmed by physical and chemical data.     

Membrane mobility agent alters the consequences of lectin-cell interaction in a malignant cell membrane

The membrane mobility agent 2-(2-methoxyethoxy)-ethyl 8-(cis-2-n-octylcyclopropyl)-octanoate promotes cap formation from wheat germ agglutinin-receptor combinations at the expense of agglutination in membranes of malignant mastocytoma cells.     

Resonance Raman and crystallographic studies on the complex [Fe2(bbpnol)2]·2DMF (bbpnol=N,N′-bis(2-hydroxybenzyl)-2-ol-1,3-propanediamine)

The ligand N,N′-bis(2-hydroxybenzyl)-2-ol-1,3-propanediamine (H₃bbpnol) reacts with iron(III) perchlorate forming two dinuclear bis-μ-alkoxo complexes, a ‘cis-trans’ isomer (complex 1) previously reported and a ‘cis-cis’ isomer (complex 2) characterized in this work. The main differences found in complex 2 structure are, (a) the four phenolic oxygens are trans to the alkoxo bridges; (b) each ligand is shared by the two Fe(III) ions occupying two coordination positions at each center. The Fe(III) centers in the resulting centrosymmetric structure in complex 2 have a distorted-octahedral geometry with the equatorial plane occupied by the phenolic and alcoholic oxygen atoms and the apical positions are filled by the aminic nitrogen atoms. The resonance Raman (RR) spectra of these two isomeric complexes are somewhat different with the intensity of some low-frequency modes increasing in the less symmetric core. The electronic spectra of both complexes are similar, but the molar absorptivities are substantially increased in complex 2, indicating the presence of an electronic coupling between the phenolate moieties trans in relation to the alkoxo bridge, and that phenolates coordinated cis to the alkoxo bridge do not seem to contribute to LMCT oscillator strength. This is directly reflected in the Raman excitation profiles (REP) of the chromophore modes, with the vibrational modes of the ‘cis-cis’ isomer showing a greater intensification compared with the ‘cis-trans’ isomer.     

Inhibitors of sterol biosynthesis. Syntheses of 14α-alkyl substituted 15-oxygenated sterols

The chemical syntheses of a number of 14α-alkyl substituted 15-oxygenated sterols have been pursued to permit evaluation of their activity in the inhibition of the biosynthesis of cholesterol and other biological effects. Described herein are the first chemical syntheses of 14α-ethyl-5α-cholest-7-en-3β-ol-15-one, bis-3β,15α-acetoxy-14α-ethyl-5α-cholest-7-ene, 3β-acetoxy-14α-ethyl-5α-cholest-7-en-15β-ol, 14α-ethyl-5α-cholest-7-en-3β,15β-diol, 14α-ethyl-5α-cholest-7-en-3β,15α-diol, 3β-hexadecanoyloxy-14α-ethyl-5α-cholest-7-en-15α-ol, 3β-hexadecanoyloxy-14α-ethyl-5α-cholest-7-en-15β-ol, bis-3β,15α-hexadecanoyloxy-14α-ethyl-5α-cholest-7-ene, 3β-hexadecanoyloxy-14α-ethyl-5α-cholest-7-en-15-one, 3α-benzoyloxy-14α-ethyl-5α-cholest-7-en-15-one, 14α-ethyl-5α-cholest-7-en-3α-ol-15-one, 14α-ethyl-5α-cholest-7-en-15-on-3β-yl pyridinium sulfate, 14α-ethyl-5α-cholest-7-en-15-on-3β-yl potassium sulfate (monohydrate), 14α-ethyl-5α-cholest-7-en-15-on-3α-yl pyridinium sulfate, 14α-ethyl-5α-cholest-7-en-15-on-3α-yl potassium sulfate (monohydrate), 3β-ethoxy-14α-ethyl-5α-cholest-7-en-15-one, 3β-acetoxy-14α-n-propyl-5α-cholest-7-en-15-one, 14α-n-propyl-5α-cholest-7-en-3β-ol-15-one, bis-3β, 15α-acetoxy-14α-n-propyl-5α-cholest-7-ene, 3β-acetoxy-14α-n-propyl-5α-cholest-7-en-15β-ol, 14α-n-propyl-5α-cholest-7-en-3β, 15α-diol, 14α-n-propyl-5α-cholest-7-en-3β, 15β-diol, 14α-n-butyl-5α-cholest-7-en-3β-ol-15-one, 3β-acetoxy-14-α-n-butyl-5α-cholest-7-en-15-one, bis-3β,15α-acetoxy-14α-n-butyl-5α-cholest-7-ene, 3β-acetoxy-14α-n-butyl-5α-cholest-7-en-15β-ol, 14α-n-butyl-5β-cholest-7-en-3β, 15β-diol, and 14α-n-butyl-5α-cholest-7-en-3β, 15α-diol.     

Studies on the stereoselective synthesis of a protected α-d-Gal-(1→2)-d-Glc fragment

A novel 1,2-cis stereoselective synthesis of protected α-d-Gal-(1→2)-d-Glc fragments was developed. Methyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-α-d-galactopyranosyl-(1→2)-3-O-benzoyl-4,6-O-benzylidene-α-d-glucopyranoside (13), methyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-α-d-galactopyranosyl-(1→2)-3,4,6-tri-O-benzoyl-α-d-glucopyranoside (15), methyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-α-d-galactopyranosyl-(1→2)-3-O-benzoyl-4,6-O-benzylidene-β-d-glucopyranoside (17), and methyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-α-d-galactopyranosyl-(1→2)-3,4,6-tri-O-benzoyl-β-d-glucopyranoside (19) were favorably obtained by coupling a new donor, isopropyl 2-O-acetyl-3-O-allyl-4,6-O-benzylidene-1-thio-β-d-galactopyranoside (2), with acceptors, methyl 3-O-benzoyl-4,6-O-benzylidene-α-d-glucopyranoside (4), methyl 3,4,6-tri-O-benzoyl-α-d-glucopyranoside (5), methyl 3-O-benzoyl-4,6-O-benzylidene-β-d-glucopyranoside (8), and methyl 3,4,6-tri-O-benzoyl-β-d-glucopyranoside (12), respectively. By virtue of the concerted 1,2-cis α-directing action induced by the 3-O-allyl and 4,6-O-benzylidene groups in donor 2 with a C-2 acetyl group capable of neighboring-group participation, the couplings were achieved with a high degree of α selectivity. In particular, higher α/β stereoselective galactosylation (5.0:1.0) was noted in the case of the coupling of donor 2 with acceptor 12 having a β-CH₃ at C-1 and benzoyl groups at C-4 and C-6.     

Biflavanoid proguibourtinidin carboxylic acids and their biflavanoid homologues from Acacia luederitzii

[4,6]- and [4,8]-Proguibourtinidin carboxylic acids (3,7,4′-trihydroxyl functionality) of 2,3-trans-3,4-trans: 2,3-cis- and 2,3-trans-3,4-trans: 2,3-trans-configuration based on (?)-epicatechin or (+)-catechin as constituent units, and their associated biflavanoid homologues, predominate in the heartwood of Acacia luederitzii. They are accompanied by stereochemical and functional analogues and by their putative flavan-3,4-diol and flavan-3-ol precursors.     

Configurational assignments of C-nitromethyl-C-hydroxy branched-chain carbohydrate derivatives by use of a europium shift-reagent in 1 H-N.M.R. spectroscopy

Configurational assignments for the tertiary alcoholic centers of four branched-chain 3-C-nitromethylglycopyranosides, namely, methyl 2-benzamido-4,6-O-benzylidene-2-deoxy-3-C-nitromethyl-α-D-allopyranoside (1), benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-3-C-nitromethyl-α-D-glucopyranoside (4), benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-3-C-nitromethyl-α-D-allopyranoside (5), and methyl 4,6-O-benzylidene-3-C-nitromethyl-2-O-p-tolylsulfonyl-α-D-glucopyranoside (8), were made on the basis of the downfield chemical shifts of their identifiable protons per molar equivalent of added Eu(fod)₃, as compared with those of model compounds, of known configuration, having a close structural relationship. In some cases, the assignments were corroborated by the position of the acetyl resonances in the unshifted 60-MHz p.m.r. spectra of the corresponding O-acetyl derivatives.     

Synthesis of phenyl 2-acetamido-2-deoxy-3-O-α-l-fucopyranosyl-β-d-glucopyranoside and related compounds

The reaction of phenyl 2-acetamido-2-deoxy-4,6- O-(p-methoxybenzylidene)-β-d-glucopyranoside with 2,3,4-tri-O-benzyl-α-l-fucopyranosyl bromide under halide ion-catalyzed conditions proceeded readily, to give phenyl 2-acetamido-2-deoxy-4,6-O-(p-methoxybenzylidene)-3-O-(2,3,4-tri-O-benzyl-α-l-fucopyranosyl)-β-d-glucopyranoside (8). Mild treatment of 8 with acid, followed by hydrogenolysis, provided the disaccharide phenyl 2-acetamido-2-deoxy-3-O-α-l-fucopyranosyl-β-d-glucopyranoside. Starting from 6-(trifluoroacetamido)hexyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranoside, the synthesis of 6-(trifluoroacetamido)hexyl 2-acetamido-2-deoxy-3-O-β-l-fucopyranosyl-β-d-glucopyranoside has been accomplished by a similar reaction-sequence. On acetolysis, methyl 2-acetamido-2-deoxy-3-O-α-l-fucopyranosyl-α-d-glucopyranoside gave 2-methyl-[4,6-di-O-acetyl-1,2-dideoxy-3-O-(2,3,4-tri-O-acetyl-α-l-fucopyranosyl)-α-d-glucopyrano]-[2, 1-d]-2-oxazoline as the major product.     

Resonance Raman spectroscopy of chemically modified retinals: Assigning the carbon-methyl vibrations in the resonance Raman spectrum of rhodopsin

To assign the observed vibrationsl modes in the resonance Raman spectrum of the retinylidene chromophore of rhodopsin, we have studied chemically modified retinals. The series of analogs investigated are the n-butyl retinals substituted at C₉ and C₁₃. The results obtained for the 11-cis isomer have clearly assigned the CCH₃ vibrational frequencies observed in the spectrum of the retinylidene chromophore. The data show that the C₍₉₎CH₃ stretching vibration can be assigned to the vibrational mode observed in the 1017 cm^?1 region, and the vibration detected at 997 cm^?1 can be assigned to the C₍₁₃CH₃ vibration. The C₍₅₎CH₃ stretching mode does not contribute to the vibrations observed in this region. The splitting in the C_(n)CH₃ (n = 9, 13) vibration is characteristic of the 11-cis conformation. The results on the modified retinals do not support the hypothesis that the splitting arises from equilibrium mixtures of 11-cis, 12-s-cis and 11-cis, 12-s-trans in solution. Thus, this splitting cannot be used to determine whether the chromophore in rhodopsin is in a 12-s-cis or 12-s-trans conformation. However, our results demonstrate that there are other vibrational modes in the spectra which are sensitive to this conformational equilibrium and we use the presence of a strong ~ 1271 cm^?1 mode in bovine and squid rhodopsin spectra as an indication that the chromophore in these pigments is 11-cis, 12-s-trans.     

Biotransformation of Unsaturated Long-Chain Fatty Acids by Eubacterium lentum

Eubacterium lentum (33 strains) isomerized the 12-cis double bond of C₁₈ fatty acids with cis double bonds at C-9 and C-12 into an 11-trans double bond before reduction of the 9-cis double bond. The 14-cis double bond of homo-γ-linolenic acid was isomerized by 29 strains into a 13-trans double bond. The same strains isomerized the 14-cis double bond of arachidonic acid into a 13-trans double bond and then isomerized the 8-cis double bond into a 7-trans double bond; the 13-cis double bond of 10-cis, 13-cis-nonadecadienoic acid was isomerized into a 12-trans double bond. None of these isomerization products was further reduced. Studies with resting cells showed optimal isomerization velocity at a linoleic acid concentration of 37.5 μM; higher concentrations were inhibitory. The pH optimum for isomerization was 7.5 to 8.5. The isomerase was inhibited by the sulfhydryl reagents iodoacetamide, bromoacetate, and N-ethylmaleimide and by the chelators EDTA and 1,10-phenanthroline.     

The synthesis of 3-amino-3-deoxy-α-d-glucopyranosyl α-d-glucopyranoside (3-amino-3-deoxy-α,α-trehalose

The preparation of 2,3-di-O-benzoyl-4,6-O-benzylidene-α-d-glucopyranosyl-2-O-benzoyl-4,6-O-benzylidene-α-d-ribo-hexopyranosid-3-ulose (3) from 4,6:4′,6′-di-O-benzylidene-α,α-trehalose (1) via the 2,3,2′-tribenzoate 2 has been improved. Reduction of 3 with sodium borohydride gave 2-O-benzoyl-4,6-O-benzylidene-α-d-allopyranosyl 2,3-di-O-benzoyl-4,6-O-benzylidene-α-d-glucopyranoside (4), which was converted into the methanesulfonate 5 and trifluoromethanesulfonate 6. Displacement of the sulfonic ester group in 6 with lithium azide was very facile and afforded a high yield of 3-azido-2-O-benzoyl-4,6-O-benzylidene-3-deoxy-α-d-glucopyranosyl 2,3-di-O-benzoyl-4,6-O-benzylidene-α-d-glycopyranoside (7), whereas similar displacement in 5 proceeded sluggishly, giving a lower yield of 7 together with an unsaturated disaccharide (8). The azido sugar 7 was converted by conventional reactions into the analogous 2,3,2′-triacetate 9, the corresponding 2,3,2′-triol 10, and deprotected 3-azido-3-deoxy-α-d-glucopyranosyl α-d-glucopyranoside (11). Hydrogenation of 11 over Adams' catalyst furnished crystalline 3-amino-3-deoxy-α,α-trehalose hydrochloride (12), the overall yield from 3 being 35%.     

Synthesis of 8-(hydroxyalkyl)adenines

Treatment of methyl 4,6-O-benzylidene-2-O-p-tolylsulfonyl-α-D-ribo-hexopyranosid-3-ulose (1) with triethylamine-methanol at reflux temperature yields methyl 2,3-anhydro-4,6-O-benzylidene-3-methoxy-α-D-allopyranoside (2), a derivative (3) of 3-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one, and methyl 4,6-O-benzylidene-α-D-ribo-hexopyranosid-3-ulose dimethyl acetal (4). The reaction of methyl 4,6-O benzylidene-3-O-p-tolylsulfonyl-α-D-arabino-hexopyranosid-2-ulose (12) with triethylamine-methanol afforded methyl 4,6-O-benzylidene-α-D-ribo-hexopyranosid-2-ulose dimethyl acetal (19) and methyl 2,3-anhydro-4,6-O-benzylidene-2-methoxy-α-D-allopyranoside (20); from the reaction of the β-D anomer (13) of 12, methyl 4,6-O-benzylidene-β-D-ribo-hexopyranosid-2-ulose dimethyl acetal (21) was isolated. Syntheses of the α-keto toluene-p-sulfonates 12 and 13 are described. Mechanisms for the formation of the compounds isolated from the reactions with triethylamine-methanol are proposed.     

Binding affinities of CRBPI and CRBPII for 9-cis-retinoids

Background

Cellular retinol binding-protein I (CRBPI) and cellular retinol binding-protein II (CRBPII) serve as intracellular retinoid chaperones that bind retinol and retinal with high affinity and facilitate substrate delivery to select enzymes that catalyze retinoic acid (RA) and retinyl ester biosynthesis. Recently, 9-cis-RA has been identified in vivo in the pancreas, where it contributes to regulating glucose-stimulated insulin secretion. In vitro, 9-cis-RA activates RXR (retinoid × receptors), which serve as therapeutic targets for treating cancer and metabolic diseases. Binding affinities and structure–function relationships have been well characterized for CRBPI and CRBPII with all-trans-retinoids, but not for 9-cis-retinoids. This study extended current knowledge by establishing binding affinities for CRBPI and CRBPII with 9-cis-retinoids.

Methods

We have determined apparent dissociation constants, K′_d, through monitoring binding of 9-cis-retinol, 9-cis-retinal, and 9-cis-RA with CRBPI and CRBPII by fluorescence spectroscopy, and analyzing the data with non-linear regression. We compared these data to the data we obtained for all-trans- and 13-cis-retinoids under identical conditions.

Results

CRBPI and CRBPII, respectively, bind 9-cis-retinol (K′_d, 11 nM and 68 nM) and 9-cis-retinal (K′_d, 8 nM and 5 nM) with high affinity. No significant 9-cis-RA binding was observed with CRBPI or CRBPII.

Conclusions

CRBPI and CRBPII bind 9-cis-retinol and 9-cis-retinal with high affinities, albeit with affinities somewhat lower than for all-trans-retinol and all-trans-retinal.

General significance

These data provide further insight into structure–binding relationships of cellular retinol binding-proteins and are consistent with a model of 9-cis-RA biosynthesis that involves chaperoned delivery of 9-cis-retinoids to enzymes that recognize retinoid binding-proteins.     

New syntheses of methyl 4,6-O-benzylidene-2-deoxy-3-C-methyl-α-d-arabino-hexopyranoside and its conversion into d-evermicose

Methyl 4,6-O-benzylidene-2-deoxy-3-C-methyl-α-d-arabino-hexopyranoside (4) was prepared from methyl 4,6-O-benzylidene-2,3-dideoxy-3-C-methylene-α-d-erythro-hexopyranoside (1b) and from methyl 4,6-O-benzylidetic-3 C-methyl-α-d-gluco-hexopyranoside (6a) by two different methods. Synthesis of d-evermicose3 (10 (2,6-dideoxy-3-C-methyl-d-arabino-hexose) was then achieved in four steps from 4.     

Synthèse de trithioorthocarbonates de pyranosides par thermolyse de bis(dithiocarbonates)

The thermal decomposition of methyl 4,6-O-benzylidene-2,3-di-O-[(methylthio)-thiocarbonyl]-α-d-glucopyranoside afforded methyl 4,6-O-benzylidene-2-thio-α-d-mannopyranoside 3-O,2-S-(S,S-dimethyl trithioorthocarbonate) and methyl 4,6-O-benzylidene-3-thio-α-d-allopyranoside 2-O,3-S-(S,S-dimethyl trithioorthocarbonate) in good yield. This decomposition can be generalized to 1,3-diols derived from sugars. Thus methyl 2,3-di-O-methyl-4,6-di-O-[(methylthio)thiocarbonyl]-α-d-glucopyranoside afforded in the same way the corresponding trithioorthocarbonates, following a regioselective process. The structures of these trithioorthocarbonates are confirmed by spectral and chemical proofs.     

Condensed tannins. Optically active diastereoisomers of (+)-mollisacacidin by epimerization

1. (+)-Mollisacacidin [(+)-3′,4′,7-trihydroxy-2,3-trans-flavan-3,4-trans- diol] is converted by autoclaving into the optically active free phenolic 2,3-trans-3-4-cis (12% yield), 2,3-cis-3,4-trans (11%) and 2,3-cis-3,4-cis (2·8%) diastereoisomers through epimerization at C-2 and C-4. 2. The relative configurations of the epimeric forms were determined by nuclear-magnetic-resonance spectrometry and paper ionophoresis in comparison with synthetic reference compounds, and was confirmed by chemical interconversions. 3. From this a scheme of epimerization is inferred and their absolute configurations are assigned as (2R:3S:4S), (2S:3S:4R) and (2S:3S:4S) respectively from the known absolute configuration (2R:3S:4R) of (+)-mollisacacidin.     

Reaktionen von kohlenhydraten mit dichlormethylendimethylammoniumchlorid: ein neuer weg zu 2-chlor-2-desoxy-, und 3-chlor-3-desoxyhexose-, und 3-chlor-3-desoxypentosederivaten

Treatment of methyl 4,6-O-benzylidene-α-D-mannopyranoside with dichloromethylenedimethylammonium chloride gave methyl 4,6-O-benzylidene-3-chloro-3-deoxy-2-(N,N-dimethylcarbamoyl)-α-D-altropyranoside and methyl 4,6-O-benzy]idene-2-chloro-2-deoxy-3-(N,N-dimethylcarbamoyl)-α-D-glucopyranoside. Methyl 4,6-O-benzylidene-α-D-allopyranoside gave under analogous conditions the corresponding 2-chloro-3-(N,N-dimethylcarbamoyl)-α-D-altrose and 3-chloro-2-(N,N-dimethylcarbamoyl)-α-D-glucose derivatives. Methyl 5-O-benzyl-α,β-D-ribofuranoside and methyl 5-O-methyl-β-D-ribofuranoside gave only the corresponding methyl 3-chloro-2-(N,N-dimethylcarbamoyl)-α-D-xylofuranoside derivatives.     

Screening of the genus Cercospora for secondary metabolites

Screening of 61 species of Cercospora grown on a potato-agar medium showed the presence of the phytotoxin cercosporin in 24 of them, and of dothistromin in 8. Some strains of C. beticola produce a yellow phytotoxin (CBT). The new metabolites cercosporin esters, ligustrone A, B, C, taiwapyrone, 3-methoxy-2,5,7-trihydroxy-1,4-naphthaquinone, cis-4,6-dihydroxymellein and ( ? )-11-acetyldehydrocurvularin were isolated besides the known cynodontin, ( ? )-dehydrocurvularin, (+ )-mellein and cis-3S,4S-4-hydroxymellein.     

Biosynthesis of geraniol and nerol in cell-free extracts of Tanacetum vulgare

Cell-free extracts from leaves of Tanacetum vulgare synthesised geraniol and nerol (3,7-dimethylocta-trans-2-ene-1-ol and its cis isomer) in up to 11·9 and 2·4% total yields from IPP-[4-¹⁴C] and MVA-[2-¹⁴C] respectively. Optimum preparations were obtained from plant material just before the onset of flowering. The ratio of the monoterpenols varied 28-fold for different preparations under conditions where these products or their phosphate esters were not interconverted. Similar extracts incorporated α-terpineol-[¹⁴C] and terpinen-4-ol-[¹⁴C] (p-menth-1-en-8- and -4-ol respectively) in 0·05 to 2·2% yields into a compound tentatively identified as isothujone (trans-thujan-3-one), and preparations from flowerheads converted IPP-[4-¹⁴C] in 2·7% yield into geranyl and neryl β-d-glucosides. Inhibitors of IPP-isomerase had little effect on the incorporation of IPP into the monoterpenols in cell-free systems from which endogenous compounds of low molecular-weight had been removed. The inference that a pool of protein-bonded DMAPP or its biogenetic equivalent was present was supported by the demonstration that geraniol and nerol biosynthesised in the absence of the inhibitors were predominantly (65 to 100%) labelled in the moiety derived from IPP.