Stereospecific Reduction of Ethyl 2′ -Ketopantothenate to Ethyl D-(+)-Pantothenate with Microbial Cells as a Catalyst

A novel enzymatic process for the synthesis of D-(+)-pantothenic acid through the asymmetric reduction of the 2′ -ketopantothenate ester is described. Candida macedoniensis AKU 4588 was found to convert ethyl 2′ -ketopantothenate (80 mg/ml) almost specifically to ethyl D-(+)-pantothenate (>98% enantiomeric excess), with a molar yield of 97.2%.     

Glycosidase-catalyzed deoxy oligosaccharide synthesis. Practical synthesis of monodeoxy analogs of ethyl beta-thioisomaltoside using Aspergillus niger alpha-glucosidase

Enzymatic transglycosylation using four possible monodeoxy analogs of p-nitrophenyl alpha-D-glucopyranoside (Glc alpha-O-pNP), modified at the C-2, C-3, C-4, and C-6 positions (2D-, 3D-, 4D-, and 6D-Glc alpha-O-pNP, respectively), as glycosyl donors and six equivalents of ethyl beta-D-thioglucopyranoside (Glc beta-S-Et) as a glycosyl acceptor, to yield the monodeoxy derivatives of glucooligosaccharides were done. The reaction was catalyzed using purified Aspergillus niger alpha-glucosidase in a mixture of 50 mM sodium acetate buffer (pH 4.0)/CH3CN (1:1 v/v) at 37 degrees C. High activity of the enzyme was observed in the reaction between 2D-Glc alpha-O-pNP and Glc beta-S-Et to afford the monodeoxy analogs of ethyl beta-thiomaltoside and ethyl beta-thioisomaltoside that contain a 2-deoxy alpha-D-glucopyranose moiety at their glycon portions, namely ethyl 2-deoxy-alpha-D-arabino-hexopyranosyl-(1,4)-beta-D-thioglucopyranoside and ethyl 2-deoxy-alpha-D-arabino-hexopyranosyl-(1,6)-beta-D-thioglucopyranoside, in 6.72% and 46.6% isolated yields (based on 2D-Glc alpha-O-pNP), respectively. Moreover, from 3D-Glc alpha-O-pNP and Glc beta-S-Et, the enzyme also catalyzed the synthesis of the 3-deoxy analog of ethyl beta-thioisomaltoside that was modified at the glycon alpha-D-glucopyranose moiety, namely ethyl 3-deoxy-alpha-D-ribo-hexopyranosyl-(1,6)-beta-D-thioglucopyranoside, in 23.0% isolated yield (based on 3D-Glc alpha-O-pNP). Products were not obtained from the enzymatic reactions between 4D- or 6D-Glc alpha-O-pNP and Glc beta-S-Et.     

Chemical aminoacylation of transfer ribonucleic acid. The reaction of Escherichia coli tRNA with ethyl N-benzyloxycarbonylorthoglycinate.

The alpha-carbethoxypentadecyltrimethylammonium (Septonex) salt of tRNA (Ib) was condensed with ethyl N-benzyloxycarbonylorthoglycinate (II) in dimethylformamide in vacuo and in the presence of H3PO4 as catalyst. Pancreatic RNAase degradation and phenylalanine acceptor activity showed a 55--60% conversion to the 2',3'-cyclic orthoglycinate derivative of tRNA (IIIb). The orthoester grouping of IIIb was quantitatively hydrolyzed in 80% formic acid at 0 degrees C for 15 min to give 2'(3')-O-(N-benzyloxycarbonyl)glycyl tRNA (IVb). The latter was stripped at pH 8.8 to give tRNA whose behavior on DEAE cellulose column and gel electrophoresis was similar to that of starting tRNA. The phenylalanine acceptor activity amounted to almost 80% of the starting tRNA.     

Isolation and characterization of three new classes of transformation-deficient mutants of Streptococcus pneumoniae that are defective in DNA transport and genetic recombination

A bifunctional enzyme, L-(+)-tartrate dehydrogenase-D-(+)-malate dehydrogenase (decarboxylating) (EC 1.1.1.93 and EC 1.1.1. . . , respectively), was discovered in cells of Rhodopseudomonas sphaeroides Y, which accounts for the ability of this organism to grow on L-(+)-malate. The enzyme was purified 110-fold to homogeneity with a yield of 51%. During the course of purification, including ion-exchange chromatography and preparative gel electrophoresis, both enzyme activities appeared to be in association. The ratio of their activities remained almost constant [1:10, L-(+)-tartrate dehydrogenase/D-(+)-malate dehydrogenase (decarboxylating)] throughout all steps of purification. Analysis by polyacrylamide gel electrophoresis revealed the presence of a single protein band, the position of which was coincident with both L-(+)-tartrate dehydrogenase and D-(+)-malate dehydrogenase (decarboxylating) activities. The apparent molecular weight of the enzyme was determined to be 158,000 by gel filtration and 162,000 by ultracentrifugation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis yielded a single polypeptide chain with an estimated molecular weight of 38,500, indicating that the enzyme consisted of four subunits of identical size. The isoelectric point of the enzyme was between pH 5.0 and 5.2. The enzyme catalyzed the NAD-linked oxidation of L-(+)-tartrate as well as the oxidative decarboxylation of D-(+)-malate. For both reactions, the optimal pH was in a range from 8.4 to 9.0. The activation energy of the reaction (delta Ho) was 71.8 kJ/mol for L-(+)-tartrate and 54.6 kJ/mol for D-(+)-malate. NAD was required as a cosubstrate, and optimal activity depended on the presence of both Mn2+ and NH4+ ions. The reactions followed Michaelis-Menten kinetics, and the apparent Km values of the individual reactants were determined to be: L-(+)-tartrate, 2.3 X 10(-3) M; NAD, 2.8 X 10(-4) M; and Mn2+, 1.6 X 10(-5) M with respect to L-(+)-tartrate; and D-(+)-malate, 1.7 X 10(-4) M; NAD, 1.3 X 10(-4); and Mn2+, 1.6 X 10(-5) M with respect to D-(+)-malate. Of a variety of compounds tested, only meso-tartrate, oxaloacetate, and dihydroxyfumarate were effective inhibitors. meso-Tartrate and oxaloacetate caused competitive inhibition, whereas dihydroxyfumarate caused noncompetitive inhibition. The Ki values determined for the inhibitors were, in the above sequence, 1.0, 0.014, and 0.06 mM with respect to L-(+)-tartrate and 0.28, 0.012, and 0.027 mM with respect to D-(+)-malate.     

Blockade ofNMDA receptors differentially affectsD-1 andD-2 mediated turning behavior in the 6-hydroxydopamine model of Parkinson

Summary In rats with unilateral lesion of the nigrostriatal dopaminergic pathway, L-DOPA induces contralateral turning through activation of denervated D-1 and D-2 receptors. Blockade of N-methyl-D-aspartate (NMDA) receptors by the non-competitive antagonist (+)MK-801, potentiated the contralateral turning induced by L-DOPA as well as that induced by the D-1 agonist SKF 38393, while D-2 mediated turning was almost completely inhibited. Administration of the D-1 antagonist SCH 23390 blocked (+)MK-801-induced potentiation of L-DOPA contralateral turning, confirming the D-1 nature of the effects observed. Immunohistochemical studies on the early gene c-fos, which is known to be activated by stimulation of supersensitive D-1 receptors, revealed sparse c-fos positive nuclei in the lesioned CPu after SKF 38393, while after combined administration of (+)MK-801 and SKF 38393 dense labelling was obtained. Blockade of NMDA receptors, differentially affects D-1 and D-2 mediated turning behavior, suggesting that different neuronal pathways are involved in the mediation of D-1 and D-2 responses.     

Microbial reduction of ethyl acetoacetate using Sclerotium rolfsii

Summary A method for the quantitative enantioselective bioreduction of ethyl acetoacetate [1] to optically pure (+)-S-ethyl-3 hydroxybutyrate [II] usingSclerotium rolfsii mycelium is described. In a synthetic medium 1 g mycelium (dry weight) could convert 1 g of I to II within 2–3 days of fermentation (pH 5.8, 30°C). This is the first report demonstrating use ofS. rolfsii biomass for asymmetric reduction to get chiral building blocks.     

Effects of synthetic ergot derivatives on the two identifiable giant neurons, sensitive to dopamine, of Achatina fulica Ferussac

On the two dopamine (DA)-sensitive giant neurones, PON (periodically oscillating neuron, excited by DA) and TAN (tonically autoactive neuron, inhibited by DA), of an African giant snail (Achatina fulica Férussac), effects of synthetic ergot derivatives, including lisuride and pergolide, which are considered to be dopamine agonists, were examined. Of the substances examined, three of the ergot derivatives related to pergolide, D-8,9-didehydro-6-propylergoline-8-methanol (LY149174), D-6-methyl-8 beta-(2-(methylsulfinyl)ethyl)ergoline (LY116470) and D-2-chloro-6-methyl-8 beta-(2-(methylsulfinyl)ethyl)ergoline (LY127817), showed excitatory effects on PON, while pergolide (D-8 beta-( (methylthio)methyl)-6-propylergoline, LY127809) and lisuride (N-D-6-methyl-8-isoergolenyl-N',N'-diethylcarbamide) had no effect. On the other hand, only D-6-methyl-8 beta-(2-(methylsulfinyl)ethyl)ergoline (LY116470) had any excitatory effects on TAN.     

Structural and conformational studies on deoxyguanosyl-3',5'-deoxyadenosine monophosphate and its ethyl phosphotriester analogs--left-handed dimers

The mode of base-base stacking, the handedness and the sugar(dGpA)phosphate backbone conformation of deoxyguanosyl 3'-5' deoxyadenosine and its diastereomeric ethyl phosphotriester analogs were studied by 1H NMR, UV and CD spectroscopy. The results indicate the three dimers are left-handed, while the sugar phosphate backbone is comprised predominantly of C2-endo,gg(C4-C5) and g'g (C5-O) conformers. The two bases are extensively stacked and interact about 90 degrees along the dyad axes. The extent of base overlap in dGpA is slightly greater than in either ethyl phosphotriester analog. The absolute configurations of the two ethyl phosphotriester diastereoisomers of dGpA can be assigned by one-dimensional and two-dimensional 1H NMR nuclear Overhauser enhancement experiments.     

Purification of bovine striatal dopamine D-2 receptor by affinity chromatography

Bovine striatal dopamine D-2 receptor has been purified approximately 2000-fold by affinity chromatography. The receptor, solubilized with cholic acid and sodium chloride, was adsorbed on haloperidol-linked Sepharose CL-6B and eluted with spiroperidol. The adsorption of receptor to the affinity matrix was biospecific as preincubation of the solubilized preparation with D-2 receptor agonists or antagonists blocked retention of receptor. The process also displayed stereoselectivity with respect to (+)- and (-)-butaclamol. Nondopaminergic agents such as mianserin and propranolol failed to exhibit any effect on the adsorption process. Elution of the receptor was also biospecific, as dopaminergic drugs were most effective (spiroperidol greater than haloperidol greater than dopamine) in eluting the bound receptor; whereas other agents, e.g. propranolol, mianserin, and acetic acid, were only slightly effective. One-cycle affinity purification resulted in a recovery of 12% of the original membrane-bound dopamine D-2 receptor with a specific activity of 169,600 fmol/mg of protein as assayed with [3H]spiroperidol binding. The order of potency of D-2 agonists (N-propylnorapomorphine greater than NO434 greater than apomorphine greater than dopamine) and antagonists (spiroperidol greater than (+)-butaclamol greater than domperidone) with the purified preparation was found to be similar to that of the solubilized dopamine D-2 receptor.     

Dopamine D-1 Receptor and Cyclic AMP-Dependent Phosphorylation in Parkinson''s Disease

D-1 and D-2 receptor densities, evaluated respectively by [3H]SCH 23390 and [3H]spiperone binding, and DARPP-32 (dopamine and adenosine 3':5'-monophosphate-regulated phosphoprotein-32K) concentrations, were studied in the brains of control and parkinsonian subjects postmortem. D-2 receptor density was unchanged in the putamen of parkinsonian patients. D-1 receptor density was unchanged in the putamen and substantia nigra pars reticulata (SNR) of parkinsonian patients, but decreased by 28% in the substantia nigra pars compacta (SNC). DARPP-32, which is localized in the same structures as D-1 receptors of which it is thought to represent the intracellular messenger, decreased by 45% in the putamen, 66% in the SNR, and 79% in the SNC. The decrease in D-1 receptors in the SNC may be due to degeneration of pallidonigral GABAergic neurons, but some of the D-1 receptors may be on the nigrostriatal dopaminergic neurons themselves. The dissociation between the alteration of D-1 receptor densities and DARPP-32 concentrations in both the striatum and substantia nigra, which are of the same order in the two structures, may be an index of functional hypoactivity of D-1 neurotransmission.     

Characteristics and function of Alcaligenes sp. NBRC 14130 esterase catalysing the stereo‐selective hydrolysis of ethyl chrysanthemate

Aims: Alcaligenes sp. NBRC 14130 was found as a strain hydrolysing a mixture of (±)‐trans‐ and (±)‐cis ethyl chrysanthemates to (1R,3R)‐(+)‐trans‐chrysanthemic acid. The Alcaligenes cells also have hydrolytic activity for 6‐aminohexanoate‐cyclic dimer (6‐AHCD, 1,8‐diazacyclotetradecane‐2,9‐dione). The correlation of function on the enzyme from the Alcaligenes strain with hydrolysis activities for both ethyl chrysanthemate and 6‐AHCD was demonstrated. Methods and Results: The esterase was purified to homogeneity. The purified esterase hydrolysed 20 mmol l^?1 ester including the four stereoisomers to the corresponding (+)‐trans acid with a 37% molar conversion of ethyl (+)‐trans chrysanthemate. The esterase showed high hydrolytic activity for various short‐chain fatty acid esters, n‐hexane amide and 6‐AHCD. The amino acid sequence of the Alcaligenes esterase was identical to that of Arthrobacter 6‐AHCD hydrolase (EC 3.5.2.12) and similar to that of fatty acid amide hydrolase (EC 3.5.1.4) from Rattus norvegicus, having both serine and lysine residues of the catalytic site and the consensus motif Gly‐X‐Ser‐X‐Gly. Conclusion: The stereo‐selective hydrolytic activity was found in Alcaligenes sp. NBRC14130 by screening of ethyl chrysanthemate‐hydrolysing activity in micro‐organisms, and the purified esterase also acted on fatty acid esters and amides. Significance and Impact of the Study: This study has demonstrated that there are great differences in the enzymatic properties, amino acid sequence and catalytic motif of esterases in both Alcaligenes and Arthrobacter globiformis with excellent stereo‐selectivity for (+)‐trans‐ethyl chrysanthemate, but the amino acid sequence of Alcaligenes esterase is identical to that of Arthrobacter 6‐AHCD hydrolase.     

The formation of dipeptides from amino acids and the 2'(3')-glycyl ester of an adenylate.

The yields of dipeptide obtained from the reaction of 0.2M 2'(3')-O-(glycyl)-adenosine-5'-(O-methylphosphate) and 0.2M amino acid at pH 8.2 ranged from 0.1% to 35.5% for a group of 15 amino acids. The yields of glyser (35.3%), gly-cys (11.8%) and gly-thr (5.4%) were considerably greater than dipeptide yields obtained from any of the other 12 amino acids (less than or equal to 1.7%). Aminolysis of 0.05M 2'(3')-O-(glycyl)-adenosine-5-'-(O-methylphosphate) by 0.4M serine ethyl ester yielded 53% glycylserine diketopiperazine, via N-(glycyl)-serine ethyl ester as a transient intermediate. The prebiotic significance of these reactions is discussed.     

Resolution and adrenergic activities of the optical isomers of 4-[1-(1-naphthyl)ethyl]-1H-imidazole.

Recently we synthesized a naphthalene analog of medetomidine, 4-[1-(1-naphthyl)ethyl]-1H-imidazole hydrochloride (1), and found it to be highly potent in adrenergic systems. The separation of optical isomers of this naphthalene analog was achieved by using the isomers of tartaric acid. The optical purities of the isomers were determined by HPLC using a chiral column. Using X-ray analysis the (+)-isomer was determined to have the S absolute configuration. It has been reported that the (+)-isomer of medetomidine (2) is the most potent enantiomer on alpha 2-adrenergic receptors. There were both qualitative and quantitative differences in biological activities of the optical isomers of 1 in alpha 1- and alpha 2-adrenergic receptor systems of guinea pig ileum and human platelets. (+)-(S)-1, but not (-)-(R)-1 was a selective agonist of alpha 2-mediated responses in ileum whereas (-)-(R)-1 was more potent than (+)-(S)-1 as an inhibitor of alpha 2-mediated platelet aggregation.     

Relative configuration of thioridazine enantiomers

The relative configuration of the enantiomers of thioridazine was defined to explore the stereochemistry associated with the selective binding of (?)-thioridazine to dopamine D-1 receptors and (+)-thioridazine to D-2 receptors. Using a seven-step stereoconservative synthesis, (?)-(S)-2-piperidinecarboxylic acid was converted to (?)-(S*)-2-(2-chloroethyl)-1-methylpiperidine, a literature (?)-thioridazine synthetic precursor. Accordingly, (?)- and (+)-thioridazine are the (S)- and (R)-enantiomers, respectively.     

Synthesis of novel 8-substituted carbocyclic analogs of 2',3'-dideoxyadenosine with activity against hepatitis B virus

Synthesis and antiviral activity of several new 8-substituted carbocyclic analogs of D-2',3'-dideoxyadenosine are described. The new 8-substituted analogs were synthesized via lithiation of carbocyclic 2',3'-dideoxyadenosine followed by quenching with electrophiles. This methodology allows for a divergent synthesis of a variety of 8-substituted analogs from carbocyclic 2',3'-dideoxyadenosine in high yields. 8-Methyl and 8-halogenated carbocyclic 2',3'-dideoxyadenosine analogs showed 6-25 fold more activity against hepatitis B virus than the unsubstituted carbocyclic D-2',3'-dideoxyadenosine.     

Two-dimensional NMR spectroscopy and structures of six lipid A species from Rhizobium etli CE3. Detection of an acyloxyacyl residue in each component and origin of the aminogluconate moiety

The chemical structures of six lipid A species (A, B, C, D-1, D-2, and E) purified from Rhizobium etli CE3 were investigated by one- and two-dimensional NMR spectroscopy. The R. etli lipid A subtypes each contain an unusual acyloxyacyl residue at position 2' as part of a conserved distal glucosamine moiety but differ in their proximal units. All R. etli lipid A species lack phosphate groups. However, they are derivatized with an alpha-linked galacturonic acid group at position 4', as shown by nuclear Overhauser effect spectroscopy. Component B, which had been not been reported in previous studies, features a beta, 1'-6 linked disaccharide of glucosamine acylated at positions 2, 3, 2', and 3' in a pattern that is typical of lipid A found in other Gram-negative bacteria. D-1 contains an acylated aminogluconate unit in place of the proximal glucosamine residue of B. C and E lack ester-linked beta-hydroxyacyl chains at position 3, as judged by their H-3 chemical shifts, and may be synthesized from B and D-1, respectively, by the R. etli 3-O-deacylase. D-2 is an isomer of D-1 that forms nonenzymatically by acyl chain migration. A may be an elimination product derived from D-1 during hydrolysis at 100 degrees C (pH 4.5), a step needed to release lipid A from lipopolysaccharide. Based on these findings, we propose a biosynthetic scheme for R. etli lipid A in which B is generated first by a variation of the E. coli pathway. The aminogluconate unit of D-1 could then be made from B by enzymatic oxidation of the proximal glucosamine. As predicted by our hypothesis, enzyme(s) can be demonstrated in extracts of R. etli that convert (14)C-labeled B to D-1.     

Biosynthesis of ethyl caproate and other short ethyl esters catalyzed by cutinase in organic solvent

The main objective of this work was to study the enzymatic synthesis of short chain ethyl esters, a group of relevant aroma molecules, by Fusarium solani pisi cutinase in an organic solvent media (iso-octane), and to assess the influence of different parameters on the reaction yield.Cutinase displayed high initial esterification rates in iso-octane, which amounted to 1.15 μmol min⁻¹ mg⁻¹ for ethyl butyrate (C₄ acid chain) and 1.06 μmol min⁻¹ mg⁻¹ for ethyl valerate (C₅ acid chain). High product yields, 84% for ethyl butyrate and 96% for ethyl valerate, were observed after 6 h of reaction, for an initial equimolar concentration of substrates (0.1 M).The highest product yield (97%) was observed for ethyl caproate (C₆) synthesis, a compound which is a part of natural apple and pineapple flavour, for an alcohol:acid molar ratio of 2 (0.2 M ethanol concentration).Cutinase affinity for short chain length carboxylic acids (C₄–C₆) in ester synthesis in iso-octane confirmed previous observations in reversed micellar system.     

Preparation and characterization of oligonucleotides containing S-[2-(N7-guanyl)ethyl]glutathione.

S-[2-(N7-Guanyl)ethyl]glutathione is the major adduct derived from modification of DNA with 1,2-dibromoethane in biological systems and is postulated to be a mutagenic lesion [Humphreys, W. G., Kim, D.-H., Cmarik, J. L., Shimada, T., & Guengerich, F. P. (1990) Biochemistry 29, 10342-10350]. Oligonucleotides containing this modified base were prepared by treatment of oligonucleotides with S-(2-chloroethyl)glutathione and purified by chromatography. The self-complementary oligonucleotide d(ATGCAT), when thus modified at the single guanine, appeared to associate with itself as judged by UV measurements, but CD and NMR measurements indicated a lack of hybridization, with a decrease in the melting temperature of greater than 10 degrees C. The same lack of self-association was noted when d(ATGCAT) was modified to contain an N-acetyl-S-[2-(N7-guanyl)ethyl]cysteine methyl ester moiety. The oligomer d-(C1A2T3G4C5C6T7) was modified to contain a single S-[2-(N7-guanyl)ethyl]glutathione moiety at the central position, and UV, CD, and 1H NMR studies indicated that this oligomer hybridized to its normal complement d(A8G9G10C11A12T13G14), although the binding was considerably weakened by adduction (imino proton NMR spectroscopy in the presence of H2O indicated that the hydrogen bond signals seen in the oligomer were all broadened upon modification). All proton resonances were identified using two-dimensional 1H NMR spectroscopy. Adduct formation affected the chemical shifts of the base and 1', 2', and 2" protons of T3 and C5, the 2" proton of C6, and the 8 and 1' protons of C11, while little effect was observed on other protons. No cross-peaks were detected between the glutathione and oligomer moieties in two-dimensional nuclear Overhauser enhanced NMR studies. These results suggest that a rather local structural perturbation occurs in the DNA oligomer upon modification and that the glutathione moiety appears to be relatively unperturbed by its placement in the duplex. When the cytosine in the normal d(AGGCATG) complement to d-(CATGCCT) was changed to each of the other three potential bases at the central position, no hybridization with the oligomer d(CATGCCT) containing S-[2-(N7-guanyl)ethyl]glutathione was detected. We conclude that these N7-guanyl derivatives destabilize hybridization and that bases other than cytosine do not appear to show preferential thermodynamic bonding to these adducts, at least in the sequences examined to date.(ABSTRACT TRUNCATED AT 400 WORDS)     

The metabolism of 2-chloro-1-(2′,4′-dichlorophenyl)vinyl diethyl phosphate (Chlorfenvinphos) in the dog and rat

1. A single oral dose of [(14)C]Chlorfenvinphos to rats is quantitatively eliminated in 4 days. Rats do not show a sex difference in the elimination pattern and show only a small degree of biological variation in the total excretion data. Of the label 87.2% is excreted in the urine (67.5% in the first day after dosage), 11.2% in the faeces and 1.4% in the expired gases; less than 0.9% of (14)C is present in the gut and contents after 4 days. 2. After oral administration of [(14)C]Chlorfenvinphos to dogs, 94.0% (91.8-97.6%) of the (14)C is excreted in the urine and faeces during 4 days. Dogs do not show a sex difference in the pattern of elimination, and excretion of radioactivity in the urine is very rapid: 86.0% of (14)C during 0-24hr. 3. Chlorfenvinphos is completely metabolized in rats and dogs: unchanged Chlorfenvinphos is absent from the urine and from the carcass, when elimination is complete. In rats, 2-chloro-1-(2',4'-dichlorophenyl)vinyl ethyl hydrogen phosphate accounts for 32.3% of a dose of Chlorfenvinphos, [1-(2',4'-dichlorophenyl)ethyl beta-d-glucopyranosid]uronic acid for 41.0%, 2,4-dichloromandelic acid for 7.0%, 2,4-dichlorophenylethanediol glucuronide for 2.6% and 2,4-dichlorohippuric acid for 4.3%; in dogs, 2-chloro-1-(2',4'-dichlorophenyl)vinyl ethyl hydrogen phosphate accounts for 69.6%, [1-(2',4'-dichlorophenyl)ethyl beta-d-glucopyranosid] uronic acid for 3.6%, 2,4-dichloromandelic acid for 13.4% and 2,4-dichlorophenylethanediol glucuronide for 2.7%. 4. Dogs and rats show a species difference in the rate of excretion of (14)C in the urine, and in the proportions of the metabolites, with the exception of 2,4-dichlorophenylethanediol glucuronide, that are excreted in the urine. Alternative explanations for the latter species difference are suggested. 5. 2-Chloro-1-(2',4'-dichlorophenyl)vinyl ethyl hydrogen phosphate and 2,4-dichlorophenacyl chloride probably lie on the main metabolic pathway of Chlorfenvinphos, since, in common with that insecticide, they give rise to [1-(2',4'-dichlorophenyl)ethyl beta-d-glucopyranosid]uronic acid and 2,4-dichloromandelic acid as major metabolites in the urine. 6. The proposed scheme for the metabolism of Chlorfenvinphos represents a detoxication mechanism.     

Dihydroflavonols from Lannea coromandelica

The dihydroflavonols, (2R,3S)-(+)-3',5-dihydroxy-4',7-dimethoxydihydroflavonol and (2R,3R)-(+)-4',5,7-trimethoxydihydroflavonol were isolated from the stem bark of Lannea coromandelica, along with the known (2R,3R)-(+)-4',7-di-O-methyldihydroquercetin, (2R,3R)-(+)-4',7-di-O-methyldihydrokaempferol and (2R,3R)-(+)-4'-O-methyldihydroquercetin. All five compounds were isolated for the first time from the genus Lannea; furthermore, (2R,3S)-(+)-3',5-dihydroxy-4',7-dimethoxydihydroflavonol, was a rare cis-type isomer. The structures of all compounds were elucidated by spectroscopic methods including 2D NMR and CD analysis.