Synthesis of dl-4,5,6-trinor-3,7-inter-m-phenylene-3-oxaprostaglandins including one which inhibits platelet aggregation

The synthesis of dl-4,5,6-trinor-3,7-inter-m-phenylene-3-oxaprostaglandins of the E₁ and F₁ series^** from 6-endo-(1-heptenyl)-bicyclo[3:1:0]hexan-3-one (III), is described. Preliminary biological screening data for gerbil colon smooth muscle stimulation, rat blood pressure and substrate specificity toward 15-hydroxyprostaglandin dehydrogenase is presented. Platelet function studies, both in vitro and in vivo of dl-4,5,6-trinor-3,7-inter-m-phenylene-3-oxa-PGE₁, methyl ester (VIII) are presented.     

Synthesis of d1-4,5,6-trinor-3,7-inter-m-phenylene-3-oxaprostaglandins including one which inhibits platelet aggregation

The synthesis of $\text{d1}$-4,5,6-trinor-3,7-inter-$\text{m}$-phenylene-3-oxaprostaglandins oxaprostaglandins of the E₁ and F₁α series⁷ from 6-endo-(1-heptenyl)-bicyclo[3:1:0]hexan-3-one (III), is described. Preliminary biological screening data for gerbil colon smooth muscle stimulation, rat blood pressure and substrate specificity toward 15-hydroxyprostaglandin dehydrogenase is presented. Platelet function studies, both $\text{in vitro}$ and $\text{in vivo}$ of $\text{d1}$-4,5,6-trinor-3,7-inter-$\text{m}$-phenylene-3-oxa-PGE₁, methyl ester (VIII) are presented.     

Hydrolysis of an orally active platelet inhibitory prostanoid amide in the plasma of several species

The prostanoid 3-oxa-4,5,6-trinor-3,7-inter-m-phenylene-PGE1-amide (OI-PGE1-amide) has a prolonged duration of oral platelet aggregation inhibitory activity when compared to the parent free acid (OI-PGE1) in the rat. When incubated in rat plasma at 1 microgram/ml for 30 seconds prior to addition of ADP, OI-PGE1-amide inhibits in vitro rat platelet aggregation approximately 50%. OI-PGE1 inhibits at 1 ng/ml. Inhibition of platelet aggregation by plasma incubated with OI-PGE1-amide (1 microgram/ml) increases with time and the rate of this increase differs with species. Incubation of OI-PGE1 in plasma does not result in an increase of platelet inhibitory activity with time. The increase of platelet inhibitory activity was assumed to indicate hydrolysis of OI-PGE1-amide to the more active OI-PGE1. A compound, different from OI-PGE1-amide, was isolated by an ion exchange/silica gel separation sequence from an incubation of OI-PGE1-amide in rat plasma. It had potent platelet aggregation inhibitory activity. This material was shown to be OI-PGE1 by thin-layer chromatography, gas chromatography and mass spectral analysis. Studies with [3H]-OI-PGE1-amide confirmed the formation of OI-PGE1 in plasma incubations. Amide hydrolytic activity was significantly different between species, the rank order being: rat greater than guine pig greater than monkey = human greater than dog. This relationship corresponded with that determined by measuring the increase in platelet inhibitory activity with time in plasma incubations of OI-PGE1-amide reported above. Present data indicate that (a) OI-PGE1-amide is hydrolyzed to the parent acid by plasma enzymes of several species and (b) hydrolytic activity of plasma varies widely between species.     

Duration of activity of the acid, methyl ester and amide of an orally active platelet aggregation inhibitory prostanoid in the rat

The prostanoid 3-oxa-4,5,6-trinor-3,7-inter- -phenylene PGE₁ (OI-PGE₁) has been shown to be a more potent inhibitor of ADP-induced human platelet aggregation than PGE₁. OI-PGE₁ inhibits ex vivo ADP-induced platelet aggregation for 60 minutes after an oral dose of 20 mg/kg to rats. Present studies compare duration of ex vivo inhibition to ADP-induced platelet aggregation in the rat by OI-PGE₁, its methyl ester and amide after administration by various routes. All oral (p.o.) and intraduodenal (i.d.) doses were 20 mg/kg and all intravenous (i.v.) doses were 1 mg/kg. OI-PGE₁ and its methyl ester had the same duration of activity after i.v. (60 min.) and p.o. (60 min.) administration, however, the methyl ester, when administered i.d., had a longer duration of activity than the free acid i.d. (>90 min. vs. 60 min.). OI-PGE₁-amide had significantly longer duration than the acid or methyl ester after i.v. (>120 min.), p.o. (>240 min.) or i.d. (>240 min.) administration. Present data suggest that in the rat (1) intestinal absorption of OI-PGE₁-methyl ester is more efficient than it is for the free acid and (2) due to metabolic and/or distributional differences between OI-PGE₁ and its amide, the amide has a much greater duration of activity.     

Hydrolysis of an orally active platelet inhibitory prostanoid amide in the plasma of several species

The prostanoid 3-oxa-4,5,6-trinor-3,7-inter-m-phenylene-PPGE₁-amide (OI-PGE₁-amide) has a prolonged duration of oral platelet aggregation inhibitory activity when compared to the parent free acid (OI-PGE₁) in the rat. When incubated in rat plasma at 1μg/ml for 30 seconds prior to addition of ADP, OI-PGE₁-amide inhibits in vitro rat platelet aggregation ≈50%. OI-PGE₁ inhibits at 1 ng/ml. Inhibition of platelet aggregation by plasma incubated with OI-PGE₁-amide (1μg/ml) increases with time and the rate of this increase differs with species. Incubation of OI-PGE₁ in plasma does not result in an increase of platelet inhibitory activity with time. The increase of platelet inhibitory activity was assumed to indicate hydrolysis of OI-PGE₁-amide to the more active OI-PGE₁. A compound, different from OI-PGE₁-amide, was isolated by an ion exchange/silica gel separation sequence from an incubation of OI-PGE₁-amide in rat plasma. It had potent platelet aggregation inhibitory activity. This material was shown to be OI-PGE₁ by thin-layer chromatography, gas chromatography and mass spectral analysis. Studies with [³H]-OI-PGE₁-amide confirmed the formation of OI-PGE₁ in plasma incubations. Amide hydrolytic activity was significantly different between species, the rank order being: rat > guinea pig > monkey human > dog. This relationship corresponded with that determined by measuring the increase in platelet inhibitory activity with time in plasma incubations of OI-PGE₁-amide reported above. Present data indicate that (a) OI-PGE₁-amide is hydrolyzed to the parent acid by plasma enzymes of several species and (b) hydrolytic activity of plasma varies widely between species.     

Novel metabolism of 1 alpha,25-dihydroxyvitamin D3 with C24-C25 bond cleavage catalyzed by human CYP24A1

Our previous study revealed that human CYP24A1 catalyzes a remarkable metabolism consisting of both C-23 and C-24 hydroxylation pathways that used both 25(OH)D(3) and 1alpha,25(OH)(2)D(3) as substrates, while rat CYP24A1 showed extreme predominance of the C-24 over C-23 hydroxylation pathway [Sakaki, T., Sawada, N., Komai, K., Shiozawa, S., Yamada, S., Yamamoto, K., Ohyama, Y. and Inouye, K. (2000) Eur. J. Biochem. 267, 6158-6165]. In this study, by using the Escherichia coli expression system for human CYP24A1, we identified 25,26,27-trinor-23-ene-D(3) and 25,26,27-trinor-23-ene-1alpha(OH)D(3) as novel metabolites of 25(OH)D(3) and 1alpha,25(OH)(2)D(3), respectively. These metabolites appear to be closely related to the C-23 hydroxylation pathway, because human CYP24A1 produces much more of these metabolites than does rat CYP24A1. We propose that the C(24)-C(25) bond cleavage occurs by a unique reaction mechanism including radical rearrangement. Namely, after hydrogen abstraction of the C-23 position of 1alpha,25(OH)(2)D(3), part of the substrate-radical intermediate is converted into 25,26,27-trinor-23-ene-1alpha(OH)D(3), while a major part of them is converted into 1alpha,23,25(OH)(3)D(3). Because the C(24)-C(25) bond cleavage abolishes the binding affinity of 1alpha,25(OH)D(3) for the vitamin D receptor, this reaction is quite effective for inactivation of 1alpha,25(OH)D(3).     

Nucleotide sequence analysis of two simian virus 40 mutants with deletions in the late region of the genome.

Two mutants of simian virus 40, dl-1261 and dl-1262, have deletions that map between coordinated 0.90 and 0.95 (Cole et al., J. Virol 24:277--294, 1977). Both affect the structure of the two minor proteins VP2 and VP3. The precise location and size of the deletions have now been determined by nucleotide sequence analysis. Mutant dl-1261 is deleted of 54 base pairs, is temperature sensitive for the protein defined by the D complementation group, and promotes the synthesis of shorter VP2 and VP3 polypeptides. Mutant dl-1262 is viable irrespective of temperature and has a deletion of 36 base pairs, 23 of which overlap the deletion in dl-1261. Since these mutants produce normal VP1, the deleted regions probably have no function in the splicing of precursor RNA to the VP1 mRNA.     

Synthesis of adiposin-1 and related compounds

The synthesis is described of adiposin-1 (2a), isolated from an α-d-glucosidase inhibitor complex, adiposin, produced by Streptomyces caluvs TM-521. The synthesis involved the coupling of 1,6-anhydro-4-O-(3,4-anhydro-α-d-galactopyranosyl)-β-d-glucopyranose (13) with the di-O-isopropylidene derivative (7) of dl-(1,4,$\text{6}\text{5}$)-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexenylamine. All possible diastereoisomers of the secondary amine were isolated by chromatography on silica gel. Their structures were tentatively assigned on the basis of ¹H-n.m.r. spectroscopy and optical rotation. Likewise, both the core-structure (4) of adiposin and the saturated analog (22) of 2a were synthesized.     

A study on the tricarboxylic acid cycle and the synthesis of acetylcholine in the lobster nerve

1. The biosynthetic origin of the amide substituent of N-(alpha-hydroxyethyl)lysergamide has been studied. 2. [1-(14)C]Acetate, [(14)C]formate, [2-(14)C]mevalonic acid lactone, [2-(14)C]indole, dl-[3-(14)C]tryptophan, dl-[3-(14)C]serine, dl-[2-(14)C]alanine and [2-(14)C]pyruvate were efficiently incorporated into the alkaloid, but not dl-[1-(14)C]alanine or [1-(14)C]pyruvate. 3. Only the dl-[2-(14)C]alanine- and [2-(14)C]pyruvate-derived alkaloid contained appreciable radioactivity in the amide substituent. 4. l-[(15)N]Alanine-derived alkaloid was shown to be specifically labelled in the amide nitrogen. However, l-[(14)C,(15)N]alanine was found to be incorporated into the methylcarbinolamide substituent with an appreciable increase in the (15)N/(14)C ratio, suggesting that alanine is not the direct precursor of this moiety.     

An automated colorimetric method for the measurement of 3-hydroxybutyrate concentration

An automated colorimetric method is presented for analysis of dl-3-hydroxybutyrate concentration using the Technicon AutoAnalyzer. The method is capable of measuring dl-3-hydroxybutyrate concentration in hemolyzed “blood” or plasma, with greater sensitivity and less enzyme than a previous automated method applicable only to serum.     

Biosynthetis of phytoquinones. Biosynthetic origins of the nuclei and satellite methyl groups of plastoquinone, tocopherols and tocopherolquinones in maize shoots, bean shoots and ivy leaves

1. By using dl-[ring-(14)C]phenylalanine, dl-[beta-(14)C]phenylalanine, dl-[alpha-(14)C]-tyrosine and dl-[beta-(14)C]tyrosine it was shown that in maize shoots (Zea mays) the nucleus and one nuclear methyl group of each of the following compounds, plastoquinone, gamma-tocopherol (aromatic nucleus) and alpha-tocopherolquinone, are formed from the nuclear carbon atoms and beta-carbon atom respectively of either exogenous phenylalanine or exogenous tyrosine. With ubiquinone only the aromatic ring of the amino acid is used in the synthesis of the quinone nucleus. Chemical degradation of plastoquinone and gamma-tocopherol molecules labelled from l-[U-(14)C]tyrosine established that a C(6)-C(1) unit directly derived from the amino acid is involved in the synthesis of these compounds. Radioactivity from [beta-(14)C]cinnamic acid is not incorporated into plastoquinone, tocopherols or tocopherolquinones, demonstrating that the C(6)-C(1) unit is not formed from any of the C(6)-C(1) phenolic acids associated with the metabolism of this compound. 2. The incorporation of radioactivity from l-[U-(14)C]tyrosine, dl-[beta-(14)C]tyrosine and dl-[U-(14)C]phenylalanine into bean shoots (Phaseolus vulgaris) and dl-[beta-(14)C]tyrosine and l-[Me-(14)C]methionine into ivy leaves (Hedera helix) was also investigated. Similar results were obtained to those reported for maize, except that in beans phenylalanine is only used for ubiquinone biosynthesis. This is attributed to the absence of phenylalanine hydroxylase from these tissues. In ivy leaves it is found that the beta-carbon atom of tyrosine gives rise to the 8-methyl group of delta-tocopherol, and it is suggested that for all other compounds examined it will give rise to the nuclear methyl group meta to the polyprenyl unit. 3. Preliminary investigations with the alga Euglena gracilis showed that in this organism ring-opening of tyrosine occurs to such an extent that the incorporation data from radiochemical experiments are meaningless. 4. The above results, coupled with previous observations, are interpreted as showing that in higher plants the nucleus of ubiquinone can be formed from either phenylalanine or tyrosine by a pathway involving as intermediates p-coumaric acid and p-hydroxybenzoic acid. Plastoquinone, tocopherols and alpha-tocopherolquinone are formed from p-hydroxyphenylpyruvate by a pathway in which the aromatic ring and C-3 of the side chain give rise respectively to the nucleus and to one nuclear methyl group. 5. Dilution experiments provided evidence that in maize shoots p-hydroxyphenylpyruvic acid and homogentisic acid (produced from p-hydroxyphenylpyruvic acid) are involved in plastoquinone biosynthesis, and presumably the biosynthesis of related compounds: however, other possible intermediates in the conversion including toluquinol (the aglycone of the proposed key intermediate) showed no dilution effects. Further, radioactivity from [Me-(14)C]toluquinol is not incorporated into any of the compounds examined. 6. Dilution experiments with 3,4-dihydroxybenzaldehyde and radioactive-labelling experiments with 3,4-dihydroxy[U-(14)C]benzoic acid demonstrated that these compounds are not involved in the biosynthesis of either ubiquinone or phylloquinone in maize shoots. 7. Evidence is also presented to show that in maize shoots ring-opening of the aromatic amino acids takes place. The suggestion is offered that this may take place via homogentisic acid, as in animals and some micro-organisms.     

Sesquiterpenoids from Teucrium ramosissimum

An antiplasmodial bioguided investigation of the EtOAc extract of the aerial parts of Teucrium ramosissimum led to isolation and identification of three sesquiterpenoids, teucmosin, 4α-hydroxy-homalomenol C, 1β,4β,7α-trihydroxy-8,9-eudesmene and two trinorsesquiterpenoids, 4β-hydroxy-11,12,13-trinor-5-eudesmen-1,7-dione and 1β,4β-dihydroxy-11,12,13-trinor-8,9-eudesmen-7-one together with five known sesquiterpenoids, oplopanone, homalomenol C, oxo-T-cadinol, 1β,4β,6β-trihydroxyeudesmane, 1β,4β,7α-trihydroxyeudesmane and four flavonoids, 5-hydroxy-7,4′-dimethoxyflavone, salvigenin, genkwanin and cirsimaritin. The structures and the relative stereochemistry were elucidated by extensive spectroscopic studies including 1D and 2D NMR and mass spectrometry (MS). Homalomenol C, 4β-hydroxy-11,12,13-trinor-5-eudesmen-1,7-dione, oxo-T-cadinol and 1β,4β,6β-trihydroxyeudesmane displayed a significant in vitro antiplasmodial activity against Plasmodium falciparum with IC₅₀ values ranging from 1.2 to 5.0 μg/ml. Furthermore, no cytotoxicity was observed upon the human diploid lung cell line MRC-5 for these compounds.     

Microbial metabolism of amino ketones: l-1-Aminopropan-2-ol dehydrogenase and l-threonine dehydrogenase in Escherichia coli

1. A wide range of intermediary metabolites and substrate analogues have no effect on the oxidation of dl-1-aminopropan-2-ol to aminoacetone by washed-cell suspensions of Escherichia coli. Only dl-2-hydroxy-2-phenylethylamine, dl-1,3-diaminopropan-2-ol, dl-serine and l-1-(3,4-dihydroxyphenyl)-2-aminoethanol act as inhibitors. 2. Dialysed cell-free extracts of E. coli exhibit an NAD(+)-dependent dl-1-aminopropan-2-ol-dehydrogenase activity of approx. 8mmumoles of aminoacetone formed/mg. of protein/min. at the pH optimum of approx. 10. The K(m) values for the coenzyme and dl-amino alcohol are approx. 0.4 and 10.0mm respectively. A smaller peak of activity occurs at pH7.0-7.2, the K(m) for NAD(+) at pH7 being approx. 0.05mm. 3. Enzyme activity in cell-free extracts is inhibited by dl-2-hydroxy-2-phenylethylamine, dl-1-aminopropane-2,3-diol and dl-serine. dl-Phenylserine and dl-1-aminobutan-2-ol are oxidized to compounds reacting as amino ketones. 4. In fresh cell-free extracts l(+)-1-aminopropan-2-ol preparations are oxidized more rapidly than racemic or laevo-rotatory material, the d(-)-enantiomorph appearing to act as a competitive inhibitor. The K(m) for l(+)-1-aminopropan-2-ol appears to be approx. 1.5mm when highly resolved substrate preparations are used, either in the free base form or as the l(+)-tartrate salt. 5. l(+)-1-Aminopropan-2-ol dehydrogenase is a labile enzyme, and in appropriately treated extracts activity towards the d-enantiomorph is detectable and relatively higher than that towards the l-enantiomorph. 6. Optimum activity of l-threonine-dehydrogenase in cell-free extracts is exhibited at pH9.6 in the presence of NAD(+). The K(m) values for coenzyme and amino acid substrate are approx. 0.08 and 5.0mm respectively. This enzyme is distinct from 1-aminopropan-2-ol dehydrogenases on the basis of kinetic evidence, and the separation of activities by gel filtration. 7. Both l-threonine and dl-1-aminopropan-2-ol dehydrogenases are markedly inhibited by 8-hydroxyquinoline and p-chloromercuribenzoate, but only slightly by other chelating and thiol reagents. 8. E. coli is incapable of growth on simple synthetic media, containing a variety of carbon sources, when dl-1-aminopropan-2-ol is supplied as the sole source of nitrogen. It appears unlikely that the micro-organism can deaminate aminoacetone. 9. The metabolic roles of l-threonine dehydrogenase, aminoacetone and 1-aminopropan-2-ol dehydrogenases are discussed.     

Eudesmane-type sesquiterpenes from the liverwort Apomarsupella revolute

Phytochemical investigation of the Et₂O extract of liverwort Apomarsupella revolute led to isolation and identification of five new eudesmane-type sesquiterpenoids, 6β-hydroxy-9β-acetoxy-eudesma-4,11-dien (1), 6β-hydroxy-9β-acetoxy-eudesma-4,11-dien-3-one (2), 5α,6β-dihydroxy-9β-acetoxy-eudesma-4(15),11-dien (3) 4β-hydroxy-9β-acetoxy-11,12,13-trinor-5-eudesmen-7-one (4) and 4β-methox-9β-acetoxy-11,12,13-trinor-5-eudesmen-7-one (5), two of which were trinorsesquiterpenoids. Their structures were established unequivocally on the basis of spectroscopic data analysis. All compounds were preliminary bioscreened for their cytotoxicities and antifungal activities.     

Synthesis,Characterization, and Antifungal Activity of Some New Thieno[2,3-b]pyridines Incorporating Quinazoline or Benzimidazole Moiety

Russian Journal of Bioorganic Chemistry - Reaction of 4,6-dimethyl-3-cyanopyridine-2(1H)-thione (IIIa) or 4,5,6-trisubstituted-3-cyanopyridine-2(1H)-thiones (IIIb–d) with...     

A circular dichroism study of the binding of CC-1065 to B and Z form poly(dl-5BrdC).poly(dl-5BrdC)

CC-1065, Benzo[1,2-b:4,3-b']dipyrrole-3(2H)-carboxamide, 7-[[1,6-dihydro-4-hydroxy-5-methoxy-7-[(4,5,8,8a-tetrahydro-7-methyl-4- oxocyclopropa[c]pyrrolo[3,2-e]indol-2(1H)-yl)carbonyl]benzo [1,2-b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-1,6-dihydro-4-hydroxy- 5-methoxy-, (7bR,8aS), binds to the B form of poly(dl-5BrdC).poly(dl-5BrdC) to yield a reversibly bound species whose stability with respect to an irreversibly bound species (presumably the inosine N-3 adduct) is much greater than it is for other DNA polymers. Competitive binding experiments with netropsin, show that this reversibly bound species of CC-1065 contains CC-1065 in the minor groove of the double helix. A review of the CC-1065 binding data obtained on other synthetic DNA polymers suggests that the widely different rates of species conversion shown by these polymers may result from small differences in DNA secondary structure rather than from different alkylating abilities of the adenine or inosine N-3 active site. CC-1065 converts the Z-form of poly(dl-5BrdC).poly(dl-5BrdC) in 3.5 M sodium chloride to the B form and does not bind to the Z form in this solvent system. CC-1065 bound to the B form polymer inhibits the formation of the Z form if the helix is saturated with CC-1065. Regions of the polymer without bound CC-1065 can convert to the Z form with added salt, producing a situation where the polymer contains both the B and Z conformations. In 4.0 M sodium chloride, where the Z conformation is also predominate, the addition of CC-1065 causes chiral aggregates to form, and CC-1065 binds to the aggregates. The addition of dimethylformamide in the absence of CC-1065 or a simple dilution of the 4.0 M sodium chloride polymer solution with water also causes aggregation, indicating that the Z form of this polymer in 4.0 M sodium chloride is unstable with respect to an aggregated form.     

Hexahydrobenzofuranoid neolignans from an Aniba species

The trunk wood of an Amazonian Aniba species contains three novel neolignans: (2R, 3R, 3aS, 5R)-3a-allyl-5-methoxy-2-(3,4,5-trimethoxyphenyl)-3-methyl-2,3,3a,4,5,6-hexahydro-6-oxobenzofuran (canellin-D), (2R,3R,3aS,5R)-3a-allyl-5,7-dimethoxy-2-(3-methoxy-4,5-methylenedioxyphenyl)-3-methyl-2,3,3a,4,5,6-hexahydro-6-oxobenzofuran (canellin-E) and (2S,3S,3aS,5R)-3a-allyl-5-methoxy-2-(3-methoxy-4,5-methylenedioxyphenyl)-3-methyl-2,3,3a,4,5,6-hexahydro-6-oxobenzofuran (armenin-C). The absolute stereochemistries of these and of all other known hexahydro-6-oxobenzofurans were determined by CD comparisons with model compounds.     

Effects of some prostaglandin E1 analogues on guinea pig and human respiratory tract

The effects of (a) 4, 5, 6-trinor-3, 7-inter-m-phenylene PGE1 methyl ester, (b) 4, 5, 6 trinor-3, 7-inter-m-phenylene 3 oxa PGE1 and (c) 4, 5, 6 trinor-3, 7-inter-m-phenylene 3 oxa PGE1 methyl ester on human and guinea pig respiratory tract muscle in vitro and in vivo have been studied. All the analogues relaxed the isolated preparations of guinea-pig tracheal chain, human tracheal, bronchial and bronchiolar muscles and decreased histamine-induced lung resistance in the anaesthetised guinea pig. On some preparations the effects of the analogues were more pronounced than those of PGE1. The results suggest that some of the inter-m-phenylene analogues of PGE1 may be bronchodilators in asthmatics.     

海南木莲叶挥发油化学成分研究

目的：分析海南木莲叶的挥发油成分。方法：采用水蒸气法提取挥发油,气相色谱-质谱-计算机联用技术分析。结果：共鉴定出49种化合物,占挥发油总量的99．99％,其中主要成分是橙花叔醇（16．44％）;3,7-二甲基-2,6-辛二烯-1-醇（5.27％）;3,7-二甲基1,6-辛二烯-3-醇（5．12％）;α-丁香烯（4．97％）和丁香烯（4．48％）。     

Degradation of chlorinated guaiacols in anaerobic acetate enrichment conditions

Chlorinated guaiacols (4,5,6-trichloro-, 4,5-dichloro-, and 4-chloro-guaiacol) at 0.2 mM were completely degraded by anaerobic digester sludge within 4 d, but complete removal of TeCG could not be attained. The removal rates of chlorinated guaiacols by adsorption and biodegradation were in the following order: 4,5-dichloroguaiacol > 4-chloroguaiacol = 4,5,6-trichloroguaiacol > tetrachloroguaiacol. The most rapid initial TeCG degradation occurred in the glucose-supplemented cultures. However, the degradation rate of 4,5,6-TriCG was not increased significantly by supplementary glucose.