A novel metabolic pathway for degradation of 4-nonylphenol environmental contaminants by Sphingomonas xenophaga Bayram: ipso-hydroxylation and intramolecular rearrangement

Several nonylphenol isomers with alpha-quaternary carbon atoms serve as growth substrates for Sphingomonas xenophaga Bayram, whereas isomers containing hydrogen atoms at the alpha-carbon do not. Three metabolites of 4-(1-methyloctyl)-phenol were isolated in mg quantities from cultures of strain Bayram supplemented with the growth substrate isomer 4-(1-ethyl-1,4-dimethyl-pentyl)-phenol. They were unequivocally identified as 4-hydroxy-4-(1-methyl-octyl)-cyclohexa-2,5-dienone, 4-hydroxy-4-(1-methyl-octyl)-cyclohex-2-enone, and 2-(1-methyl-octyl)-benzene-1,4-diol by high pressure liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy. Furthermore, two metabolites originating from 4-n-nonylphenol were identified as 4-hydroxy-4-nonyl-cyclohexa-2,5-dienone and 4-hydroxy-4-nonyl-cyclohex-2-enone by high pressure liquid chromatography-mass spectrometry. We conclude that nonylphenols were initially hydroxylated at the ipso-position forming 4-alkyl-4-hydroxy-cyclohexa-2,5-dienones. Dienones originating from growth substrate nonylphenol isomers underwent a rearrangement that involved a 1,2-C,O shift of the alkyl moiety as a cation to the oxygen atom of the geminal hydroxy group yielding 4-alkoxyphenols, from which the alkyl moieties can be easily detached as alcohols by known mechanisms. Dienones originating from nongrowth substrates did not undergo such a rearrangement because the missing alkyl substituents at the alpha-carbon atom prevented stabilization of the putative alpha-carbocation. Instead they accumulated and subsequently underwent side reactions, such as 1,2-C,C shifts and dihydrogenations. The ipso-hydroxylation and the proposed 1,2-C,O shift constitute key steps in a novel pathway that enables bacteria to detach alpha-branched alkyl moieties of alkylphenols for utilization of the aromatic part as a carbon and energy source.     

Elucidation of the ipso-substitution mechanism for side-chain cleavage of alpha-quaternary 4-nonylphenols and 4-t-butoxyphenol in Sphingobium xenophagum Bayram

Recently we showed that degradation of several nonylphenol isomers with alpha-quaternary carbon atoms is initiated by ipso-hydroxylation in Sphingobium xenophagum Bayram (F. L. P. Gabriel, A. Heidlberger, D. Rentsch, W. Giger, K. Guenther, and H.-P. E. Kohler, J. Biol. Chem. 280:15526-15533, 2005). Here, we demonstrate with 18O-labeling experiments that the ipso-hydroxy group was derived from molecular oxygen and that, in the major pathway for cleavage of the alkyl moiety, the resulting nonanol metabolite contained an oxygen atom originating from water and not from the ipso-hydroxy group, as was previously assumed. Our results clearly show that the alkyl cation derived from the alpha-quaternary nonylphenol 4-(1-ethyl-1,4-dimethyl-pentyl)-phenol through ipso-hydroxylation and subsequent dissociation of the 4-alkyl-4-hydroxy-cyclohexadienone intermediate preferentially combines with a molecule of water to yield the corresponding alcohol and hydroquinone. However, the metabolism of certain alpha,alpha-dimethyl-substituted nonylphenols appears to also involve a reaction of the cation with the ipso-hydroxy group to form the corresponding 4-alkoxyphenols. Growth, oxygen uptake, and 18O-labeling experiments clearly indicate that strain Bayram metabolized 4-t-butoxyphenol by ipso-hydroxylation to a hemiketal followed by spontaneous dissociation to the corresponding alcohol and p-quinone. Hydroquinone effected high oxygen uptake in assays with induced resting cells as well as in assays with cell extracts. This further corroborates the role of hydroquinone as the ring cleavage intermediate during degradation of 4-nonylphenols and 4-alkoxyphenols.     

Elucidation of the ipso-Substitution Mechanism for Side-Chain Cleavage of α-Quaternary 4-Nonylphenols and 4-t-Butoxyphenol in Sphingobium xenophagum Bayram

Recently we showed that degradation of several nonylphenol isomers with α-quaternary carbon atoms is initiated by ipso-hydroxylation in Sphingobium xenophagum Bayram (F. L. P. Gabriel, A. Heidlberger, D. Rentsch, W. Giger, K. Guenther, and H.-P. E. Kohler, J. Biol. Chem. 280:15526-15533, 2005). Here, we demonstrate with ¹⁸O-labeling experiments that the ipso-hydroxy group was derived from molecular oxygen and that, in the major pathway for cleavage of the alkyl moiety, the resulting nonanol metabolite contained an oxygen atom originating from water and not from the ipso-hydroxy group, as was previously assumed. Our results clearly show that the alkyl cation derived from the α-quaternary nonylphenol 4-(1-ethyl-1,4-dimethyl-pentyl)-phenol through ipso-hydroxylation and subsequent dissociation of the 4-alkyl-4-hydroxy-cyclohexadienone intermediate preferentially combines with a molecule of water to yield the corresponding alcohol and hydroquinone. However, the metabolism of certain α,α-dimethyl-substituted nonylphenols appears to also involve a reaction of the cation with the ipso-hydroxy group to form the corresponding 4-alkoxyphenols. Growth, oxygen uptake, and ¹⁸O-labeling experiments clearly indicate that strain Bayram metabolized 4-t-butoxyphenol by ipso-hydroxylation to a hemiketal followed by spontaneous dissociation to the corresponding alcohol and p-quinone. Hydroquinone effected high oxygen uptake in assays with induced resting cells as well as in assays with cell extracts. This further corroborates the role of hydroquinone as the ring cleavage intermediate during degradation of 4-nonylphenols and 4-alkoxyphenols.     

Detection and mass spectrometric characterization of novel long-term dehydrochloromethyltestosterone metabolites in human urine

The biotransformation of dehydrochloromethyltestosterone (DHCMT, 4-chloro-17β-hydroxy,17α-methylandrosta-1,4-dien-3-one) in man was studied with the aim to discover long-term metabolites valuable for the antidoping analysis. Having applied a high performance liquid chromatography for the fractionation of urinary extract obtained from the pool of several DHCMT positive urines, about 50 metabolites were found. Most of these metabolites were included in the GC-MS/MS screening method, which was subsequently applied to analyze the post-administration and routine doping control samples. As a result of this study, 6 new long-term metabolites were identified tentatively characterized using GC-MS and GC-MS/MS as 4-chloro-17α-methyl-5β-androstan-3α,16,17β-triol (M1), 4-chloro-18-nor-17β-hydroxymethyl,17α-methyl-5β-androsta-1,13-dien-3α-ol (M2), 4-chloro-18-nor-17β-hydroxymethyl,17α-methyl-5β-androst-13-en-3α-ol (M3), its epimer 4-chloro-18-nor-17α-hydroxymethyl,17β-methyl-5β-androst-13-en-3α-ol, 4-chloro-18-nor-17β-hydroxymethyl,17α-methylandrosta-4,13-dien-3α-ol (M4) and its epimer 4-chloro-18-nor-17α-hydroxymethyl,17β-methylandrosta-4,13-dien-3α-ol. The most long-term metabolite M3 was shown to be superior in the majority of cases to the other known DHCMT metabolites, such as 4-chloro-18-nor-17β-hydroxymethyl,17α-methylandrosta-1,4,13-trien-3-one and 4-chloro-3α,6β,17β-trihydroxy-17α-methyl-5β-androst-1-en-16-one.     

Biotransformation of dianabol with the filamentous fungi and β-glucuronidase inhibitory activity of resulting metabolites

Biotransformation of the anabolic steroid dianabol (1) by suspended-cell cultures of the filamentous fungi Cunninghamella elegans and Macrophomina phaseolina was studied. Incubation of 1 with C. elegans yielded five hydroxylated metabolites 2–6, while M. phaseolina transformed compound 1 into polar metabolites 7–11. These metabolites were identified as 6β,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (2), 15α,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (3), 11α,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (4), 6β,12β,17β-trihydroxy-17α-methylandrost-1,4-dien-3-one (5), 6β,15α,17β-trihydroxy-17α-methylandrost-1,4-dien-3-one (6), 17β-hydroxy-17α-methylandrost-1,4-dien-3,6-dione (7), 7β,17β,-dihydroxy-17α-methylandrost-1,4-dien-3-one (8), 15β,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (9), 17β-hydroxy-17α-methylandrost-1,4-dien-3,11-dione (10), and 11β,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one (11). Metabolite 3 was also transformed chemically into diketone 12 and oximes 13, and 14. Compounds 6 and 12–14 were identified as new derivatives of dianabol (1). The structures of all transformed products were deduced on the basis of spectral analyses. Compounds 1–14 were evaluated for β-glucuronidase enzyme inhibitory activity. Compounds 7, 13, and 14 showed a strong inhibition of β-glucuronidase enzyme, with IC₅₀ values between 49.0 and 84.9 μM.     

Determination of diarylheptanoids from Alpinia officinarum (Lesser Galangal) by HPLC with photodiode array and electrochemical detection

Normal-phase column chromatography followed by semi-preparative reversed-phase HPLC has been used to isolate, from the rhizomes of Alpinia officinarum, five diarylheptanoids identified as 5-hydroxy-7-(4"-hydroxy-3"-methoxyphenyl)-1-phenyl-3-heptanone, 5-methoxy-7-(4"-hydroxy-3"-methoxyphenyl)-1-phenyl-3-heptanone, 7-(4"-hydroxyphenyl)-1-phenylhept-4-en-3-one, 7-(4"-hydroxy-3"-methoxyphenyl)-1-phenyl-hept-4-en-3-one, 1,7-diphenylhept-4-en-3-one. The levels of these five diarylheptanoids in root material were determined quantitatively by HPLC with UV detection and the assay methods so developed were simple, rapid and accurate. Four of the diarylheptanoids could also be detected by HPLC with electrochemical detection (ECD) in the oxidative mode, and ECD was found to have a higher sensitivity than photodiode array detection.     

Microbial transformation of 3β-acetoxypregna-5,16-diene-20-one by Penicillium citrinum

The biotransformation of 3β-acetoxypregna-5,16-diene-20-one (1) by using a filamentous fungus Penicillium citrinum resulted in the production of four metabolites 2–5. The structures of these compounds were elucidated by different spectroscopic analysis (1D- and 2D-NMR) and HR-ESI-MS as 3β,7β-dihydroxy-pregn-5,16(17)-dien-20-one (2), 3β-hydroxy-7α-methoxy-pregn-5,16(17)-dien-20-one (3), 3β,7β,11α-trihydroxy-pregn-5,16(17)-dien-20-one (4), and a known 3β,7α-dihydroxy-pregn-5,16(17)-dien-20-one (5). The 7-O-methylation is a novel reaction in the field of microbial transformation of pregnane steroids.     

Metabolism of metandienone in man: identification and synthesis of conjugated excreted urinary metabolites, determination of excretion rates and gas chromatographic-mass spectrometric identification of bis-hydroxylated metabolites

After oral administration of metandienone (17 alpha-methyl-androsta-1,4-dien-17 beta-ol-3-one) to male volunteers conjugated metabolites are isolated from urine via XAD-2-adsorption, enzymatic hydrolysis and preparative high-performance liquid chromatography (HPLC). Four conjugated metabolites are identified by gas chromatography-mass spectrometry (GC/MS) with electron impact (EI)-ionization after derivatization with N-methyl-N-trimethyl-silyl-trifluoroacetamide/trimethylsilyl-imidazole (MSTFA/TMS-Imi) and comparison with synthesized reference compounds: 17 alpha-methyl-5 beta-androst-1-en-17 beta-ol-3-one (II), 17 alpha-methyl-5 beta-androst-1-ene-3 alpha,17 beta-diol (III), 17 beta-methyl-5 beta-androst-1-ene-3 alpha,17 alpha-diol (IV) and 17 alpha-methyl-5 beta-androstane-3 alpha,17 beta-diol (V). After administration of 40 mg of metandienone four bis-hydroxy-metabolites--6 beta,12-dihydroxy-metandienone (IX), 6 beta,16 beta-dihydroxy-metandienone (X), 6 beta,16 alpha-dihydroxy-metandienone (XI) and 6 beta,16 beta-dihydroxy-17-epimetandienone (XII)--were detected in the unconjugated fraction. The metabolites III, IV and V are excreted in a comparable amount to the unconjugated excreted metabolites 17-epimetandienone (VI), 6 beta-hydroxy-metandienone (VII) and 6 beta-hydroxy-17-epimetandienone (VIII). Whereas the unconjugated excreted metabolites show maximum excretion rates between 4 and 12 h after administration the conjugated metabolites III, IV and V are excreted with maximum rates between 12 and 34 h.     

Chemical constituents of rice (Oryza sativa) hulls and their herbicidal activity against duckweed (Lemna paucicostata Hegelm 381)

Four new compounds, stigmastanol-3beta-p-glyceroxydihydrocoumaroate (1), stigmastanol-3beta-p-butanoxydihydrocoumaroate (2), lanast-7,9(11)-dien-3alpha,15alpha-diol-3alpha-D-glucofuranoside (3) and 1-phenyl-2-hydroxy-3,7-dimethyl-11-aldehydic-tetradecane-2-beta-D-glucopyranoside (4), along with several known compounds were isolated from the methanol extract of hulls of Oryza sativa. The new structures were established by one- and two-dimensional NMR and in combination with IR, EI/MS, FAB/MS and HR-FAB/ MS. Compound (3) strongly inhibited the growth of duckweed (Lemna paucicostata Hegelm 381), whilst compounds (2) and (4) exhibited weak inhibition.     

Neolignans from Aniba lancifolia

The branches of the shrub Aniba lancifolia Kubitzki et Rodrigues (Lauraceae) contain besides 2-hydroxy-4,5- dimethoxyallylbenzene and its dimer cyclohexan-2-allyl- 5-en-4,5-dimethoxy-4-O-(2′-allyl-4′,5′-dimethoxyphenyl)-1-one (lancilin, 2) 6 further novel neolignans: (4S,2′R)- and (4R,2′E)-cyclohexan-2-allyl-2,5-dien-4,5-dimethoxy-4-[2′-(1′-guaiacyl)-propyl]-1-one (lancifolins A and B, 3a and 3b), (4S,2′R)- and (4R,2′R)-cyclohexan- 2-allyl-2,5-dien-4,5-dimethoxy-4-[2′-(1′-veratryl)-propyl]-1-one (lancifolins C and D, 3c and 3d), (4S,2′R)-and (4R,2′R)-cyclohexan-2-allyl-2,5-dien-4,5-dimethoxy-4-[2′-(1′-piperonyl)-propyl]-1-one (lancifolins E and F, 3e and 3f).     

Two new resorcinol derivatives with strong cytotoxicity from the roots of Ardisia brevicaulis Diels

Two new resorcinol derivatives, 4-hydroxy-2-methoxy-6-[(8Z)-pentadec-8-en-1-yl]phenyl acetate (1) and 4-hydroxy-2-methoxy-6-pentadecylphenyl acetate (2), together with known compounds ardisiphenol D (3), 5-tridecylresorcinol (4), 5-pentadecylresorcinol (5), 5-[(8Z)-pentadec-8-en-1-yl]resorcinol (6), belamcandaquinones C and D (7 and 8, resp.), ardisicrenoside A, ardisiacrispin B, (22E)-24-ethyl-5α-cholesta-7,22-dien-3-one, and (22E)-24-ethyl-5α-cholesta-7,22-dien-3β-ol were isolated from the MeOH extract of the roots of Ardisia brevicaulis Diels. Their structures were determined by spectroscopic analysis including ESI- and EI-MS, and NMR data. Cytotoxicities of 1-4 against cell lines A549, MCF-7, and PANC-1 were tested in vitro by the MTT (=3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) method. Compounds 1-4 showed cytotoxic activity against all cell lines stronger than that of cisplatin against A549.     

Degradation characteristics and metabolic pathway of 17β-estradiol (E2) by <Emphasis Type="Italic">Rhodococcus sp. DS201</Emphasis>

In this study an E2-degrading bacterium was isolated from the activated sludge of a municipal treatment plant that treats the waste from a contraceptive medicine-processing factory in Beijing, China. Using the observed morphological and physiological features of the bacterium and 16S rRNA sequence analysis, this bacterial strain was identified as Rhodococcus sp. DS201. Using single-factor experiments and orthogonal tests, it was demonstrated that, when strain DS210 bacteria were inoculated into MM medium at an initial concentration of 1 mg/L with an initial pH of 7 and an inoculum amount of 1%, complete degradation of E2 by this strain was achieved within 3 days at 30oC. After strain DS201 had degraded the E2, several E2 metabolites were detected in the culture extracts using high-performance liquid chromatography (HPLC); they were then further identified using HPLC with tandem mass spectrometry (LC-MS/MS). Mass spectrum analysis of the E2 degradation identified the following products: pent-4-enoic acid; 2-ethyl-3-hydroxy-6-methylcyclohexane-1-carboxylic acid; 3-(7a-methyl-1,5-dioxooctahydro-1H-inden-4-yl) propanoic acid; and 5-hydroxy-4-(3-hydroxypropyl)-7a-methyloctahydro-1H-inden-1-one. These products have not previously been reported as parts of a mechanism for microbial E2 degradation and were suspected to be new metabolite products. Therefore, the E2 degradation pathway by strain DS201 is proposed herein.     

Hydroxylated 2-amino-3H-phenoxazin-3-one derivatives as products of 2-hydroxy-1,4-benzoxazin-3-one (HBOA) biotransformation by Chaetosphaeria sp., an endophytic fungus from Aphelandra tetragona

The biotransformation of the phytoanticipin HBOA and its major degradation metabolites 2-hydroxy-N-(2-hydroxyphenyl)acetamide (7) and N-(2-hydroxyphenyl)acetamide (8) by Chaetosphaeria sp., an endophytic fungus isolated from Aphelandra tetragona, was studied. Three new metabolites could be identified as 2-amino-7-hydroxy-3H-phenoxazin-3-one (12), 2-acetylamino-7-hydroxy-3H-phenoxazin-3-one (13) and 7-hydroxy-2-(2-hydroxyacetyl)-amino-3H-phenoxazin-3-one (14). Structure elucidation of 12 and 13 was performed by MS, 1H, 13C NMR and 2D NMR techniques and confirmed by chemical transformation.     

Enzymatic reduction of shogaol: a novel biotransformation pathway for the alpha,beta-unsaturated ketone system.

A novel reductive metabolism of 1-(4-hydroxy-3-methoxyphenyl)-deca-4-ene-3-one (shogaol), a pungent principle of ginger, was investigated in rat liver in vitro. Ethyl acetate-extractable metabolites of shogaol formed by incubation of this alpha,beta-unsaturated ketone with rat liver cytosolic fraction fortified with NADPH or NADPH-generating system were isolated, and two major metabolites were identified as 1-(4-hydroxy-3-methoxyphenyl)-decan-3-one (paradol) and 1-(4-hydroxy-3-methoxy)-decan-3-ol (reduced paradol). 1-(4-hydroxy-3-methoxyphenyl)-deca-1-ene-3-one (dehydroparadol), a non-pungent analog of shogaol, formed the same metabolites as did shogaol under similar incubation conditions. Paradol appears to be an intermediate in the reductive metabolism of the alpha,beta-unsaturated ketone moiety of shogaol to the corresponding saturated alcohol.     

Antifungal isopimaranes from Hypoestes serpens

Five isopimarane diterpenes (7beta-hydroxyisopimara-8,15-dien-14-one, 14alpha-hydroxyisopimara-7,15-dien-1-one, 1beta,14alpha-dihydroxyisopimara-7,15-diene, 7beta-hydroxyisopimara-8(14),15-dien-1-one and 7beta-acetoxyisopimara-8(14),15-dien-1-one) have been isolated from the leaves of Hypoestes serpens (Acanthaceae). All compounds exhibited antifungal activity against both the plant pathogenic fungus Cladosporium cucumerinum and the yeast Candida albicans; two of them also displayed an acetylcholinesterase inhibition. The structures of the compounds were determined by means of spectrometric methods, including 1D and 2D NMR experiments and MS analysis.     

New monoterpenoid by biotransformation of thymoquinone using Aspergillus niger

Microbial transformation of thymoquinone (5-isopropyl-2-methyl-cyclohexa-2,5-diene-1,4-dione) (1) by suspended cell-cultures of the plant pathogenic fungus Aspergillus niger resulted in the production of three metabolites. These metabolites were identified as 5-isopropyl-2-methyloxepin-1-one (2), 3-hydroxy-5-isopropyl-2-methylcyclohexa-2,5-diene-1,4-dione (3), and 5-isopropyl-2-methylbenzene-1,4-diol (4) by different spectroscopic methods. Metabolite 2 was found to be a new compound. Compound 4 showed a potent antioxidant activity.     

Analysis of n-hexane, 2-hexanone, 2,5-hexanedione, and related chemicals by capillary gas chromatography and high-performance liquid chromatography

Analytical methods, using capillary gas chromatography and normal-phase high-performance liquid chromatography, were developed for the analysis of the neurotoxic chemicals n-hexane, 2-hexanone, and 2,5-hexanedione and their suspected metabolites. Two gas chromatographic methods, using a 50-m glass capillary OV 101 column and cyclohexane as an internal standard, were employed. In both methods, the injector and detector temperatures were 220 and 280 degrees C, respectively. In method I the following temperature program was used: isothermic at 50 degrees C for 30 min, followed by a temperature increase of 10 degrees C/min to a final temperature of 180 degrees C, which was then maintained for 7 min. This method was used to analyze the following compounds: n-hexane, 2,5-dimethylfuran, 2-hexanone, 3-hexanone, hexanal, 1-hexanol, 2-hexanol, 3-hexanol, 5-hydroxy-2-hexanone, gamma-valerolactone, 2,5-hexanedione, and 2,5-hexanediol. Method II, which was developed for n-hexane and eight of its more common metabolites, used the following temperature program: isothermic at 70 degrees C for 15 min, followed by a temperature increase of 40 degrees C/min to a final temperature of 220 degrees C, which was maintained for 5 min. A linear relationship between peak area and amount injected was observed over a 100-fold range. The minimum detectable amounts ranged from 0.05 to 1 microgram, depending on the compound. Normal-phase HPLC, using a 5-micron silica cartridge fitted into an RCM-100 radial-compression separation system, was utilized to analyze 2-hexanone and its metabolites 2,5-dimethylfuran, gamma-valerolactone, 5-hydroxy-2-hexanone, and 2,5-hexanedione.(ABSTRACT TRUNCATED AT 250 WORDS)     

Microbial transformation of 17α-cyanomethyl-17-hydroxy-4,9-estradien-3-one (STS 557) and 17α-cyanomethyl-19-nortestosterone by Mycobacterium smegmatis

Microbial transformation of the new progestagen STS 557 (17α-cyanomethyl-17-hydroxy-4,9-estradien-3-one) by $\text{Mycobacterium smegmatis}$ yielded predominantly ring A-aromatized compounds: 17α-cyanomethyl-1,3,5(10),9(11)-estratetraene-3, 17-diol, 17α-cyanomethyl-1,3,5(10)-estratriene-3, 17-diol and the corresponding 3-methyl ethers. The analogous compound without the 9(10) double bond, 17α-cyanomethyl-19-nortestosterone, was transformed mainly to 5α-hydrogenated metabolites: 17α-cyanomethyl-17-hydroxy-5α-estran-3-one, 17α-cyanomethyl-17-hydroxy-5α-1-estren-3-one, 17α-cyanomethyl-5α-estrane-3α, 17-diol, and 17α-cyanomethyl-5α-estrane-3β, 17-diol. From these results, it is concluded that 4,9-dien-3-oxo compounds are not substrates for enzymatic 5α-hydrogenation.     

Antiprogestational agents. The synthesis of 7-alkyl steroidal ketones with anti-implantational and antidecidual activity

A series of 7α- and 7β- alkyl derivatives of steroidal 4-en- and 5-en-3-ones were prepared by 1,6-conjugate addition of organocopper reagents to various steroidal 4,6-dien-3-ones of the androstane, estrane and gonane series. Biological study of these and related compounds revealed that 17β-hydroxy-7α-methyl-5-androsten-3-one (2), 17β-hydroxy-7α-methyl-5-estren-3-one acetate and 17β-hydroxy-7α-methyl-4-estren-3-one acetate had significant anti-implantational and antidecidual activities. The contragestative effects were associated with the latter antihormonal properties, and not with the androgenicity of these compounds.     

New polyoxygenated steroids from the Antarctic octocoral Dasystenella acanthina

The chemical study of the Antarctic octocoral Dasystenella acanthina has led to the isolation of the new polyoxygenated steroids (24R,22E)-24-hydroxycholest-4,22-dien-3-one (1), 23-acetoxy-24,25-epoxycholest-4-en-3-one (2), 12beta-acetoxycholest-4-en-3,24-dione (3), 12beta-acetoxy-24,25-epoxycholest-4-en-3-one (4), (22E)-25-hydroxy-24-norcholest-4,22-dien-3-one (5), 3alpha-acetoxy-25-hydroxycholest-4-en-6-one (6), and 3alpha,11alpha-diacetoxy-25-hydroxycholest-4-en-6-one (7), whose structures have been established by spectroscopic analysis. The absolute stereochemistry at C-24 in compound 1 has been determined through the 1H NMR study of the corresponding (R)- and (S)-MPA esters. All the new compounds showed significant activities as growth inhibitors of several human tumor cell lines. In addition, cytostatic and cytotoxic effects were also observed on selected tumor cell lines.