Synthesis and antibacterial properties of new N4-acetylated hexahydro-2,7-dioxopyrido[2,3-f]quinoxaline-8-carboxylic acids

Direct interaction between 7-chloro-1-cyclopropyl-6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid and primary α-amino acids (exemplified by glycine, alanine, and l-valine) in aqueous ethanolic NaHCO₃ at 70–80°C for 24–72?h produced the respective N-(4-oxoquinolin-7-yl)-α-amino acids (6a–c). The latter derivatives underwent reductive lactamization upon treatment with Na₂S₂O₄ in aqueous ethanol to afford moderate yields of the corresponding pyrido[2,3-f]quinoxaline-8-carboxylic acids (8a–c). Acetylation of 8a–c using acetyl chloride afforded N₄-acetylated hexahydro-2,7-dioxopyrido[2,3-f]quinoxaline-8-carboxylic acids (9a–c). The structures, assigned to these new heterocyclic products, are supported by analytical and spectral data. The synthesized compounds (6a–c/9a–c) showed appreciable antibacterial activity as compared with ciprofloxacin.     

Novel ofloxacin derivatives: synthesis, antimycobacterial and toxicological evaluation

Thirty novel 9-fluoro-2,3-dihydro-8,10-(mono/di-sub)-3-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acids were synthesized from 2,3,4,5-tetrafluoro benzoic acid and evaluated for in vitro and in vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC(2)) and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from mycobacteria. Among the synthesized compounds, 10-[2-carboxy-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl]-9-fluoro-2,3-dihydro-3-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid was found to be the most active compound in vitro with MIC99 of 0.19 microM and 0.09 microM against MTB and MTR-TB, respectively. In the in vivo animal model also the same compound decreased the bacterial load in lung and spleen tissues with 1.91 and 2.91--log10 protections, respectively, at the dose of 50mg/kg body weight. Compound 10-[(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)]-9-fluoro-2,3-dihydro-3-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid was found to be the most active in the inhibition of the supercoiling activity of DNA gyrase with an IC(50) of 10.0 microg/mL. The results demonstrate the potential and importance of developing new oxazino quinolone derivatives against mycobacterial infections.     

Synthesis and biological evaluation of tetracyclic thienopyridones as antibacterial and antitumor agents

A facile synthesis of model 4-oxopyrido[3',2':4,5]thieno[3,2-b]indole-3-carboxylic acids 9a-e was achieved via Stille arylation of 2-chloro-3-nitro-4-oxothieno[2,3-b]pyridine-5-carboxylate and a subsequent microwave-assisted phosphite-mediated Cadogan reaction. The new compounds were tested for their in vitro antimicrobial and antiproliferative activity. Compounds 9a-c and 9e exhibited very high potency against Gram positive Bacillus subtilis and Bacillus megaterium at concentrations 0.000015-0.007 μg/mL. They also displayed excellent activity towards other Gram positive bacilli and staphylococci and Gram negative Haemophilus influenzae, being in most cases superior or equal to commercial fluoroquinolones. Both 9a and 9c were inhibitors of the DNA gyrase activity. As concerns antitumor properties, compounds 9b-e showed growth inhibition of MCF-7 breast tumor and A549 non-small cell lung cancer cells with IC(50) 1.6-2.8 μM and 2.6-6.9 μM, respectively, coupled with absence of cytotoxicity towards normal cells. These compounds are promising as dual acting chemotherapeutics.     

Novel anellated pyrazoloquinolin-3-ones: synthesis and in vitro BZR activity

A series of pyrazolo[4,3-c]pyrrolo[3,2-f]quinolin-3-one derivatives 6, 7a-c, 8a,b, 9a,b and 10-12 were synthesized as modified pyrazoloquinolinone analogs (PQs) and evaluated for their ability to inhibit radioligand to central and peripheral benzodiazepine receptors (BZRs) and their effect on GABA(A) alpha1beta2gamma2L receptors expressed in Xenopus laevis oocytes. Multistep synthesis starting from 5-nitroindole, via the Gould-Jacobs reaction to the quinoline nucleus, yielded key intermediates 9-chloro-3H-pyrrolo[3,2-f]quinoline-8-carboxylates. The reaction of the latter with methyl-hydrazine and various phenyl-hydrazines furnished the final compounds. In order to confirm the expected tetracyclic 2-substituted-2H-pyrazolopyrroloquinolin-3-one structure, IR spectrophotometric, mono-1H and 13C and bi-dimensional spectrometric and HRMS analyses were carried out: all compounds were found to be 2-substituted 3-keto tautomers; compound 6 only differed because it turned out to be 1-methyl-2H-pyrazolo[4,3-c]pyrrolo[3,2-f]quinolin-3-olo. The results of this work are consistent with those previously reported for PQs: 7-9 show high potency in displacing specific [3H]flunitrazepam from its receptor site; no compound was active in inhibiting the binding of [3H]PK 11195. They all act as antagonists at central BZR.     

Synthesis and cytotoxicity evaluation of pyridin[2,3-f]indole-2,4,9-trione and benz[f]indole-2,4,9-trione derivatives

3-Ethoxycarbonyl-3-methyl-1N-substrituted-2,3-dihydro-pyridin[2,3-f]indole-2,4,9-trione [9(a-d)] and 3-ethoxycarbonyl-3-methyl-N-substrituted-2,3-dihydro-benz[f]indole-2,4,9-trione [10(a-i)] derivatives were synthesized from 7-chloro-6-(1,1-diethoxycarbonyl-ethyl)-5,8-quinolinedione (7) and 2-chloro-3-(1,1-diethoxycarbonyl-ethyl)-1,4-naphthoquinone (8), respectively, using a variety of alkyl- and arylamines. The cytotoxic activities of the synthesized compounds were evaluated by a Sulforhodamine B (SRB) assay against the following tumor cell lines: A459 (human non-small cell lung), SK-OV-3 (human ovarian), SK-MEL-2 (human melanoma), XF498 (human CNS), and HCT 15 (human colon). Almost all the derivatives mentioned above had a more potent cytotoxic effect against SK-OV-3 than etoposide. In particular, 3-ethoxycarbonyl-3-methyl-N-(4-aminophenyl)-2,3-dihydro-benz[f]indole-2,4,9-trione (10h) exhibited greater activity against all the tumor cell lines, and its cytotoxic effect against SK-OV-3 was especially higher than doxorubicin.     

Synthesis and bioactivity of 4,10-dimethyl-pyridino[2,3-h]quinolin-2(1H)-one-9-carboxylic acid and its esters

4,10-Dimethyl-pyridino[2,3-h]quinolin-2(1H)-one-9-carboxylic acid (1) was synthesized by a new approach via the key intermediate 7-[1-aza-2-(dimethylamino)vinyl]-4-methylquinolin-2(1H)-one (4). Compound 1 and its esters were evaluated in cytotoxicity and anti-HIV assays. The 9-carboxyl (1s)-endo-(-)-borneol ester (9) showed marginal cytotoxic activity in CAK1-1, HOS, KB, and HCT-8 cells.     

Synthesis of pyridino[2,3-f]indole-4,9-dione and 6,7-disubstituted quinoline-5,8-dione derivatives and evaluation on their cytotoxic activity

We report upon the synthesis of the following derivatives: N-substituted-pyridino[2,3-f]indole-4,9-dione, and 6-(alpha-diethoxycarbonyl-methyl)-7-substituted-amino-quinoline-5,8-dione, which contain the active quinoline-5,8-dione (VII) moiety. The cytotoxic activities of these compounds have been tested in SRB (SulfoRhodamine B) assays against the cancer cell lines of A-549 (human lung cancer), SK-MEL-2 (human melanoma cancer), SK-OV-3 (human ovarian cancer), XF-498 (human brain cancer) and HCT 15 (human colon cancer). The compound, N-benzyl-3-ethoxycarbonyl-2-hydroxy-pyridino[2,3-f]indole-4,9-dione (A-9), also showed higher activity than cis-platin. The highest level of cytotoxic activity in these human tumor cell lines was observed in the compound 6-(alpha-diethoxycarbonyl-methyl)-7-(2-methyl-phenylamino)-quinoline-5,8-dione (B-3).     

Phytotoxic naphthopyranone derivatives from the coprophilous fungus Guanomyces polythrix.

Reinvestigation of the fermentation broth and mycelium of the coprophilous fungus Guanomyces polythrix, grown in static conditions, led to the isolation of several phytotoxic compounds, including two new naphthopyranone derivatives, namely (2S, 3R)-5-hydroxy-6,8-dimethoxy-2,3-dimethyl-2,3-dihydro-4H-naphtho[2,3-b]-pyran-4-one and (2S, 3R)-5-hydroxy-6,8,10-trimethoxy-2,3-dimethyl-2,3-dihydro-4H-naphtho[2,3-b]-pyran-4-one. The structures of the new compounds were established by spectral and chiroptical methods. In addition, the structure of 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylic acid methyl ester was unambiguously determined by X-ray analysis. The isolates caused significant inhibition of radicle growth of two weed seedlings (Amaranthus hypochondriacus and Echinochloa crusgalli) and interacted with both spinach and bovine brain calmodulins.     

Design, synthesis, biological evaluation and X-ray crystal structure of novel classical 6,5,6-tricyclic benzo[4,5]thieno[2,3-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors

Classical antifolates (4-7) with a tricyclic benzo[4,5]thieno[2,3-d]pyrimidine scaffold and a flexible and rigid benzoylglutamate were synthesized as dual thymidylate synthase (TS) and dihydrofolate reductase (DHFR) inhibitors. Oxidative aromatization of ethyl 2-amino-4-methyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate (±)-9 to ethyl 2-amino-4-methyl-1-benzothiophene-3-carboxylate 10 with 10% Pd/C was a key synthetic step. Compounds with 2-CH? substituents inhibited human (h) TS (IC?? =0.26-0.8 μM), but not hDHFR. Substitution of the 2-CH? with a 2-NH? increases hTS inhibition by more than 10-fold and also affords excellent hDHFR inhibition (IC?? = 0.09-0.1 μM). This study shows that the tricyclic benzo[4,5]thieno[2,3-d]pyrimidine scaffold is highly conducive to single hTS or dual hTS-hDHFR inhibition depending on the 2-position substituents. The X-ray crystal structures of 6 and 7 with hDHFR reveal, for the first time, that tricyclics 6 and 7 bind with the benzo[4,5]thieno[2,3-d]pyrimidine ring in the folate binding mode with the thieno S mimicking the 4-amino of methotrexate.     

Chemical modification of aryl-1,2,3,6-tetrahydropyridinopyrimidine derivative to discover corticotropin-releasing factor(1) receptor antagonists: aryl-1,2,3,6-tetrahydropyridino-purine, -3H-1,2,3-triazolo[4,5-d)pyrimidine, -purin-8-one, and -7H-pyrrolo[2,3-d]pyrimidine derivatives

Structure-affinity relationships (SARs) of non-peptide CRF(1) antagonists suggest that such antagonists can be constructed of three units: a hydrophobic unit (Up-Area), a proton accepting unit (Central-Area), and an aromatic unit (Down-Area). Recently, various non-peptide corticotropin-releasing factor(1) (CRF(1)) receptor antagonists obtained by modification of the Central-Area have been reported. In contrast, we modified the Up-Area and presented 4- or 5-aryl-1,2,3,6-tetrahydropyridinopyrimidine derivatives including potent CRF receptor ligands 1a-c, and proposed that the 4- or 5-aryl-1,2,3,6-tetrahydropyridino moiety might be useful as a substituent in the Up-Area. Our interest shifted to the chemical modification in which the pyrimidine ring of 1a-c was replaced by other heterocycles, purine ring of 2, 3H-1,2,3-triazolo[4,5-d]pyrimidine ring of 3, purin-8-one ring of 4 and 7H-pyrrolo[2,3-d]pyrimidine ring of 5. Among them, 5-aryl-1,2,3,6-tetrahydropyridinopurine compound 6j (CRA0186) had the highest affinity for CRF(1) receptors (IC(50)=20nM). We report here the synthesis and SARs of derivatives 6-9.     

Alkaloids from Portulaca oleracea L

Five alkaloids (oleraceins A, B, C, D and E) were isolated from Portulaca oleracea L., and their structures determined by spectroscopic methods as 5-hydroxy-1-p-coumaric acyl-2,3-dihydro-1H-indole-2-carboxylic acid-6-O-beta-D-glucopyranoside, 5-hydroxy-1-ferulic acyl-2,3-dihydro-1H-indole-2-carboxylic acid-6-O-beta-D-glucopyranoside, 5-hydroxy-1-(p-coumaric acyl-7'-O-beta-D-glucopyranose)-2,3-dihydro-1H-indole-2-carboxylic acid-6-O-beta-D-glucopyranoside, 5-hydroxy-1-(ferulic acyl-7'-O-beta-D-glucopyranose)-2,3-dihydro-1H-indole-2-carboxylic acid-6-O-beta-D-glucopyranoside and 8,9-dihydroxy-1,5,6,10b-tetrahydro-2H-pyrrolo[2,1-a]isoquinolin-3-one, respectively.     

Synthesis of base substituted 2-hydroxy-3-(purin-9-yl)-propanoic acids and 4-(purin-9-yl)-3-butenoic acids

Alkylation of 6-chloropurine and 2-amino-6-chloropurine with bromoacetaldehyde diethyl acetal afforded 6-chloro-9-(2,2-diethoxyethyl)purine (3a) and its 2-amino congener (3b). Treatment of compounds 3 with primary and secondary amines gave the N6-substituted adenines (5a-5c) and 2,6-diaminopurines (5d-5f). Hydrolysis of 3 resulted in hypoxanthine (6a) and guanine (6b) derivatives, while their reaction with thiourea led to 6-sulfanylpurine (7a) and 2-amino-6-sulfanylpurine (7b) compounds. Treatment with diluted acid followed by potassium cyanide treatment and acid hydrolysis afforded 6-substituted 3-(purin-9-yl)- and 3-(2-aminopurin-9-yl)-2-hydroxypropanoic acids (8-10). Reaction of compounds 3 with malonic acid in aqueous solution gave exclusively the product of isomerisation, 6-substituted 4-(purin-9-yl)-3-butenoic acids (15).     

Biosynthesis of quinoxaline antibiotics: purification and characterization of the quinoxaline-2-carboxylic acid activating enzyme from Streptomyces triostinicus

A quinoxaline-2-carboxylic acid activating enzyme was purified to homogeneity from triostin-producing Streptomyces triostinicus. It could also be purified from quinomycin-producing Streptomyces echinatus. Triostins and quinomycins are peptide lactones that contain quinoxaline-2-carboxylic acid as chromophoric moiety. The enzyme catalyzes the ATP-pyrophosphate exchange reaction dependent on quinoxaline-2-carboxylic acid and the formation of the corresponding adenylate. Besides quinoxaline-2-carboxylic acid, the enzyme also catalyzes the formation of adenylates from quinoline-2-carboxylic acid and thieno[3,2-b]pyridine-5-carboxylic acid. No adenylates were seen from quinoline-3-carboxylic acid, quinoline-4-carboxylic acid, pyridine-2-carboxylic acid, and 2-pyrazinecarboxylic acid. Previous work [Gauvreau, D., & Waring, M. J. (1984) Can. J. Microbiol. 30, 439-450] revealed that quinoline-2-carboxylic acid and thieno[3,2-b]pyridine-5-carboxylic acid became efficiently incorporated into the corresponding quinoxaline antibiotic analogues in vivo. Together with the data described here, this suggests that the enzyme is part of the quinoxaline antibiotics synthesizing enzyme system. The enzyme displays a native molecular weight of 42,000, whereas in its denatured form it is a polypeptide of Mr 52,000-53,000. It resembles in its behavior actinomycin synthetase I, the chromophore activating enzyme involved in actinomycin biosynthesis [Keller, U., Kleinkauf, H., & Zocher, R. (1984) Biochemistry 23, 1479-1484].     

Two biflavonoids from Ouratea flava stem bark

In a chemical investigation on the stem bark of Ouratea flava, two biflavonoids: 1-[3-(2,4-dihydroxy-benzoyl)-4,5,6-trihydroxy-2-(4-hydroxy-phenyl)-benzofuran-7-yl] -3-(4-hydroxy-phenyl) -propenone (flavumone A) and 3-(2,4-dihydroxy-benzoyl)-4-hydroxy-2,7-bis-(4-hydroxy-phenyl) -7,8- dihydro-furo[2,3-f]chromen-9-on (flavumone B) were isolated along with five known flavonoids. Their structures were established by various analyses including 2D-NMR spectroscopy.     

Mutagenicity of some synthetic quinolines and quinoxalines related to IQ, MeIQ or MeIQx in Ames test

3-Methyl- and 3,4-dimethyl-3H-imidazo[4,5-f]quinoline, 3,8-dimethyl-3H-imidazo[4,5-f]quinoxaline, N6-methyl- and N6,7-dimethylquinoline-5,6-diamine, as well as N6,3-dimethylquinoxaline-5,6-diamine, have been synthesized. Only the first-mentioned compound was active in Ames test; the response was equal for Salmonella typhimurium TA98 and TA100, regardless of enzymatic activation (S9). However, its mutagenicity to TA98 + S9 was 300-1300 times smaller than the values reported for the related compounds, 3-methyl- and 3,4-dimethyl-3H-imidazo[4,5-f]quinolin-2-amine ('IQ' and 'MeIQ'), and for 3,8-dimethyl-3H-imidazo[4,5-f]quinoxalin-2-amine ('MeIQx'). Hence, the presence of the imidazole ring and the 2-amino group in the molecule seems to be important for the high mutagenicity of the latter compounds.     

Bacterial Transformations of Naphthothiophenes

Naphthothiophenes are minor components of fossil fuels, and they can enter the environment from oil spills. Naphtho[2,1-b]thiophene, naphtho[2,3-b]thiophene, and 1-methylnaphtho[2,1-b]thiophene were synthesized and used in biodegradation studies with 1-methylnaphthalene (1-MN)-degrading Pseudomonas strains W1, F, and BT1. Cultures were incubated with one of the naphthothiophenes with or without 1-MN, acidified, and extracted with CH(inf2)Cl(inf2). The extracts were analyzed by gas chromatography with flame photometric and mass detectors to characterize sulfur-containing metabolites and with an atomic emission detector for quantification. Only strain W1 was able to grow on naphtho[2,1-b]thiophene, but strains F and BT1 cometabolized this compound if 1-MN was present. 1-MN was required by all three strains to metabolize naphtho[2,3-b]thiophene, which was more resistant to biodegradation than the [2,1-b] isomer. Two metabolites of naphtho [2,1-b]thiophene were purified, analyzed by (sup1)H nuclear magnetic resonance spectroscopy, and found to be 4-hydroxybenzothiophene-5-carboxylic acid (metabolite I) and 5-hydroxybenzothiophene-4-carboxylic acid (metabolite II). In cultures of strain W1 grown for 7 days on 52 (mu)mol of naphtho[2,1-b]thiophene, >84% of the substrate was degraded and metabolites I and II accounted for 19 and 9%, respectively, of the original amount of naphtho[2,1-b]thiophene. When 1-MN was present, strain W1 degraded >97% of the naphtho[2,1-b]thiophene and similar amounts of metabolite II were produced, but metabolite I did not accumulate. 1-MN was shown to promote the further degradation of metabolite I, but not of metabolite II, by strain W1. Thus, 1-MN enhanced the biodegradation of naphtho[2,1-b]thiophene. Approximately 70% of the 1-methylnaphtho [2,1-b]thiophene added to cultures of strain W1 with 1-MN was recovered as 4-hydroxy-3-methylbenzothiophene-5-carboxylic acid, the 3-methyl analog of metabolite I. The methyl substitution hindered further metabolism of 3-methyl-metabolite I even in the presence of 1-MN. Cometabolism of naphtho[2,3-b]thiophene yielded two products that were tentatively identified as 5-hydroxybenzothiophene-6-carboxylic and 6-hydroxybenzothiophene-5-carboxylic acids.     

2,3-Dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid derivatives: a novel class of small molecule heparanase inhibitors

A novel class of 2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acids are described as inhibitors of the endo-beta-glucuronidase heparanase. Several of the compounds, for example, 2-[4-propylamino-5-[5-(4-chloro)phenyl-benzoxazol-2-yl]phenyl]-2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid (9c), display potent heparanase inhibitory activity (IC(50) 200-500 nM) and have high selectivity (>100-fold) over human beta-glucuronidase. They also show anti-angiogenic effects. Such compounds should serve as useful biological tools and may provide a basis for the design of novel therapeutic agents.     

Three isoflavanones with cannabinoid-like moieties from Desmodium canum

Three further derivatives of 5,7,2',4'-tetrahydroxy-6-methyl isoflavanone have been isolated from the root extract of Desmodium canum and assigned the structures 2,3-dihydro-5,7-dihydroxy-6-methyl-3-(1a,2,3,3a,8b,8c-hexahydro-6-hydroxy-1,1,3a-trimethyl-1H-4-oxabenzo[f]cyclobut[c,d]inden-7-yl)-4H-1-benzopyran-4-one (1) 2,3-dihydro-5,7-dihydroxy-6-methyl-3-(6a,7,8,10a-tetrahydro-3-hydroxy-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-2-yl)-4H-1-benzopyran-4-one (2) 2,3-dihydro-5,7-dihydroxy-6-methyl-3-(3-hydroxy-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-2-yl) 4H-1-benzopyran-4-one (3). The three compounds and the previously isolated chromene 4 all derive from the geranylated precursor 5 by a series of cannabinoid-like oxidative rearrangements.     

Synthesis and biological evaluation of some acyclic alpha-(1H-pyrazolo-[3,4-d]pyrimidin-4-yl)thioalkylamide nucleosides

The chemical synthesis of some acyclic alpha-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)thioalkylamide nucleosides (10-12)a-c is described. The treatment of IH-pyrazolo[3,4-d]pyrimidin-4-thione 1 with compounds 2a-c gave, regioselectively, ethyl alpha-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)thioalkylates 3a-c, respectively. These heterocycles were alkylated, separately, with alkylating agents 4, 5 and 6 to give, regioselectively, the N1-acyclic nucleosides (7-9)a-c which were deprotected to afford the desired products (10-12)a-c. All synthetic compounds were characterized on the basis of their physical and spectroscopic properties. The products (10-12)a-c were evaluated for their inhibitory effects against the replication of HIV-1 (III(B)), HIV-2 (ROD), various DNA viruses, a variety of tumor-cell lines and M. tuberculosis. No marked biological activity was found.     

Isolation and structure elucidation of caryophyllane sesquiterpenoids from leaves of Eremophila spathulata

Crude extract of Eremophila spathulata leaves was investigated by semi-preparative scale high-performance liquid chromatography (HPLC), analytical scale HPLC, and hyphenated high-performance liquid chromatography-photodiode array-high-resolution mass spectrometry-nuclear magnetic resonance (HPLC-PDA-HRMS-SPE-NMR), which afforded seven previously unreported caryophyllane sesquiterpenoids. Semi-preparative scale separation of the crude extract afforded (1R*,4R*,9S*,E)-8-formyl-11,11-dimethylbicyclo[7.2.0]undec-7-ene-4-carboxylic acid (5) and analytical-scale HPLC separation afforded (1R*,4S*,7S*,9S*)-7-hydroxy-11,11-dimethyl-8-methylenebicyclo[7.2.0]undecane-4-carboxylic acid (1), (1S*,6R*,9R*,E)-10,10-dimethylbicyclo[7.2.0]undec-2-ene-2,6-dicarboxylic acid (2), (1R*,4S*,9S*)-11,11-dimethyl-8-oxobicyclo[7.2.0]undecane-4-carboxylic acid (3), and (1R*,4R*,9S*)-11,11-dimethyl-8-oxobicyclo[7.2.0]undecane-4-carboxylic acid (4). HPLC-PDA-HRMS-SPE-NMR afforded (1R*,4R*,9S*)-11,11-dimethyl-8-methylenebicyclo[7.2.0]undecane-4-carboxylic acid (6) and (1R*,4S*,9S*)-11,11-dimethyl-8-methylenebicyclo[7.2.0]undecane-4-carboxylic acid (7). The structures of all isolated compounds were established based on HRMS as well as extensive 1D and 2D NMR analysis. Relative configurations were determined by correlations in spectra from rotational Overhauser effect spectroscopy.