Dihydroisocoumarin derivatives with antifouling activities from a gorgonian-derived Eurotium sp. fungus

Five pairs of new dihydroisocoumarin enantiomers, (±)-eurotiumides A–E, and two related racemates, (±)-eurotiumides F and G, were isolated from a gorgonian-derived fungus, Eurotium sp. XS-200900E6. The enantiomeric separations for (±)-eurotiumides A–E were achieved by chiral-HPLC, and their absolute configurations were determined by ECD spectra. All of the isolated compounds are rare dihydroisocoumarin derivatives with a methoxy at C-4. (+)- And (−)-eurotiumides B and D with cis configurations of H-3/H-4 exhibited potent antifouling activities against the larval settlement of the barnacle Balanus amphitrite with the EC₅₀ values ranging from 0.7 to 2.3 μg/mL, and displayed high therapeutic ratios (LC₅₀/EC₅₀ >15). The tested compounds also showed extensive antibacterial activities. It was the first report of antifouling activities for dihydroisocoumarin derivatives.     

Dihydroisocoumarins and Dihydroisoflavones from the Rhizomes of Dioscorea collettii with Cytotoxic Activity and Structural Revision of 2,2′-Oxybis(1,4-di-tert-butylbenzene)

The investigation of the constituents of the rhizomes of Dioscorea collettii afforded one new dihydroisocoumarin, named (−)-montroumarin (1a), along with five known compounds—montroumarin (1b), 1,1′-oxybis(2,4-di-tert-butylbenzene) (2), (3R)-3′-O-methylviolanone (3a), (3S)-3′-O-methylviolanone (3b), and (RS)-sativanone (4). Their structures were elucidated using extensive spectroscopic methods. To the best of our knowledge, compound 1a is a new enantiomer of compound 1b. The NMR data of compound 2 had been reported but its structure was erroneous. The structure of compound 2 was revised on the basis of a reinterpretation of its NMR data (1D and 2D) and the assignment of the ¹H and ¹³C NMR data was given rightly for the first time. Compounds 3a–4, three dihydroisoflavones, were reported from the Dioscoreaceae family for the first time. The cytotoxic activities of all the compounds were tested against the NCI-H460 cell line. Two dihydroisocoumarins, compounds 1a and 1b, displayed moderate cytotoxic activities, while the other compounds showed no cytotoxicity.     

Polyhydroxylated macrolide isolated from the endophytic fungus Pestalotiopsis mangiferae

A new polyhydroxylated macrolide, named mangiferaelactone (1) was isolated from a solid culture of the endophytic fungus Pestalotiopsis manguiferae, together with ten known compounds [(6S,1′S)-LL-P880α; (6S,1′S,2′R)-LL-P880β; (1′S,2′R)-LL-880γ; (1′R)-dehydropestalotin; (−)-5-carboxylmellein; (−)-5-methylmellein; (−)-5-hydroxylmethylmellein; arabenoic acid; 5,6-dihydro-4-methoxy-2H-pyran-2-one; and the (−)-2-hexylidene-3-methylsuccinic acid]. P. manguiferae was isolated from Hyptis dilatata, a small shrub common in the central region of Panama. The structure of compound 1 was elucidated by a combination of spectroscopic methods (IR, MS, optical rotation, 1D and 2D NMR spectroscopy). The absolute configuration of 1 was established as 4R,7R,8R,9S by application of vibrational circular dichroism (VCD). Compound 1 showed a minimum inhibitory concentration (MIC) of 1.6863 mg/mL against Listeria monocytogenes, and 0.5529 mg/mL against Bacillus cereus. No activity was observed for compound 1 against Plasmodium falciparum or Trypanosoma cruzi; likewise, no cytotoxic activity was observed against A2058 and H522-T1 cells.     

Cytotoxic cembranoids from the Red Sea soft coral, Sarcophyton auritum

Chemical investigation of the Red Sea soft coral Sarcophyton auritum led to the isolation and structure elucidation of two new diterpene cembranoids; 2-epi-sarcophine (2) and (1R,2E,4S,6E,8R,11R,12R)-2,6-cembradiene-4,8,11,12-tetrol (4), as well as two known diterpene cembranoids, reported for the first time from this species, namely sarcophine (1) and (+)-7α,8β-dihydroxydeepoxysarcophine (3). Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The isolated cembranoids were found to display high cytotoxicity against HepG2 (liver cancer cell line) and MCF-7 (breast cancer cell line).     

Synthesis of (S)-2-amino-7-methoxytetralin and isoindolo[1,2-a]isoquinolinone derivatives from l-aspartic acid

This paper describes a new total synthesis for (S)-2-amino-7-methoxytetralin, (S)-7-MeO-AT, from l-aspartic acid in an overall yield of 10% over nine steps. The major loss was ascribed to a key intramolecular Friedel–Crafts cyclization step, which afforded up to 36% yield. Attempts to perform a Friedel–Crafts cyclization of an intermediate phthalimide protected amino alcohol 13 did not give the desired protected (S)-7-MeO-AT. On the other hand, two new isoindolo[1,2-a]isoquinolinone derivatives 14 and 15, were isolated in 21 and 11% yield, respectively. The yield of 15 was improved to 70%.     

Microwave-assisted synthesis and reversed-phase high-performance liquid chromatographic separation of diastereomers of (R,S)-baclofen using ten chiral derivatizing reagents designed from trichloro-s-triazine

Four dichloro-s-triazine (DCT) and five monochloro-s-triazine (MCT) chiral derivatizing reagents (CDRs) were synthesized by incorporating amino acid amide moieties as chiral auxiliaries in trichloro-s-triazine and its 6-methoxy derivative, respectively. Another MCT reagent was synthesized by substitution of two chlorine atoms with two different amino acid amides in trichloro-s-triazine. These reagents were used for synthesis of diastereomers of (R,S)-baclofen under microwave irradiation (i.e. 60 s at 85% power using DCT reagents and 90 s at 85% power using MCT reagents). The diastereomers were separated on a reversed-phase C18 column using mixtures of methanol with aqueous trifluoroacetic acid (TFA) with UV detection at 230 nm. The separation behavior in terms of retention times and resolutions obtained for the two sets of diastereomers prepared with DCT and MCT reagents were compared among themselves and among the two groups. Longer retention times and better resolutions were observed with DCT reagents as compared to MCT reagents. The calibration curves were linear for both (R)- and (S)-baclofen in the concentration range 50-500 μg/ml. The average regression was 0.999 for both (R)- and (S)-baclofen. The RSD for (R)-baclofen was 0.40-0.86% for intra-day precision and 0.60-1.40% for inter-day precision and these values for (S)-baclofen were 0.52-0.75% and 0.64-1.32%, respectively. The recovery was 97.2-98.9% for (R)- and 97.0-98.9% for (S)-baclofen. The limit of detection was 1.63ng/ml and 1.52ng/ml for (R)- and (S)-baclofen, respectively.     

Novel octulosonic acid derivatives in the composite Smallanthus sonchifolius

Two novel octulosonic acid derivatives with a 6,8-dioxabicyclo[3.2.1]octane skeleton that are major water-soluble phenolic compounds were found in the roots of Smallanthus sonchifolius. The structures of these compounds were determined to be (1R,2S,3S,4R,5S,7R)-4-hydroxy-7-hydroxymethyl-3-[3-(3,4-dihydroxyphenyl)-1-oxo-2-propenyloxy]-6,8-dioxabicyclo[3.2.1]octan-5-carboxylic acid (4-O-caffeoyl-2,7-anhydro-d-glycero-β-d-galacto-oct-2-ulopyranosonic acid) and (1R,2S,3R,4R,5S,7R)-2,4-dihydroxy-7-hydroxymethyl-2,3-bis[3-(3,4-dihydroxyphenyl)-1-oxo-2-propenyloxy]-6,8-dioxabicyclo[3.2.1]octan-5-carboxylic acid (4,5-di-O-caffeoyl-2,7-anhydro-d-glycero-β-d-galacto-oct-2-ulopyranosonic acid) by MS, NMR and CD spectral analyses.     

Stereochemical challenges in characterizing nitrogenous spiro-axane sesquiterpenes from the Indo-Pacific sponges Amorphinopsis and Axinyssa

An investigation was conducted to identify the structures and bioactive properties of five compounds isolated from the Halichondrida sponges Amorphinopsis foetida and Axinyssa aplysinoides. All compounds possessed the spiro-axane sesquiterpene core and all were substituted at C-2 with nitrogen containing functionality. The stereochemistry of one known compound has been revised to (2R,5R,10S)-2-formamido-6-axene (3). It exhibited mild selective solid tumor and mild antibacterial activity and was found from Axinyssa. A second known substance whose stereochemistry has also been revised, (2R,5R,10S)-2-isothiocyanato-6-axene (4) plus its undescribed diastereomer (5) were isolated from Amorphinopsis. Both sponges were the source of two new N-phenethyl-2-formamido-6-axene diastereomeric compounds 6 and 7. No solid tumor or antibacterial activity was found for 4-7.     

Two New Compounds Isolated from<em> Liriope muscari</em>

Two new compounds, (2S,3R)-methyl 7-hydroxy-2-(4-hydroxy-3-methoxy-phenyl)-3-(hydroxymethyl)-2,3-dihydrobenzofuran-5-carboxylate (1) and (4R,5S)-5-(3-hydroxy-2,6-dimethylphenyl)-4-isopropyldihydrofuran-2-one (2), tentatively named norcurlignan and limlactone, respectively, were isolated from Liriope muscari, together with the known compound (-)-pinoresinol (3). The structures of these compounds were elucidated and characterized on the basis of 1D NMR, 2D NMR, CD and MS data. The in vitro antioxidant activities of compounds 1-3 were assessed by the DPPH and ABTS scavenging methods.     

Total synthesis of the aromatase inhibitor dihydroisocoumarin via protective opening of lactones

Asymmetric total synthesis of a dihydroisocoumarin, (3R,4R)-(−)-6-methoxy-1-oxo-3-pentyl-3,4-dihydro-1H-isochromen-4-yl acetate (1) starting from commercially available m-anisic acid is described. Herein, we depict the use of protective opening of lactones and construction of δ lactone. The synthesis involves Wittig, Grubbs cross metathesis, and Sharpless dihydroxylation reactions.     

A xanthone and a polyketide derivative from the leaves of Cassia obtusifolia (Leguminosae)

A new xanthone, 1,8-dihydroxy-3-methoxy-6-methylxantone and a new polyketide derivative, (4R^∗,5S^∗,6E,8Z)-ethyl-4-((E)-but-1-enyl)-5-hydroxypentdeca-6,8-dienoate, together with 20 known secondary metabolites, including 2 steroids, 4 xanthones, 10 anthraquinones, 2 triterpenoids, 1 fatty ester, and (E)-eicos-14-enoic acid, were isolated from the leaves of Cassia obtusifolia. To the best of our knowledge, the last compound was isolated from a natural source for the first time. The structures of all the compounds were elucidated on the basis of 1D and 2D NMR experiments. Some of the compounds were tested against Salmonella typhi, Staphylococcus aureus, Candida albicans ATCC 9002, and Candida tropicalis, they did not show any activity.     

Microwave-assisted synthesis of methyl (1S,2R,4S,5S)-7-aza-5-hydroxybicyclo[2.2.1]heptane-2-carboxylate through unexpected stereoselective substitution reaction

Methyl (1S,2R,4S,5R)-7-aza-5-bromo-bicyclo[2.2.1]heptane-2-carboxylate was synthesized in high yield in short time from methyl (1R,2S,4R,5R)-2-amino-4,5-dibromocyclohexanecarboxylate through intramolecular cycloamination under microwave-assisted conditions. The following substitution reaction by trifluoro-acetate anion also took place in microwave-assisted conditions to afford methyl (1S,2R,4S,5S)-7-aza-5-hydroxy-bicyclo[2.2.1]heptane-2-carboxylate. In the acyloxylation reaction, unusual endo-selectivity was observed owing to 7-azabicyclo[2.2.1]heptane skeleton.     

Diarylnonanoids and their glucosides from Erica cinerea

The reinvestigation of Erica cinerea fresh aerial parts led to the isolation of two new diarylnonanoid aglycones along with their glucosides. From spectroscopic data, their structures were elucidated as rel-(3R,7R)-1,9-bis(p-hydroxyphenyl)-3,7-dihydroxynonan-5-one named ericanone, ericanone 3-β-d-glucoside, (3S)-3,7-anhydro-6,7-dehydroericanone and (3S)-3,7-anhydro-6,7-dehydroericanone 4′-β-d-glucoside. Contrary to the numerous diarylheptanoids more frequently distributed in the plant kingdom, the rare diarylnonanoids were previously restricted to the genus Myristica of the Myristicaceae plant family.     

Stereochemical revision of communiols D and H through synthesis

Based on the previously revised stereochemistries for communiols A-C, the ent-8-epi- and ent-6-epi-stereoisomers of the original structures proposed for communiols D and H, respectively, were synthesized as highly probable candidates for their genuine structures by using the Sharpless asymmetric dihydroxylation as the source of chirality. Complete accord in spectral properties between each synthetic candidate and the corresponding natural material as well as the fact that communiols A-D and H were all isolated from the same fungal source, led us to the conclusion that the stereochemistries of communiols D and H should also be revised to their (3S,5S,7R,8S,11R)- and (5S,7R,8S)-forms, respectively.     

Cascade transformation of 4-hydroxymethyl-2-carene into novel cage methanopyrano[4,3-b]thieno[3,2-g]benzofuran derivative

Reaction of trans-4-hydroxymethyl-2-carene with thiophene- 2-carbaldehyde under heterogeneous catalysis by K10 clay affordsubstitutedmethanopyrano[4,3-b]thieno[3,2-g]- benzofuran, a complex 5-membered chiral cage heterocyclic compound containing two thiophene moieties. Its structure was determined by 1D and 2D NMR experiments (HSQC, HMBC, COSY, NOESY) and HRMS.     

Isolation, characterisation and synthesis of an insecticidal tetramethyltetrahydrochromenedione-spiro-bicyclo[3.1.1]cycloheptane from two species of Myrtaceae

A new moderately insecticidal compound, named ficifolidione, has been isolated from the hexane extract of the aerial parts of two species of Myrtaceae, Eucalyptus ficifolia and Kunzea ericoides. Its structure, (1′R,2′R,4R)-4-isobutyl- 6,6,8,8-tetramethyl-2,3,4,8-tetrahydrochromene-5,7-dione-2-spiro-2′-6,6-dimethyl-bicyclo[3.1.1]heptane (1), was confirmed by synthesis from syncarpic acid, isovaleraldehyde and (1S)-β-pinene.     

Synthesis and photochromism of a series of new 2-unsubstituted 3-(2-benzylbenzoyl)quinolin-4(1H)-ones

Synthesis and characterization of a series of new 2-unsubstituted 3-(2-benzylbenzoyl)quinolin-4(1H)-ones is described. In addition to their potential biological activity, these compounds exhibit photoreversible photochromic properties in anaerobic conditions. Using the 1 and 2D NMR techniques we demonstrated that the coloration occurred owing to the formation of fluorescent 5a,6-dihydrobenzo[b]acridin-(5H)-ones. The photoreaction is stereoselective and the S,R-isomers are the major products (83%) whereas the S,S-isomers are the minor (6%). In addition, the irreversible formation of two oxidation products, 3-(2-benzoylbenzoyl)quinolin-4(1H)-ones, and acridin-12(5H)-one derivatives was observed in the presence of air.     

Gomadalactones A, B, and C: novel 3-oxabicyclo[3.3.0]octane compounds in the contact sex pheromone of the white-spotted longicorn beetle, Anoplophora malasiaca

The ether extract of the females of white-spotted longicorn beetle Anoplophora malasiaca showed activity as contact sex pheromone to males. The extract was fractionated, and a pheromonal activity was revealed only when three fractions; n-hexane, n-hexane/EtOAc 9:1, and EtOAc were blended. The relative structures of gomadalactone A, B, and C, three active components isolated from the EtOAc fraction, were determined by spectroscopic studies to be (1S^∗,4R^∗,5S^∗)-5-hydroxy-4-[(E)-7-hydroxy-4-methylhept-3-enyl]-4,8-dimethyl-3-oxabicyclo[3.3.0]octan-7-en-2,6-dione, (1R^∗,4R^∗,5R^∗)-5-hydroxy-4-[(E)-7-hydroxy-4-methylhept-3-enyl]-4,8-dimethyl-3-oxabicyclo[3.3.0]octan-7-en-2,6-dione, and (1S^∗,4R^∗,5S^∗,8S^∗)-5-hydroxy-4-[(E)-7-hydroxy-4-methylhept-3-enyl]-4,8-dimethyl-3-oxabicyclo[3.3.0]octan-2,6-dione, respectively.     

Synthesis of 2,3,4-trideoxy-4-c-(phenylphosphinyl)-dl-glycero-pentofuranose and its 1,5-diacetate

Synthesis of 2,3,4-trideoxy-4-C-(phenylphosphinyl)-dl-glycero-pentofuranose (11) starting from 2-furanmethanol was successful. The reaction of methyl 2,3-dideoxy-(1S)-dl-pentopyranosid-4-ulose 4-(p-toluenesulfonylhydrazone) with methyl phenylphosphonite gave methyl (4RS)-2,3,4-trideoxy-4-C-[(methoxy)phenylphosphinyl]-4-C-(p-toluenesulfonylhydrazino)-(1S)-dl-pentopyranoside (7), which on treatment with sodium borohydride afforded methyl 2,3,4-trideoxy-4-C-[(methoxy)phenylphosphinyl]-(1S)-dl-glycero-pentopyranoside (9). Treatment of compound 9 with SDMA followed by hydrolysis and treatment with acetic anhydride-pyridine afforded 1,5-diacetate 12 of compound 11.     

Biomimetically inspired total synthesis of (12S)-12-hydroxymonocerin and (12R)-12-hydroxymonocerin

A concise asymmetric total synthesis of (12S)-12-hydroxymonocerin (1) and (12R)-12-hydroxymonocerin (2) were efficiently achieved from the known 4-bromo-2,6-dimethoxyphenol. The synthetic approach was inspired by our biomimetic synthesis of (+)-monocerin (3) and 7-O-demethylmonocerin (4). The cis-fused furobenzopyranones of 1 and 2 was efficiently constructed via an intramolecular nucleophilic trapping of a quinonemethide intermediate, which was obtained by benzylic oxidation of compound 10 using 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ).