New Sesterterpenes from Marine Sponges from the Tropical Waters of the Kingdom of Tonga

<p>Over the course of this study, various species of Tongan marine sponges were investigated using an NMR-based screening method and has resulted in the discovery of three new sesterterpenes and 11 known compounds. Examination of the sponge Fascaplysinopsis sp. resulted in the isolation of two novel sesterterpenes, isoluffariellolide (46) and 1-O-methylisoluffariellolide (47). Compounds 46 and 47 share the same backbone pattern as the known luffariellolide (45) and 25-Omethylluffariellolide (107) respectively, and differ only in the substitution pattern of the butenolide rings. Isoluffariellolide (46) was found to be approximately six times less cytotoxic than 1-O-methylisoluffariellolide (47). Interestingly, these results suggested that the 1-O-methyl group in compound 47 plays an important role in the cytotoxicity of the compound. Secothorectolide (49), a new ring-opened and geometric isomer of the known compound thorectolide (48), was obtained from a sponge of the order Dictyoceratida. This ring closure and opening relationship was also observed between manoalide (109) and secomanoalide (110), as well as luffariellins A (141) and B (142). Despite the different carbon skeleton, the functional groups in 141 and 142 are similar with those in 109 and 110, respectively, and not surprisingly the biological properties are almost identical. The biological activities of compounds 48 and 49 were almost the same, which would give an insight into the structure-activity relationship (SAR) between these types of compounds.</p>

New Sesterterpenes from Marine Sponges from the Tropical Waters of the Kingdom of Tonga

<p>Over the course of this study, various species of Tongan marine sponges were investigated using an NMR-based screening method and has resulted in the discovery of three new sesterterpenes and 11 known compounds. Examination of the sponge Fascaplysinopsis sp. resulted in the isolation of two novel sesterterpenes, isoluffariellolide (46) and 1-O-methylisoluffariellolide (47). Compounds 46 and 47 share the same backbone pattern as the known luffariellolide (45) and 25-Omethylluffariellolide (107) respectively, and differ only in the substitution pattern of the butenolide rings. Isoluffariellolide (46) was found to be approximately six times less cytotoxic than 1-O-methylisoluffariellolide (47). Interestingly, these results suggested that the 1-O-methyl group in compound 47 plays an important role in the cytotoxicity of the compound. Secothorectolide (49), a new ring-opened and geometric isomer of the known compound thorectolide (48), was obtained from a sponge of the order Dictyoceratida. This ring closure and opening relationship was also observed between manoalide (109) and secomanoalide (110), as well as luffariellins A (141) and B (142). Despite the different carbon skeleton, the functional groups in 141 and 142 are similar with those in 109 and 110, respectively, and not surprisingly the biological properties are almost identical. The biological activities of compounds 48 and 49 were almost the same, which would give an insight into the structure-activity relationship (SAR) between these types of compounds.</p>

Photopharmacology of Azo-Combretastatin-A4: Tubulin Polymerization Inhibitors utilizing Green Chemistry Key Step

: Tubulin polymerization inhibitors (TPIs) are promising ligands utilized in chemotherapy for modern cancer treatment. However, the current TPIs exhibit many serious side effects that may pose limitations in chemotherapy. Combretastatin A-4 (CA-4) is a natural TPI that binds at the colchicine binding site located on microtubules. The only cis isomer of CA-4 is bio-active; however, due to its short half-life, it isomerizes quickly to its bio-inactive trans geometric isomer. Preventing shortcomings of CA-4, azobenzene based CA-4, called azo-CA-4 (azo-CA-4), identified as a novel TPI. The geometric isomerization of azo-CA-4 can be controlled upon exposure of ultraviolet (UV) light to remotely control its bioactivity. Cis-azo-CA-4 is 200-500 times more active (IC50 = 0.2-10 µM) than trans-azo-CA-4 (IC50 = 50-110 µM) against various cancer cell lines. Photo-pharmacology uses light to control drug activity, introduce a unique mechanism to develop novel photo-responsive TPIs. Further, the green chemistry approach using ethanol and water as a green solvent in the synthesis of azo-CA-4 delivers advanced methodology in novel TPI development .

Direct observation of the geometric isomer selectivity of a reaction controlled via adsorbed bromine

Methods to improve the specificity of stereoselective reactions are paramount to the viability of reaction-based processes.

Terphenyl backbone-based donor–π–acceptor dyads: geometric isomer effects on intramolecular charge transfer

The molecular geometry effects of ortho, meta, and para-terphenyl based donor–π–acceptor (D–π–A) dyads on intramolecular charge transfer (ICT) were studied to investigate structure-ICT relationships.

Stereospecific Synthesis of Multi-Aryl Substituted Olefins and 1,3-Dienes via 1,4-Palladium Migration/Suzuki Coupling Sequence

Multi-aryl substituted olefins and 1,3-dienes are important structural motifs in material molecules, and the stereochemistry of these structures exerts significant influence on the material properties. At present, the lack of effective methods to control the geometry of the double bonds has been a hurdle for the discovery of advanced material. We report herein the development of a 1,4-palladium migration/Suzuki coupling sequence for the efficient synthesis of these interesting molecules. A precise reactivity balance of the used organoboronates played a vital role in this process. The practicality of this method was demonstrated by the excellent capability and flexibility in stereochemical control, broad substrate scope, excellent functional group tolerance, as well as versatile conversion with obtained products and easy scalability. Furthermore, the power of this method is also highlighted by the aggregation-induced emission (AIE) feature studies of some obtained products, especially the easy accessibility of several geometric isomer pairs with a marked difference on photolumnescent quantum yield values.

Stereospecific Synthesis of Multi-Aryl Substituted Olefins and 1,3-Dienes via 1,4-Palladium Migration/Suzuki Coupling Sequence

Multi-aryl substituted olefins and 1,3-dienes are important structural motifs in material molecules, and the stereochemistry of these structures exerts significant influence on the material properties. At present, the lack of effective methods to control the geometry of the double bonds has been a hurdle for the discovery of advanced material. We report herein the development of a 1,4-palladium migration/Suzuki coupling sequence for the efficient synthesis of these interesting molecules. A precise reactivity balance of the used organoboronates played a vital role in this process. The practicality of this method was demonstrated by the excellent capability and flexibility in stereochemical control, broad substrate scope, excellent functional group tolerance, as well as versatile conversion with obtained products and easy scalability. Furthermore, the power of this method is also highlighted by the aggregation-induced emission (AIE) feature studies of some obtained products, especially the easy accessibility of several geometric isomer pairs with a marked difference on photolumnescent quantum yield values.

Development and Characterization of Monoclonal Antibodies for the Mycotoxin Citreoviridin

Citreoviridin (CTV) in an inhibitor of mitochondrial ATPase that has been isolated from molded yellow rice and linked to the human disease Shoshin-kakke (acute cardiac beriberi). The disease results from a deficiency of thiamine, however, purified CTV can reproduce the symptoms in experimental animals. The link between CTV and Shoshin-kakke has been difficult to resolve, in part because cases of the disease are rare. In addition to rice, CTV has been found in maize, pecan nuts, and wheat products. A method to screen for CTV and its geometric isomer, iso-CTV, in commodities was developed, based upon the isolation of two novel monoclonal antibodies (mAb). In an antigen-immobilized competitive enzyme-linked immunosorbent assay format (CI-ELISA), the observed IC50s for CTV were 11 ng/mL and 18 ng/mL (mAbs 2-2 and 2-4, respectively). The assays were relatively tolerant to methanol and acetonitrile, which allowed their application to the detection of CTV in spiked polished white rice. For quantification, a standard mixture of CTV and iso-CTV was used, along with matrix matched calibration. The dynamic range of the ELISA using mAb 2-4 was equivalent to 0.23 to 2.22 mg/kg in rice. Recoveries over the range of 0.36 to 7.23 mg/kg averaged 97 ± 10%. The results suggest that the mAb 2-4-based immunoassay can be applied to the screening of white rice for CTV. Both mAbs were also observed to significantly enhance the fluorescence of the toxin.

THEORETICAL STUDY OF STRUCTURAL GEOMETRY AND ELECTRONIC PROPERTIES OF MAGNESIUM DIBORETH (MgB2)

The present work made a molecular theoretical study of the structural and electronic properties of the geometric isomers of magnesium diboride (MgB2). The systems have specific characteristics and are very promising for technological applications, such as magnetic resonance imaging devices, motors, and generators. The same is still used in the industries of electronic devices, floating trains (MAGLEV), electricity and Biomagnetism. The results show that the geometric isomer with the lowest energy value is the cyclic species, which is the most stable. The formation enthalpies found were 205.38 Kcal mol-1 and 45.66 Kcal mol-1 for MgB2-cyclic and for B-Mg-B respectively. By means of the analysis Frontier Molecular Orbital it was possible to identify the shape of the HOMO - LUMO orbitals and how they contribute to the ligand and anti-ligand bands and thus to the superconducting properties of the compound. Finally, the NBO analysis confirmed that the most stable geometric isomer is MgB2-cyclic, presenting more interactions between donor or receptor orbitals.