The total synthesis of gambierol

This communication describes the total synthesis of the marine polyether toxin, gambierol. This work couples our iterative C-glycoside/enol ether-olefin metathesis strategy to the subunits with a unique olefin metathesis/carbonyl olefination reaction to bring the subunits together.     

A study toward understanding the role of a phosphorus stereogenic center in (5S)-1,3-diaza-2-phospha-2-oxo-3-phenylbicyclo(3.3.0)octane derivatives as catalysts in the borane-mediated asymmetric reduction of prochiral ketones

Representative diastereomeric pairs of chiral catalysts, containing the (5S)-1,3-diaza-2-phospha-2-oxo-3-phenylbicyclo(3.3.0)octane moiety, with different stereochemistry at the phosphorus stereogenic center, have been synthesized and their stereoselection in the borane-mediated asymmetric reduction of representative prochiral ketones has been described.     

Wittig and Wittig-Horner reactions under phase transfer catalysis conditions

Wittig and Wittig-Horner reactions are favorite tools in preparative organic chemistry. These olefination methods enjoy widespread and recognition because of their simplicity, convenience, and effciency. Phase transfer catalysis (PTC) is a very important method in synthetic organic chemistry having many advantages over conventional, homogenous reaction procedures. In this paper, we attempt to summarize the aspects concerning Wittig and Wittig-Horner reactions that take place under phase transfer catalysis conditions.     

Isolation and characterization of a novel lepidopteran-selective toxin from the venom of South Indian red scorpion, Mesobuthus tamulus

Background

Scorpion venom contains insect and mammal selective toxins. We investigated the venom of the South Indian red scorpion, Mesobuthus tamulus for the purpose of identifying potent insecticidal peptide toxins.

Results

A lepidopteran-selective toxin (Buthus tamulus insect toxin; ButaIT) has been isolated from this venom. The primary structure analysis reveals that it is a single polypeptide composed of 37 amino acids cross-linked by four disulfide bridges with high sequence homology to other short toxins such as Peptide I, neurotoxin P2, Lqh-8/6, chlorotoxin, insectotoxin I5A, insect toxin 15 and insectotoxin I1. Three dimensional modeling using Swiss automated protein modeling server reveals that this toxin contains a short α-helix and three antiparallel β-strands, similar to other short scorpion toxins. This toxin is selectively active on Heliothis virescens causing flaccid paralysis but was non-toxic to blowfly larvae and mice.

Conclusion

This is the first report of a Heliothine selective peptide toxin. Identification of diverse insect selective toxins offer advantages in employing these peptides selectively for pest control.     

Long-term effects of human induced pluripotent stem cell-derived retinal cell transplantation in Pde6b knockout rats

Retinal degenerative disorders, including age-related macular degeneration and retinitis pigmentosa (RP), are characterized by the irreversible loss of photoreceptor cells and retinal pigment epithelial (RPE) cells; however, the long-term effect of implanting both human induced pluripotent stem cell (hiPSC)-derived RPE and photoreceptor for retinal regeneration has not yet been investigated. In this study, we evaluated the long-term effects of hiPSC-derived RPE and photoreceptor cell transplantation in Pde6b knockout rats to study RP; cells were injected into the subretinal space of the right eyes of rats before the appearance of signs of retinal degeneration at 2–3 weeks of age. Ten months after transplantation, we evaluated the cells using fundus photography, optical coherence tomography, and histological evaluation, and no abnormal cell proliferation was observed. A relatively large number of transplanted cells persisted during the first 4 months; subsequently, the number of these cells decreased gradually. Notably, immunohistochemical analysis revealed that the hiPSC-derived retinal cells showed characteristics of both RPE cells and photoreceptors of human origin after transplantation. Functional analysis of vision by scotopic electroretinogram revealed significant preservation of vision after transplantation. Our study suggests that the transplantation of hiPSC-derived retinal cells, including RPE cells and photoreceptors, has a potential therapeutic effect against irreversible retinal degenerative diseases.Subject terms: Translational research, Stem-cell research, Retina     

First principle study of adsorption of boron-halogenated system on pristine graphyne

To ensure the possibility of using graphyne as a gas sensor, we have studied the adsorption of boron-halogenated system on pristine graphyne with the help of density functional theory using generalized gradient approximation. Depending on binding energy the most stable orientation, adsorption strength and optimal distance between the above mention molecules and graphyne surface have been determined. The band gap of graphyne slightly increases with the adsorption of the boron-halogenated system. The graphyne system behaves as n-type semiconductor when it interacts with BI₃ and BCl₃ molecules, and it behaves as p-type semiconductor when interaction with BF₃ molecule takes place. Our result reveals that the electronic properties of pristine graphyne are highly influenced by the adsorption of boron-halogenated molecule. We have observed that pristine graphyne has zero electric dipole moment, but with the interaction of boron-halogenated molecule, a significant change in the electric dipole moment takes place. Hence, by measuring the electric dipole moment change, graphyne-based gas sensor can be design for the detection of above-mentioned molecules.     

Development and validation of HPLC method for the resolution of drug intermediates: DL-3-Phenyllactic acid, DL-O-acetyl-3-phenyllactic acid and (+/-)-mexiletine acetamide enantiomers

Sensitive and specific, high-performance liquid chromatography (HPLC) methods have been developed and validated for linearity, accuracy and precision for the quantification of dl-3-phenyllactic acid, dl-O-acetyl-3-phenyllactic acid and (+/-)-mexiletine acetamide enantiomers. Chromatographic separations were performed on a Chiralcel OJ-H column (0.46 mm x 250 mm, 5 microm, Daicel Chemical Industries, Japan) based on cellulose tris-(4-methyl benzoate) chiral stationary phase. The mobile phase consists of hexane and isopropanol (IPA) in the ratio of 90:10 containing 0.1% trifluoroacetic acid (in case of dl-3-phenyllactic acid and dl-O-acetyl-3-phenyllactic acid) and hexane and IPA (95:5) containing 0.1% triethylamine (in case of (+/-)-mexiletine acetamide) and the flow rate was set at 0.5 ml/min at 25 degrees C. The detection was carried out at 261 nm for dl-3-phenyllactic acid and dl-O-acetyl-3-phenyllactic acid and at 254 nm for (+/-)-mexiletine acetamide. The developed methods were utilized for monitoring the progress of lipase catalyzed enantioselective synthesis of O-acetyl-3-phenyllactic acid and mexiletine acetamide from dl-3-phenyllactic acid and (+/-)-mexiletine, respectively.     

LEP constraints on grand unified theories

Recent developments on grand unified theories (GUTs) in the context of the LEP measurements of the coupling constants will be reviewed. The three coupling constants at the electroweak scale have been measured at LEP quite precisely. One can allow these couplings to evolve with energy following the renormalization group equations for the various groups and find out whether all the coupling constants meet at any energy. It was pointed out that the minimalSU (5) grand unified theory fails to satisfy this test. However, various extensions of the theory are still allowed. These extensions include (i) supersymmetricSU (5) GUT, with some arbitrariness in the susy breaking scale arising from the threshold corrections, (ii) non-susySU (5) GUTs with additional fermions as well as Higgs multiplets, which has masses of the order of TeV, and (iii) non-renormalizable effect of gravity with a fine tuned relation among the coupling constants at the unification energy. The LEP results also constrain GUTs with an intermediate symmetry breaking scale. By adjusting the intermediate symmetry breaking scale, one usually can have unification, but these theories get constrained. For example, the left-right symmetric theories coming from GUTs can be broken only at energies higher than about ～ 10¹⁰ GeV. This implies that if right handed gauge bosons are found at energies lower than this scale, then that will rule out the possibility of grand unification. Another recent interesting development on the subject, namely, low energy unification, will be discussed in this context. All the coupling constants are unified at energies of the order of ～ 10⁸ GeV when they are embedded in anSU (15) GUT, with some particular symmetry breaking pattern. But even in this case the results of the intermediate symmetry breaking scale remain unchanged.     

Synthesis of multi-functional alkenes via Wittig reaction with a new-type of phosphorus ylides

A Bu₃P-mediated mild and efficient synthesis of multi-functional alkenes has been described starting from substituted acrylate with aldehydes. In situ generated zwitterionic intermediates underwent proton-exchange to afford ylide intermediates, which were trapped by corresponding aldehydes providing the products in up to 92% yield with complete E-stereoselectivity. Further derivatization of the products was performed to furnish functional pyridazinones.