Catalytic asymmetric reactions for organic synthesis: the combined C-H activation/siloxy-cope rearrangement

Tetrakis(N-[4-dodecylbenzenesulfonyl]-(L)-prolinate) dirhodium [Rh(2)(S-DOSP)(4)]-catalyzed decomposition of vinyldiazoacetates in the presence of allyl silyl ethers results in the formation of the direct C-H insertion product and the product derived from a combined C-H activation/siloxy-Cope rearrangement. Both products are formed with very high diastereoselectivity (>94% de) and high enantioselectvity (78-93% ee). Under thermal or microwave conditions, the direct C-H insertion product undergoes a siloxy-Cope rearrangement in a stereoselective manner.     

Thermo-biolithography: a technique for patterning nucleic acids and proteins

We describe a "biolithographic" technique in which the unique properties of biopolymeric materials and the selective catalytic activities of enzymes are exploited for patterning surfaces under simple and bio-friendly conditions. We begin by coating a reactive film of the polysaccharide chitosan onto an inorganic surface (glass or silicon wafer). Chitosan's pH-responsive solubility facilitates film deposition, while the nucleophilic properties of this polysaccharide allow simple chemistries or biochemistries to be used to covalently attach species to the film. The thermally responsive protein gelatin is then cast on top of the chitosan film, and the gelatin gel serves as a sacrificial "thermoresist". Pattern transfer is accomplished by applying a heated stamp to melt specific regions of the gelatin thermoresist and selectively expose the underlying chitosan. Finally, molecules are conjugated to the exposed chitosan sublayer and the sacrificial gelatin layer is removed (either by treating with warm water or protease). To demonstrate the concept, we patterned a reactive dye (NHS-fluorescein), a model 20-base oligonucleotide (using standard glutaraldehyde coupling chemistries), and a model green fluorescent protein (using tyrosinase-initiated conjugation). Because gelatin can be applied and removed under mild conditions, sequential thermo-biolithographic steps can be performed without destroying previously patterned biomacromolecules. These studies represent the first step toward exploiting nature's exquisite specificity for lithographic patterning.     

Synthesis and evaluation of sphinganine analogues of KRN7000 and OCH

[structures: see text] The phytosphingosine-containing alpha-galactosylceramides (alpha-GalCers), KRN7000 and OCH, have been shown to activate NKT cells via interaction with CD1d, a member of the CD1 family of antigen presenting proteins. Evidence from KRN7000 stimulation of NKT cells suggests that alpha-GalCers may have applications in the treatment or prevention of a range of viral, bacterial, and autoimmune conditions. Moreover, OCH, a truncated analogue of KRN7000, appears to induce a T(H)2 bias, which could have implications for the treatment of autoimmune and inflammatory conditions. We have prepared the direct sphinganine-containing analogues of KRN7000 and OCH, 1 and 2, and found them to be comparable in activity to the parent compounds in inducing the release of IL-2, IL-4, and IFNgamma. In addition, compound 2 leads to a cytokine bias similar to that seen with OCH. This is significant because sphinganines are more easily accessed than phytosphingosines, which should facilitate SAR studies.     

Clean matrices and unit-regular matrices

An element in a ring R is said to be clean (respectively unit-regular) if it is the sum (respectively product) of an idempotent element and an invertible element. If all elements in R are unit-regular, it is known that all elements in R are clean. In this note, we show that a single unit-regular element in a ring need not be clean. More generally, a criterion is given for a matrix to be clean in a matrix ring M₂(K) over any commutative ring K. For K=Z, this criterion shows, for instance, that the unit-regular matrix is not clean. Also, this turns out to be the “smallest” such example.     

Homogenization approach to the multi-compartment model of perfusion

The paper deals with modelling of the coupled diffusion-deformation processes in biological tissues with potential applications in describing the blood perfusion, or fluid filtration phenomena in general. The micromodel to be homogenized is based on the Biot type model for the incompressible medium. Due to the strong heterogeneity in the permeability coefficients associated with three compartments of the representative microstructural cell (RMC), the homogenization of the model leads to the double diffusion phenomena. The resulting homogenized equations, involving the stress-equilibrium equation and other two equations governing the mass redistribution, describe the parallel diffusion in two high-conducting compartments (arterial and venous sectors) separated by the low conducting matrix which represents the perfused tissue. To obtain the homogenized model, the method of two scale convergence is applied. The homogenized coefficients are defined in terms of the characteristic response of the RMC. It is possible to identify the instantaneous and fading memory viscoelastic coefficients; other effective parameters, controlling the fluid redistribution between the compartments, are involved also in time convolutions. (© 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)     

Synthesis of Naturally Occurring Pyranonaphthoquinones: (±) 9-Demethoxyeleutherin, (±) 9-Demethoxyisoeleutherin,and Pentalongin via Nef Reaction

The article describes alternative method for the synthesis of (±) 9-demethoxyeleutherin and (±) 9-demethoxyisoeleutherin, the analogs of naturally occurring pyranonaphthoquinones antibiotics eleutherin and isoeleutherin. This methodology has provided the target molecules using a shorter route involving five simple chemical transformations with Nef reaction as a key step. All the intermediates and target molecules were completely characterized by spectral techniques and confirmed by comparison with literature data. Further we have extended Nef protocol toward formal synthesis of naturally occuring pyranonaphthoquinone pentalongin. We accomplished synthesis of of 2-(1,4-dimethoxynaphthalen-2-yl)acetic acid devoid of very toxic cyanide intermediates, which has been converted into pentalongin.     

Chemoenzymatic asymmetric synthesis of fluoxetine,atomoxetine, nisoxetine,and duloxetine

The asymmetric synthesis of two well-known anti-depressant drugs, fluoxetine and duloxetine has been accomplished in a chemoenzymatic manner. The main highlight of the synthesis is the enantioselective cyanohydrin formation by a plant (R)-HNL (hydroxynitrile lyase). The enantiopure cyanohydrins are then synthetically manipulated into the above two drug molecules and two of their structural analogues, atomoxetine and nisoxetine.     

Semi‐synthesis and NMR spectral assignments of flavonoid and chalcone derivatives

Previous investigations of the aerial parts of the Australian plant Eremophila microtheca and Syzygium tierneyanum resulted in the isolation of the antimicrobial flavonoid jaceosidin ( 4 ) and 2′,6′‐dihydroxy‐4′‐methoxy‐3′,5′‐dimethyl chalcone ( 7 ), respectively. In this current study, compounds 4 and 7 were derivatized by acetylation, pivaloylation, and methylation reactions. The final products, 5,7,4′‐triacetoxy jaceosidin ( 10 ), 5,7,4′‐tripivaloyloxy jaceosidin ( 11 ), 5,7,4′‐trimethoxy jaceosidin ( 12 ), 2′,6′‐diacetoxy‐4′‐methoxy‐3′,5′‐dimethyl chalcone ( 13 ), 2′‐hydroxy‐4′‐methoxy‐6′‐pivaloyloxy‐3′,5′‐dimethyl chalcone ( 14 ), and 2′‐hydroxy‐4′,6′‐dimethoxy‐3′,5′‐dimethyl chalcone ( 15 ) were all fully characterized by NMR and MS. Derivatives 10 and 13 have been previously reported but were only partially characterized. This is the first reported synthesis of 11 and 14 . The natural products and their derivatives were evaluated for their antibacterial and antifungal properties, and the natural product, jaceosidin ( 4 ) and the acetylated derivative, 5,7,4′‐triacetoxy jaceosidin ( 10 ), showed modest antibacterial activity (32–128 µg/ml) against Staphylococcus aureus strains. Copyright © 2016 John Wiley & Sons, Ltd.