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Diversity-oriented synthesis of drug-like macrocyclic scaffolds using an orthogonal organo- and metal catalysis strategy

Small-molecule modulators of biological targets play a crucial role in biology and medicine. In this context, diversity-oriented synthesis (DOS) provides strategies toward generating small molecules with a broad range of unique scaffolds, and hence three-dimensionality, to target a broad area of biological space. In this study, an organocatalysisderived DOS library of macrocycles was synthesized by exploiting the pluripotency of aldehydes. The orthogonal combination of multiple diversity-generating organocatalytic steps with alkene metathesis enabled the synthesis of 51 distinct macrocyclic structures bearing 48 unique scaffolds in only two to four steps without the need for protecting groups. Furthermore, merging organocatalysis and alkene metathesis in a onepot protocol facilitated the synthesis of drug-like macrocycles with natural-product-like levels of shape diversity in a single step.

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Reference£º
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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Medium-Ring Stereocontrol in the Temporary Silicon-Tethered Ring-Closing Metathesis Approach to the Synthesis of Polyketide Fragments

The temporary silicon-tethered ring-closing metathesis of chiral non-racemic allylic and homoallylic alcohols affords unsymmetrical Z-configured trisubstituted olefins that readily undergo stereoselective hydroboration and dihydroxylation to provide a novel approach to masked polypropionate and polyol fragments present in an array of biologically important natural products. For example, this strategy provides a convenient method for the construction of polyol fragments relevant to the secondary metabolites amphidinol 3 and lophodiol A, which have antifungal and cytotoxic activity, respectively.

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Reference£º
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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A unique ruthenium carbyne complex: A highly thermo-endurable catalyst for olefin metathesis

A cationic ruthenium carbyne complex was prepared and was found to initiate olefin metathesis reactions with good activities, which throws a new light on the design of a new type of ruthenium catalyst for RCM reactions. More importantly, no double bond isomerized by-product was observed even at elevated temperatures in reactions catalyzed by the new carbyne complex. A mechanism involving the in situ conversion of the ruthenium carbyne to a ruthenium carbene complex via addition of an iodide to the carbyne carbon was also proposed.

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Reference£º
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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Synthesis of 2,5-disubstituted dihydrofuran-3(2 H)-ones via [2,3]-sigmatropic rearrangement of oxonium ylides generated from alpha-oxo gold carbenes

Novel [2,3]-sigmatropic rearrangements of oxonium ylides generated from alpha-oxo gold carbenes were discovered. An efficient synthetic method of 2,5-disubstituted dihydrofuran-3(2H)-ones via gold-catalyzed intermolecular oxidation of the allyl homopropargyl ethers with N-oxide was developed. And the synthetic utility of the current method has been proved by concise formal synthesis of (¡À)-kumausallene. Georg Thieme Verlag Stuttgart, New York.

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Reference£º
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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New approaches to olefin cross-metathesis

New methodology for the selective cross-metathesis (CM) of terminal olefins employing ruthenium benzylidene 1 is described. CM with symmetric internal olefins was found to provide a useful means for homologating terminal olefins to protected allylic alcohols, amines, and esters. Due to the limited commercial availability of symmetric internal olefins, a two-step CM procedure was developed in which terminal olefins were first homodimerized prior to the CM reaction. Terminal olefins with allylic methyl substituents were observed to provide CM products in diminished yield albeit with markedly improved trans-selectivity. Reaction rates were measured for CM reactions utilizing butenediol and allyl alcohol derivatives, and the results demonstrated distinct advantages in reaction rate and stereoselectivity for reactions employing the disubstituted olefins. In the course of studies of substrates with allylic oxygen substituents, a new CM application was discovered involving the metathesis of acrolein acetal derivatives with terminal olefins. Acrolein acetals, including asymmetric variants derived from tartaric acid, proved to be exceptionally robust and trans-selective CM substrates. In related work, a pinacol-derived vinyl boronate was also found to be a reactive CM partner, providing a novel means for converting terminal olefins into precursors for the Suzuki coupling reaction.

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Reference£º
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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FUNCTIONALIZED LINEAR AND CYCLIC POLYOLEFINS

This invention relates to methods and compositions for preparing linear and cyclic polyolefins. More particularly, the invention relates to methods and compositions for preparing functionalized linear and cyclic polyolefins via olefin metathesis reactions. Polymer products produced via the olefin metathesis reactions of the invention may be utilized for a wide range of materials applications. The invention has utility in the fields of polymer and materials chemistry and manufacture.

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Reference£º
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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Synthesis of the first chiral PNA monomer labelled with a Fischer-type carbene complex

The synthesis, through a cross-metathesis reaction, of the first chiral peptide nucleic acid (PNA) monomer labelled with a Fischer-type carbene complex of chromium is reported. IR analysis of the new bioconjugate shows that the Cr(CO)4 moiety represents a suitable spectroscopic probe for diagnostic purposes.

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Reference£º
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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Stereoselective synthesis of the C1-C8 subunit of peloruside A

Two routes to the C1-C8 subunit of peloruside A are disclosed. The first route involving 14 steps exploits Krische’s allylation, substrate controlled 1,3-asymmetric induction during bromohydrin formation from an alkene utilizing an intramolecular sulfinyl group as a nucleophile and Pummerer reaction as key steps. The second, shorter, scalable route (seven steps) exploits catalytic asymmetric reactions including Jacobsen’s hydrolytic kinetic resolution of an epoxide and Sharpless’ asymmetric dihydroxylation reaction as the key steps.

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Reference£º
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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Enyne metathesis for the formation of macrocyclic 1,3-dienes

Macrocyclic 1,3-dienes of a variety of ring sizes are formed in good yield via enyne metathesis. Both endo- and exo-products are observed depending on the size of the macrocycle. In general, 10-membered rings and smaller give exo-products, while 12-membered rings and larger give endo-products. The endo/exo selectivity and the E/Z ratio of the diene products can be further controlled by the presence of ethylene in the reaction. Copyright

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Reference£º
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI

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A variable temperature NMR analysis and resonance assignment of the Grubbs second generation catalyst

The Grubbs second generation catalyst [RuCl2(PCy3)(H2IMes)CHPh] was analysed in solution in order to identify and assign all of the 1H and 13C NMR resonances. This was achieved through utilizing various 2D NMR techniques and by acquiring spectra at a range of different temperatures (?40 to 60 C). These assignments will aid researchers in future NMR studies of catalytic systems that employ the Grubbs catalyst by eliminating the resonances belonging to the catalyst and thus enabling the identification of any intermediates and/or new catalytic species. Restricted conformations and pi-stacking arrangement within the catalyst was also confirmed during this study.

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Reference£º
Highly efficient and robust molecular ruthenium catalysts for water oxidation,
Catalysts | Special Issue : Ruthenium Catalysts – MDPI