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MandelalideA and three congeners had recently been isolated as the supposedly highly cytotoxic principles of an ascidian collected off the South African coastline. Since these compounds are hardly available from the natural source, a concise synthesis route was developed, targeting structure 1 as the purported representation of mandelalideA. The sequence involves an iridium-catalyzed two-directional Krische allylation and a cobalt-catalyzed carbonylative epoxide opening as entry points for the preparation of the major building blocks. The final stages feature the first implementation of terminal acetylene metathesis into natural product total synthesis, which is remarkable in that this class of substrates had been beyond the reach of alkyne metathesis for decades. Synthetic 1, however, proved not to be identical with the natural product. In an attempt to clarify this issue, NMR spectra were simulated for 20 conceivable diastereomers by using DFT followed by DP4 analysis; however, this did not provide a reliable assignment either. The puzzle was ultimately solved by the preparation of three diastereomers, of which compound 6 proved identical with mandelalideA in all analytical and spectroscopic regards. As the entire “northern sector” about the tetrahydrofuran ring in 6 shows the opposite configuration of what had originally been assigned, it is highly likely that the stereostructures of the sister compounds mandelalidesB-D must be corrected analogously; we propose that these natural products are accurately represented by structures 68-70. In an attempt to prove this reassignment, an entry into mandelalidesC and D was sought by subjecting an advanced intermediate of the synthesis of 6 to a largely unprecedented intramolecular Morita-Baylis-Hillman reaction, which furnished the gamma-lactone derivative 74 as a mixture of diastereomers. Whereas (24R)-74 was amenable to a hydroxyl-directed dihydroxylation by using OsO4/TMEDA as the reagent, the sister compound (24S)-74 did not follow a directed path but simply obeyed Kishi’s rule; only this unexpected escape precluded the preparation of mandelalidesC and D by this route. A combined spectroscopic and computational (DFT) study showed that the reasons for this strikingly different behavior of the two diastereomers of 74 are rooted in their conformational peculiarities. This aspect apart, our results show that the OsO4/TMEDA complex reacts preferentially with electron deficient double bonds even if other alkenes are present that are more electron rich and less encumbered. Finally, in a brief biological survey authentic mandelalideA (6) was found to exhibit appreciable cytotoxicity only against one out of three tested human cancer cell lines and all synthetic congeners were hardly active. No significant fungicidal properties were observed.

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

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A de novo synthetic method towards apiose, a structurally unusual furanose, is reported. The key feature is sequential metal catalysis consisting of the palladium-catalyzed asymmetric intermolecular hydroalkoxylation of an alkoxyallene and subsequent ring-closing metathesis (RCM). This strategy enabled the efficient synthesis of various apiose-containing disaccharides and a unique convergent synthesis of trisaccharides.

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

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The scope of the catalyst-free water-based Mukaiyama aldol reaction was explored through its application to the site-selective functionalization of N-terminal aldehydes of peptides and proteins. Various functional groups were introduced under mild and environmentally friendly conditions, with the first demonstration of aldol C-C bond formation in protein labeling studies. The efficiency and speed achieved in protein labeling can be of special interest in chemical biology studies.

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

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Ryanodol (1) exists in nature in the form of the 1H-pyrrole-2-carboxylate ester derivative known as ryanodine, which is a potent modulator of the calcium release channel. The pentacyclic ABCDE-ring system of 1 is fabricated with eight oxy groups, three methyl groups, and one isopropyl group. All the eight tetrasubstituted stereocenters are concentrated within the 10-carbon ABDE framework. The total synthesis of this exceptionally complex molecule was achieved in 22 steps from the simple C2-symmetric tricycle 8. The synthetic route is based on installation of the seven stereogenic centers and formation of the four C-C bonds within the highly congested multicyclic format. The novel and flexible strategy developed here will enable the generation of chemical derivatives with different functional properties toward calcium release channels.

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

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The first catalytic, broadly applicable, efficient, gamma-, diastereo-, and enantioselective method for addition of O-substituted allyl-B(pin) compounds to phosphinoylimines (MEM=methoxyethoxymethyl, pin=pinacolato) is presented. The identity of the most effective catalyst and the optimal protecting group for the organoboron reagent were determined by consideration of the steric and electronic requirements at different stages of the catalytic cycle, namely, the generation of the chiral allylboronate, the subsequent 1,3-borotropic shift, and the addition step. Aryl-, heteroaryl-, alkenyl- and alkyl-substituted vicinal phosphinoylamido MEM-ethers were thus accessed in 57?92 % yield, 89:11 to >98:2 gamma:alpha selectivity, 76:24?97:3 diastereomeric ratio, and 90:10?99:1 enantiomeric ratio. The method is scalable, and the phosphinoyl and MEM groups may be removed selectively or simultaneously. Utility is highlighted by enantioselective synthesis of an NK-1 receptor antagonist.

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

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The first catalytic, broadly applicable, efficient, gamma-, diastereo-, and enantioselective method for addition of O-substituted allyl-B(pin) compounds to phosphinoylimines (MEM=methoxyethoxymethyl, pin=pinacolato) is presented. The identity of the most effective catalyst and the optimal protecting group for the organoboron reagent were determined by consideration of the steric and electronic requirements at different stages of the catalytic cycle, namely, the generation of the chiral allylboronate, the subsequent 1,3-borotropic shift, and the addition step. Aryl-, heteroaryl-, alkenyl- and alkyl-substituted vicinal phosphinoylamido MEM-ethers were thus accessed in 57?92 % yield, 89:11 to >98:2 gamma:alpha selectivity, 76:24?97:3 diastereomeric ratio, and 90:10?99:1 enantiomeric ratio. The method is scalable, and the phosphinoyl and MEM groups may be removed selectively or simultaneously. Utility is highlighted by enantioselective synthesis of an NK-1 receptor antagonist.

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

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New generations of Hoveyda and bis-carbene type of ruthenium-based olefin metathesis catalysts (10 and 12), containing cationic cyclic alkyl amino carbene (CAAC) ligands, have been synthetized. The catalysts show exceptional stability and activity in environmentally benign, protic media. Various olefin metatheses reactions of OH functionalized feedstock (e. g. RCM, ROMP CM) can be carried out at as low as 0.05 mol % catalyst loading in methanol, isopropanol, water or methanol/water solvent mixture, accomplishing the lowest applied catalyst loading reported so far in these media. The facile olefin metathesis of renewable feedstocks including phospholipids (23) and vegetable oils (20) in protic media has also been demonstrated.

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

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Infections caused by Mycobacterium tuberculosis kill more than 1.8 million people each year. While the persistence of this pathogenic bacterial species and the emergence of multidrug resistant strains have created an urgent need for new TB therapies, a new TB-specific drug has not been developed in over 40 years. The disclosure herein provides short and scalable syntheses of small molecules, and small molecules as new therapeutics for eradicating this life threatening pathogen.

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

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Diketo-1,3-dioxin-2-ones underwent retro-Diels-Alder reaction on heating in toluene at 110C to generate alpha,gamma,epsilon-triketo-ketenes. These were trapped with alcohols to provide 2,4,6-triketocarboxylates, which were smoothly aromatized by sequential reaction with potassium carbonate and methanolic hydrogen chloride to give resorcylate esters. The reaction was applied in the total synthesis of the marine antifungal agents 15G256beta (1), 15G256iota (2), and 15G256pi (3) and the mycotoxin S-(-)-zearalenone (4).

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

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A norbornene-functionalized derivative of acetylacetone has been used to synthesize a series of new polymerizable norbornene-derivatized phosphorescent platinum complexes of the form Pt(C?N)(O?O*) where C?N represents a cyclometalated ligand and O?O* represents the functionalized acetylacetonate ligand. The complexes have been fully characterized, and the structures of three examples have been determined by X-ray diffraction. Solution absorption and luminescence spectra and electrochemical data are very similar to those for analogues without these polymerizable groups. A 9,9-dialkyl-2,7-di(carbazol-9-yl)fluorene material, in which one of the alkyl groups bears a norbornene group, has been synthesized and copolymerized with the Pt(C?N)(O?O*) complexes using Grubbs ruthenium catalysts, resulting in copolymers with broad molecular weight distributions. The copolymers have been used as lumophores in organic light-emitting diodes, thus demonstrating that platinum phosphors can be successfully integrated into the “hybrid” approach to organic light-emitting diodes, in which molecules with transport or luminescent properties are covalently attached to electronically inert polymer backbones to give solution-processible materials. Emission from aggregate states appears to play a similar role in these copolymers to that seen in vapor-deposited devices based on small phosphor and host molecules; in particular, considerable aggregate emission is observed when a phosphor with blue solution emission is used in the devices.

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