Comparison of facially amphiphilic biaryl dendrimers with classical amphiphilic ones using protein surface recognition as the tool

Facially amphiphilic biaryl dendrimers are compared with the more classical benzyl ether amphiphilic dendrimers for molecular recognition, using protein binding as the probe. The protein used for the proposed study is chymotrypsin (ChT). A generation-dependent binding affinity was observed with the benzyl ether dendrimers, while the affinities were independent of generation in the case of the biaryl dendrimers. Similarly, although the ligands incorporated in both dendrons are the same, the biaryl dendrimers are able to bind more proteins compared to the benzyl ether dendrimers. For example, G3-dendron of biaryl dendrimer can bind six molecules of chymotrypsin, whereas G3-analogue of benzyl ether dendrimers can bind only three molecules of chymotrypsin. This result is consistent with our hypothesis that the internal layers of the facially amphiphilic biaryl dendrons are solvent-exposed and accessible for recognition. In addition, the systematic size differences in dendrons were also used to gain insights into the substrate selectivity that the enzyme gains upon binding to a ligand scaffold.     

Synthesis of tetra-ortho-substituted, phosphorus-containing and carbonyl-containing biaryls utilizing a Diels-Alder approach

The application of the Diels-Alder approach to biaryls (DAB) is described for the synthesis of tetra-ortho-substituted biaryl compounds containing orthogonally functionalized substituents. The syntheses of phosphorus-containing, disubstituted alkynes and carbonyl-containing, disubstituted alkynes were accomplished in two to three steps from commercially available reagents. Subsequent Diels-Alder cycloadditions with a range of oxygenated dienes yielded the target biaryls. Further functionalization through palladium-couplings is demonstrated on the phosphorus-containing biaryls. In addition, selective manipulation of each of the remaining ortho substituents on the phosphorus-containing biaryls is demonstrated. One of these phosphorus-containing derivatives is utilized as a highly active catalyst for Suzuki coupling. For the carbonyl-containing series, a wide range of dienophile substituents were screened including esters, ketones, and amides. The key Diels-Alder cycloadditions proceeded smoothly with the commercially available 1-methoxy-1,3-cyclohexadiene to yield the resultant tetra-ortho-substituted biaryls with excellent regioselectivity. The scope of the cycloaddition process was also explored on the carbonyl-containing dienophiles with a series of cyclic dienes. Acyclic dienes were also screened; however, they did not prove effective in the Diels-Alder process with the carbonyl-containing acetylenes. The ability to isolate enantiomerically pure biaryl atropisomers using a benzyl oxazolidinone is disclosed. Finally, the subsequent conversion to an axially chiral anilino alcohol is also reported.     

A four step synthesis of violaceic acid

The total synthesis of the biaryl ether natural product violaceic acid (1) in four steps is described. The steps included a S_NAr reaction between phenol 7 and flouroarene 12 to afford the biaryl ether 13, selective reduction of a nitro group to an amine in the presence of an aldehyde, a Cu mediated Sandmeyer reaction and final hydrolysis to afford the target compound 1. The amine 14 was also converted into the known iodide 18 which gave impure 1 on Pd mediated hydroxide cross coupling.     

Exploration of synthetic strategies for the stereoselective preparation of novel tetrahydrofuran-containing biaryls: A high-pressure promoted Diels-Alder approach

Three stereoselective synthetic approaches to tetrahydrofuran-containing biaryl scaffolds are described. All approaches involve a high-pressure promoted Diels-Alder reaction of substituted diene with methyl propiolate to give, after aromatization, the corresponding biaryl. The tetrahydrofuran moiety can be created starting from aryl-Br or aryl-CO₂Me functional groups through a γ-phenylseleno ketone intermediate.     

Diels-Alder approach to tetra-ortho-substituted biaryls employing propargylic tertiary alcohols as dienophiles

The efficient synthesis of a series of tetra-ortho-substituted biaryls is described utilizing a Diels-Alder reaction between propargylic tertiary alcohols and cyclic oxygenated dienes. The successful resolution of one of the biaryls is achieved through derivatization with menthyl chloroformate followed by crystallization. The menthyl carbamate is cleaved under basic conditions to reveal enantiomerically pure biaryl compounds.     

不同代硝基芳基苄醚树枝配体轴向取代硅(Ⅳ)酞菁光物理性质的比较

在二氯硅酞菁轴向位置引入硝基芳基苄醚树枝配体是一种减少酞菁配合物聚集体形成,提高其光动力活性的有效方法。本文采用UV/Vis、稳态和瞬态荧光光谱法比较了1-3代硝基芳基苄醚树枝配体轴向取代硅(Ⅳ)酞菁的光物理性质。研究结果表明,随着轴向树枝配体代数的增加,Q带最大吸收峰强度增大,酞菁核荧光强度增强,荧光量子产率降低,荧光寿命增长。研究结果将为开发轴向取代硅(Ⅳ)酞菁配合物作为新型光敏剂提供重要的理论依据。     

Smaller building blocks form larger assemblies: aggregation behavior of biaryl-based dendritic facial amphiphiles

Synthesis and micellar behavior of biaryl-based benzyl ether dendritic molecules prepared from a new biaryl building block are described. The key objective of the study is to tune the size of individual dendritic molecules and investigate its effect on aggregation behavior of the resulting micelle-like assemblies. We show that the functional group placement in the building block influences flexibility of the dendritic backbone and interior volume available for packing the hydrophobic groups, which is reflected in different aggregation behavior and aggregate size of the two types of micellar assemblies.     

Synthesis of beta-hydroxy-beta-(fluoronitrophenyl)alanines: vital components in the assembly of biologically active cyclic peptides

[formula: see text] Numerous biologically active cyclic peptides, such as the antibiotic vancomycin, contain amino acid residues connected through side-chain biaryl or aryl-alkyl ether linkages. Nucleophilic aromatic substitution reactions have recently been shown to provide a general method for the formation of such ether linkages, and consequently the synthesis of functionalized fluoronitro-substituted aromatic amino acids is of great interest. Herein, a method for the stereospecific synthesis of 3-fluoro-4-nitro- and 4-fluoro-3-nitro-threo-beta-hydroxyphenylalanine is described.     

Complete pi-facial diastereoselectivity in Diels-Alder reactions of dissymmetric 2,4-cyclohexadienones

[reaction: see text] The studies in the Diels-Alder reactions of 5-methoxy-masked o-benzoquinone (1a, R = OMe) and simple dissymmetric 2,4-cyclohexadienones 1b-e with methyl vinyl ketone, styrene, and benzyl vinyl ether are described. The dienones 1b-e reacted with dienophiles to form syn adducts (dienophile approach is syn to allylic methoxy group) exclusively.     

A new, lipophilic p-alkoxybenzyl ether protecting group and its use in the synthesis of a disaccharide

[formula: see text] In contrast to major advances in the chemical synthesis of oligosaccharides, the methods of purification of the intermediates are essentially the same as they were decades ago. Here, the synthesis of p-(dodecyloxy)benzyl chloride is described and it is demonstrated that the new p-(dodecyloxy)benzyl ether protecting group can render a protected disaccharide sufficiently lipophilic for selective adsorption on C18 silica, thus sidestepping the expensive silica gel chromatography traditionally used for the isolation of protected oligosaccharides.     

An efficient one-pot asymmetric synthesis of biaryl compounds via Diels-Alder/retro-Diels-Alder cascade reactions

[reaction: see text] A single-step chirality transfer method for the synthesis of axially chiral biaryl compounds by construction of the second aromatic ring via a Diels-Alder/retro-Diels-Alder cascade reaction is reported. This methodology should find broad application in the synthesis of natural products and asymmetric catalysts.     

Regioselective synthesis of 2-amino-isophthalonitriles through a ring transformation strategy

An expeditious synthesis of several 2-amino-isophthalonitriles and their biaryl compounds is described and illustrated by carbanion-induced ring transformation of functionalized 2H-pyran-2-ones with malononitrile in excellent yields. The strength of the reaction lies in the creation of an aromatic ring at room temperature from six-membered lactones under mild reaction conditions. This approach is an alternative to Diels-Alder reactions of 2H-pyran-2-ones with dienophiles, which require forcing thermal conditions to obtain benzene derivatives.     

Intramolecular biaryl coupling reaction of benzyl benzoate and phenyl benzoate derivatives, and its application to the formal synthesis of (−)-steganone

Construction of the biaryl moiety of stegane and related compounds through an intramolecular biaryl coupling reaction is described. Undesired products were obtained by the intramolecular coupling reaction of benzyl benzoates (8, 13, and 14) because of their steric and electrostatic properties, and only that of phenyl benzoates (26b and 26c) afforded the desired biaryl lactones in good yields. An asymmetric formal synthesis of the title compound has been achieved using an enantioselective lactone-opening reaction followed by a four-step conversion to the known compound.     

Palladium‐Catalzyed Atroposelective 16‐Membered Macrocyclization: Total Synthesis of Isoplagiochin D†

Isoplagiochin D is a ring‐strained macrocyclic bisbibenzylis, which showed stable axial chirality in one biaryl structure, and semistable axial chirality in the other biaryl moiety. We reported here an unprecedented example for the catalytically asymmetric synthesis of ring‐strained atropisomers via Pd‐catalyzed macrocyclization between benzyl halides and carbenes. This newly developed Pd‐catalyzed asymmetric macrocyclization protocol enabled us a quick synthesis of isoplagiochin D in a highly enantioselective manner.     

Lewis Acid-Promoted, Stereocontrolled, Gram Scale, Diels-Alder Cycloadditions of Electronically Matched 2-Pyrones and Vinyl Ethers: The Critical Importance of Molecular Sieves and the Temperature of Titanium Coordination with the Pyrone

(R)-(+)-Binol-titanium coordinates with commercial methyl 2-pyrone-3-carboxylate and promotes mild, highly enantiocontrolled Diels-Alder cycloadditions with electron-rich vinyl ether CH(2)=CHOCH(2)-1-naphthyl and vinyl silyl ether CH(2)=CHOSiMe(2)Bu-t leading to valuable 1alpha,25-dihydroxyvitamin D(3) (calcitriol) intermediate (-)-2. Unexpectedly, two subtle variables were found to be critical for obtaining reproducibly over 90% enantioselectivities in gram scale cycloadditions: (1) the moisture content (15-17% is best) of the molecular sieves used to prepare the binol-titanium complex according to the Mikami protocol and (2) the temperature (50 degrees C is best) at which the pyrone ester is mixed with the binol-titanium complex. Unsubstituted 2-pyrone undergoes ytterbium-promoted, high-pressure, regioselective, and stereoselective Diels-Alder cycloaddition with benzyl vinyl ether to form versatile bicyclic lactone (+/-)-4 on gram scale.     

Aza Diels-Alder reactions utilizing 4-iodo-2-trimethylsilyloxy-butadiene

The aza Diels-Alder reaction is described for a novel diene. Imines bearing benzyl and aromatic protecting groups both work well. Moderate diastereoselectivities can be obtained using the simple α-methylbenzyl chiral auxiliary.     

Enantioselective total synthesis of (S)-bisoranjidiol, an axially chiral bisanthraquinone

The first enantioselective total synthesis of the bisanthraquinone (S)-bisoranjidiol and an unnatural regioisomer has been accomplished. Key features of the synthesis include the asymmetric oxidative biaryl coupling of a hindered 8-substituted 2-naphthol, selective para-quinone formation, and regioselective tandem Diels-Alder/aromatization reactions.     

Carbazole synthesis via an in situ trapping strategy with indolyl enol ethers

Indolyl enol ethers, generated from the alkoxy(indolyl)carbenium tetrafluoroborates 1 by treatment with sodium hydride, can be trapped with dimethyl acetylenedicarboxylate or N-phenylmaleimide to furnish the selectively functionalized carbazoles 3,4,5,9,10 , and 13. In addition, the biaryl derivatives 6 and 11 are produced by a ring-opening reaction of the primarily formed Diels-Alder adduct. In the case of the biaryl derivative 6 , an X-ray crystal structure analysis yields valuable information on constitutions and configurations in the biaryl series. The phenomenon of atropisomerism is discussed for this compound.     

New synthesis of arcyriaflavin-A via silyl enol ether-mediated and Fischer indolisations

A new synthesis of the natural product arcyriaflavin-A is described. It was brought about through Diels-Alder cycloaddition and two indolisations based on silyl enol ether nucleophilic attack and Fischer processes.     

Synthesis and Diels-Alder reactions of 9-(4-benzyloxazolin-2-yl) anthracene

The synthesis of 9-(4-benzyloxazolin-2-yl)anthracene is described employing a new approach for the cyclisation of β-hydroxy amides to oxazolines. Thermal Diels-Alder reactions with N-methyl maleimide were found to be considerably slower than those previously observed. Essentially no diastereoselectivity was observed in these reactions as the benzyl stereodirecting group is remote from the reactive site. Minor rate enhancements were noticeable in the presence of some added Lewis acids, but with no diastereoselection.