Nature-inspired catalytic asymmetric rearrangement of cyclopropylcarbinyl cation.

In nature, cyclopropylcarbinyl cation is often involved in cationic cascade reactions catalyzed by natural enzymes to produce a great number of structurally diverse natural substances. However, mimicking this natural process with artificial organic catalysts remains a daunting challenge in synthetic chemistry. We report a small molecule-catalyzed asymmetric rearrangement of cyclopropylcarbinyl cations, leading to a series of chiral homoallylic sulfide products with good to excellent yields and enantioselectivities (up to 99% enantiomeric excess). In the presence of a chiral SPINOL-derived N-triflyl phosphoramide catalyst, the dehydration of prochiral cyclopropylcarbinols occurs rapidly to generate symmetrical cyclopropylcarbinyl cations, which are subsequently trapped by thione-containing nucleophiles. A subgram-scale experiment and multiple downstream transformations of the sulfide products are further pursued to demonstrate the synthetic utility. Notably, a few heteroaromatic sulfone derivatives could serve as "covalent warhead" in the enzymatic inhibition of severe acute respiratory syndrome coronavirus 2 main protease.

Chiral sulfonimide as a Brønsted acid organocatalyst for asymmetric Friedel-Crafts alkylation of indoles with imines.

Binaphthyl-based chiral sulfonimide (CSI) is demonstrated for the first time to be an efficient, strong Brønsted acid in asymmetric organocatalysis. A series of CSIs were synthesized and screened in the asymmetric Friedel-Crafts alkylation of indoles with imines. Good to excellent yields and enantioselectivities have been achieved. It was proved that it was crucial to wash the CSI catalyst with HCl before use.

Anthracene capped isobenzofuran: a synthon for the preparations of iptycenes and iptycene quinones.

Anthracene capped isobenzofuran 5 (5,6-(9,10-dihydroanthracen-9,10-yl)isobenzofuran) was synthesized for the first time. It is a highly reactive and versatile synthon for the synthesis of iptycene derivatives via Diels-Alder reactions. Cycloadducts 10 could be readily deoxygenated to iptycenes 11. Two new reactions of PhI(OAc)(2)/TfOH have been explored. Endoxides 10 were directly oxidized to iptycene quinones 12, and isobenzofuran 5 was conveniently converted to triptycene dialdehyde 16. H-shaped centrally extended pentiptycene quinones 13 and 14 were also synthesized.

An easy assembled fluorescent sensor for dicarboxylates and acidic amino acids.

Two mesitylene based neutral receptors 1 and 2 bearing two thiourea binding sites were constructed as fluorescent probes for sensing dicarboxylates. Their binding affinities toward dicarboxylates, aspartate and glutamate have been investigated in acetonitrile solution by fluorescence titration experiments. Both fluorescent sensors exhibited some ability to discriminate the antipodal forms of aspartate and glutamate.

Ratiometric fluorescent probe for enantioselective detection of D-cysteine in aqueous solution.

A ratiometric fluorescent probe based on a Cd(2+)-ACAQ complex was designed and demonstrated for the chemo- and enantioselective detection of cysteine in 99:1 buffered HEPES:ACN solutions. Under the measuring conditions, the sensor demonstrates high selectivity toward Cys against Hcy and GSH, and an enantioselectivity of 3.35 can be achieved for antipodal forms of Cys.

Oxadisilole fused triptycene and extended triptycene: precursors of triptycyne and extended triptycyne.

With benzobisoxadisilole 1 as a 1,4-benzdiyne equivalent, oxadisilole fused triptycene 5 and extended triptycene 6 were synthesized. Triptycenes 5 and 6 are new precursors of triptycyne 7 and extended triptycyne 8 respectively via the phenyliodination/fluoride induced elimination protocol. Using these two arynes, a series of triptycene derivatives were synthesized.

A colorimetric and fluorescent turn-on chemosensor operative in aqueous media for Zn2+ based on a multifunctionalized spirobenzopyran derivative.

By conjugating spiropyran chloride 8 with 2-amino-N-(quinolin-8-yl)acetamide (5), multifunctionalized spirobenzopyran derivative SPQN was designed and synthesized as a water soluble colorimetric and fluorescent turn-on chemosensor for Zn(2+). In 50% aqueous ethanol buffer solution, SPQN displayed a selective chelation fluorescence enhancement (16-fold) at 650 nm and visible color change (from colorless to red) with Zn(2+) among the metal ions examined. In addition, as the third channel to display the metal binding characteristics of SPQN, operating on an efficient FRET process between the quinoline and the merocyanine moiety of the sensor, ratiometric determination of Zn(2+) can be realized.

Camphor sulfonyl hydrazines (CaSH) as organocatalysts in enantioselective Diels-Alder reactions.

Cyclic sulfonyl hydrazine was demonstrated for the first time as a new functionality for organocatalysis. A series of six-membered cyclic hydrazines derived from camphor sulfonic acid were synthesized. With trichloroacetic acid as cocatalyst, they are efficient organocatalysts for enantioselective Diels-Alder reactions with good chemical yields and up to 96% ee. The reactions took place in brine at 0 degrees C to room temperature.

Cholic acid-based fluorescent probes for enantioselective recognition of trifunctional amino acids.

The ditopic fluorescent photoinduced electron transfer (PET) amino acid sensory probes and were designed and synthesized from cholic acid. To confer the probes with specific binding ability, an amidothiourea moiety and a cyclic diamino-chiral receptive site were introduced on the C17 side chain and the C7 and C12 hydroxyl pendants, respectively. In acetonitrile, the probes demonstrated differential binding toward trifunctional amino acids like serine, lysine, threonine and tyrosine against other simple amino acids. Enantioselectivities (KD/KL) of up to 8.9 and sensitivities in the micromolar range with the probes were observed for trifunctional amino acids.

Oxadisilole-fused isobenzofurans. Synthesis and characterization of oxadisilole-substituted acenes.

Mono- and bis-oxadisilole-fused isobenzofurans were first synthesized and isolated. A series of mono-, bis-, and tris-oxadisilole-substituted acenes were then synthesized by benzyne Diels-Alder reactions with the isobenzofurans. The photophysical, redox, and thermal properties of these new acenes were characterized.

Enantiomeric separation and quantification of ephedrine-type alkaloids in herbal materials by comprehensive two-dimensional gas chromatography.

The separation of ephedrine-type alkaloids and their enantiomers in raw herbs and commercial herbal products was investigated by carrying out enantioselective separation in the first-dimension column (containing beta-cyclodextrin as the chiral selector) of a comprehensive two-dimensional gas chromatography (GC x GC) system, whereas a polar polyethylene glycol capillary column was used for separation in the second dimension. Naturally occurring ephedrine-type alkaloids and their synthetic analogues (enantiomeric counterparts) were adequately resolved from each other, as well as from potential interference species in the sample matrix using GC x GC, whereas single column GC analysis was unable to separate all the alkaloids of interest. Detection limits in the order of 0.1-1.3 microg/mL and linearity of calibration with R(2)>or=0.999 over approximately the range of 0.5-100 microg/mL for the quantitative determination of various ephedrine-type alkaloids were obtained. The commercial herbal products tested contained mostly (-)-ephedrine, (+)-pseudoephedrine, (-)-N-methylephedrine and (-)-norephedrine, with concentrations in the range of 40-2100, 0-1,300, 15-300 and 0-30 microg/g of the product, respectively, and repeatability of analysis was generally in the range of 1-5%. The present GCxGC method is effective and useful for the determination of the dosage levels of the principle ephedrine-type alkaloids in commercial health supplements and complex raw herb formulations, as well the differentiation of ephedrine-containing products that were derived from natural plant or synthetic sources, e.g., simply by visualizing the presence or absence of the enantiomeric pairs of (+/-) ephedrine and (+/-)-N-methylephedrine in the GC x GC chromatograms.

Fluorescent anion sensor derived from cholic acid: the use of flexible side chain.

[structure: see text] The fluorescent photoinduced electron transfer (PET) chemosensors 1-3 were synthesized from cholic acid. 1 and 2 containing amidothiourea groups as anion receptive sites demonstrated much higher affinity toward anions than 3 containing traditional thiourea H-bond donating group. Comparative studies on their binding affinity toward carboxylates, dihydrogen phosphate, and halides revealed that the amidothiourea moiety on the C17 side chain could work cooperatively with H-bond donating groups on C7 and C12 to bind spherical halogen anions. An unexpected specific fluorescence enhancement of 1 by coordinating bromide ion was observed.

Oligo(fluorenyleneethynylenegermylene)s and their metallopolymers.

Oligo(fluorenyleneethynylenegermylene)s and their polyplatinynes are synthesized and photophysically characterized; inclusion of heavy germylene bridges greatly boosts the phosphorescence decay rate in metallopolymers.

Generation of synthetic equivalents of benzdiynes from benzobisoxadisiloles.

Linear and angular benzobisoxadisiloles 14 and 16 can serve as the precursors for stepwise generations of the syntetic equivalents of 1,4- and 1,3-benzdiynes. Benzynes generated were trapped as [4+2] cycloaddition products. Two identical or different rings can be fused to the benzdiyne equivalents. Highly substituted arenes were obtained by removing the oxygen bridges from the furan adducts. The synthesis of naphthoxadisilole 28, which can serve as the precursor of 2,3-naphthyne, is also described.

Separation of enantiomers in microemulsion electrokinetic chromatography using chiral alcohols as cosurfactants.

A novel chiral microemulsion, which involved the use of chiral alcohols as cosurfactants, was demonstrated for the enantiomeric separation of a number of pharmaceutical drugs in microemulsion electrokinetic chromatography (MEEKC). The chiral alcohols investigated were optically active 2-alkanols, with the alkyl chain length having carbon number ranging from 4 to 7. The data indicated that, except for R-(-)-2-butanol, the use of R-(-)-2-pentanol, R-(-)-2-hexanol or R-(-)-2-heptanol as the chiral cosurfactant resulted in the baseline or partial resolution of most of the test solutes, i.e., (+/-)-norephedrine, (+/-)-ephedrine, DL-nadolol, and DL-propranolol. In addition to the chain length of the chiral 2-alkanols, the effects of other experimental conditions, such as the concentration and chirality of the 2-alkanols, as well as the pH of the run buffer and the oil phase of the microemulsion, on the enantiomeric separation of the test solutes were also investigated. An interesting finding was that the water-immiscible organic solvent (oil core) within the microemulsion droplets appeared to play an important role in the chiral separation mechanism. Also, the importance of hydrogen bonding between the test solutes ((+/-)-ephedrine and related compounds) and the chiral microemulsion was demonstrated, as it was not possible to resolve a pair of enantiomers which lacked a beta-amino proton (i.e., (+/-)-N-methyl ephedrine) under optimized run buffer conditions (e.g., 5.0% R-(-)-2-hexanol, 0.8% n-octane, and 3.5% SDS in 90.7% borate buffer at pH 9.2).

Stacking and separation of enantiomers by acetonitrile-salt mixtures in micellar electrokinetic chromatography.

The feasibility of employing the "acetonitrile stacking" method in micellar electrokinetic chromatography (MEKC) for the on-line preconcentration and separation of enantiomers is demonstrated for the first time. The effects of various experimental parameters on the stacking and separation of three different pairs of optical isomers, i.e., two substituted naphthyl enantiomers and one dansylated-DL-amino acid, were examined. In particular, the effectiveness of the addition of acetonitrile and salt in the sample matrix to induce narrowing of the analyte bands was investigated in the presence of sodium cholate as the chiral surfactant micelle in the separation buffer. For example, it was found that the presence of both acetonitrile and 1% NaCl in the sample matrix (volume ratio = 2:1) led to a significant improvement of the peak height and resolution for the MEKC separation of a pair of R(-)/S(+)-1,1'-binaphthyl diyl hydrogen phosphate enantiomers when the injection sample size was relatively large (e.g., 12% capillary volume). Furthermore, the feasibility of combining salting-out solvent extraction (off-line) and acetonitrile stacking (on-line) as a novel approach for sample preconcentration in capillary electrophoresis was also demonstrated.

A ratiometric fluorescent sensor for Ag(I) with high selectivity and sensitivity.

A bicyclic cycloadduct 1 bearing a pyrenyl moiety has been synthesized and investigated as a ratiometric fluorescent sensor for AgI. In an aqueous ethanol solution of 1, the presence of silver ion induces the formation of a 1:2 metal-ligand complex, which exhibits a strong intensity enhancement of the pyrene excimer emission at the expense of the emission of monomeric pyrene.

A new approach for asymmetric synthesis of (R)-3-methylpyrrolidine alkaloids from (S)-malic acid.

Diastereoselective methylation of dimethyl (S)-malate 7, followed by two, three-step reductive de-hydroxylation procedures afforded dimethyl (R)-2-methylsuccinate 11 in 80.2% e.e. and 84.7% e.e., respectively. The latter compound was further transformed into the natural enantiomers of the ant venom alkaloids (R)-leptothoracine 1 and (R)-3-methyl-N-(2-phenylethyl)-pyrrolidine 2.