Letters in Organic Chemistry - Volume 6, Issue 5, 2009

The preparation of a series of 1,5-disubstituted-4-methyl imidazoles is reported, based on an unprecedented reaction between an acetimine and TosMIC in the presence of tert-butylamine and catalytic amounts of bismuth(III) triflate. The mechanism is believed to involve formation of an imidazoline intermediate, followed by the methyl group migration, and subsequent aromatization to the imidazole ring.

Cross coupling metathesis reactions from two ethylenic compounds 4 and 5 easily led to Michael acceptors 6ab and 7a-b. Reaction of these compounds, or of enone 5', with p-toluenesulfonylmethyl isocyanide (TosMIC) provided the disubstituted pyrroles 9a-c and 10a-b. The analogous reaction of compounds 6a-b and 5', but in presence of Ph3SnCl, provided the trisubstituted pyrroles 11a-c. All of these compounds 9-11 were thus obtained in two steps only.

The Peterson reaction of (4R)-N-(trimethylsilyl)methyl-4-alkyloxazolidin-2-one gives (E/Z)-(4R)-N-(2',3'- diphenylbut-1'-enyl)-4-alkyloxazolidin-2-ones (enecarbamates) with increasing (Z)-selectivity and moderate-to-high diastereoselectivity in the individual E isomer as a function of increasing temperature. X-ray structure of the Peterson adduct, (4R,3'S)-N-(2',3'-diphenyl-2'-hydroxy-but-1'-enyl)-4-alkyloxazolidin-2-one (enecarbamates), reveals the rationale for the formation of a single isomer through syn elimination. The optically pure enecarbamates obtained with the Peterson adduct were further employed for photochemical and photophysical studies.

α-Bromoacetate esters of the azaphilone isochromene-6,8-dione core exhibit a pH-dependent orthogonal reactivity allowing for the one-pot cross-linkage of primary amines to thiols in an inter- or intramolecular fashion to afford fluorescent products. This represents a new potential strategy for bioconjugate chemistry.

One pot three component coupling of 3-alkynyl-4-isoquinoline carbonyl derivatives with Fischer carbene complexes and dienophiles leading to the synthesis of phenanthridine ring system has been investigated. This reaction involves the generation of furo[3,4-c]isoquinolines as transient intermediates, which undergo [4+2] cycloaddition with a dienophile in an inter/intramolecular fashion. In fact, this is the first report of the work on furo[3,4-c]isoquinoline intermediates.

Asymmetric electrophilic α-amination of aldehydes and ketones is described using trans-3-tert-butoxy-Lproline and trans-4-tert-butoxy-L-proline as efficient catalysts. Good yields and high enantioselectivities are obtained working at 0°C or at room temperature with a catalyst loading of only 5 mol%.

New 4-(1H-indol-3-yl)-6-arylpyrazolo[3,4-b]pyridines 7 have been prepared in a solvent-free three-component reaction induced by microwave from 5-aminopyrazole 1, benzaldehydes 2 and 3-indolyl-3-oxopropanenitrile 5. These compounds were also obtained by means of the reaction of aminopyrazole 1 with benzylidene-derivatives of 3-(1H-indol- 3-yl)-3-oxopropanenitrile 6, prepared in the reaction of 3-(1H-indol-3-yl)-3-oxopropanenitrile and aldehydes.

The synthesis of 1,3-diphenyl-5-arylpyrazoles via the reactions of 2,3-epoxy-1-phenyl-3-aryl-1-propanones with phenylhydrazine was carried out in 48-84% yields at 230 °C under solvent-free condition within 1.5 h. This method provides several advantages such as operational simplicity, higher yield and solvent-free.

The structure of penicillazine has been revised on the basis of hydrolysis reaction. Its absolute stereochemistry has been confirmed by X-ray diffraction using copper radiation. Eight new penicillazine derivatives (1-8) were prepared and some of them showed higher levels of activity than penicillazine against α-glucosidase and Human DNA topoisomerase I.

Asymmetric Diels-Alder reactions between aza-chalcone and cyclopentadiene (CP) catalyzed by the binaphthol-titanium (BINOL-Ti) in the presence of HMPA (80 mole %) were studied. The products were obtained with up to 87% ees.

Enantioselective conjugate addition of benzotriazole to α,β-enones catalyzed by prolinol derivatives with moderate yields and enantioselectivities was reported. Studies of stereoelectronic effects of the catalyst showed that the transition state could be of a hydrogen bonding activation mode, and fine tuning of the substituents on the aryl moiety of the catalyst is important for the reaction stereoselectivities.

Triselenium dicyanide (TSD) under microwave heating has been reported herein for the first time to be an efficient catalyst for the benzoin type condensation reaction and this has been applied for the synthesis of heteroins such as pteroin, quinoxaloin, quinoloin and pyridoin in moderate to good yields. Heteroin is produced by the dimerization of two molecules of N-heterocyclic aldehyde.

A novel simple version for highly regioselective or regiospecific substitution method of aromatic isoquinoline has been developed by utilizing the reaction condition of Bischler-Napieralski cyclization. The proposed reaction mechanism was successfully indirect confirmed. In this method, chloroiminium intermedium A was formed from the amide compound with phosphoryl chloride, and intramolecular cyclized was preceded. The final structure of aromatic isoquinoline was obtained through removing the acidic hydrogen atom by sodium borohydride served as a base rather than reductive agent as expected.

A novel fluorescent calix[4]arene derivative(1) with benzimidazole units as fluorophores and imino groups as ionophores at the upper rim has been synthesized in the cone conformation. Compound (1) was fully characterized by 1HNMR, 13C-NMR, IR and MS. The changes of UV-Vis spectra and fluorescent spectra upon metal ions complexation show compound (1) can selectively recognize Fe3+ and Cr3+ ions. The complexation ratio of compound (1) and Fe3+ or Cr3+ is 1:1. The association constant of compound (1) for Fe3+ was 3.4x104 and for Cr3+ was 2.8x105.

A new series of α,α-disubstituted aziridinemethanols have been synthesized and their aza-Payne rearrangement reactions were studied. The results show that α,α-disubstituted aziridinemethanols with electron-withdrawing groups accelerate the aza-Payne rearrangement than those with electron-donating groups. All of the rearrangements proceeded through an inversion of configuration at the C-2 carbon.

Isoflavonoids containing a perfluoroalkylsulfonyloxy group were synthesized by perfluoroalkylsulfonylation of hydroxyisoflavones. The reaction showed high regioselectivity. Inhibitory effects of the synthesized isoflavones against proliferation of HL-60 and BEL-7402 cells were tested in vitro. Two isoflavones displayed strong inhibitory effect on HL- 60 cells.

To develop a methodology for delivering anabolic agents statins to bone, a bone targeting bisphosphonate was used as a carrier of drugs. Four statin-bisphosphonate conjugates were synthesized and examined for their bone mineral affinity in vitro by hydroxyapatite absorption method. The conjugates showed high binding activity with HAP, implying the modified statins possess the potential of bone targeting property.

A simple, mild and efficient method has been developed for the oxidation of alcohols to aldehydes and ketones using Oxone® as oxidant catalyzed by n-Bu4NBr at room temperature in water under UV lamp for 1 h. Oxone® smoothly oxidizes benzyl alcohol and its derivatives, benzhydrol and its derivatives.

The crude polysaccharide (SCP) extracted from Schisandra chinensis by hot water extraction and ethanol precipitation, was further fractionated by DEAE-cellulose and Sephacryl S-300 chromatography, giving a polysaccharide fraction named as SCP-BII. The molecular weight of SCP-BII was 23 kDa using HPGPC. Gas chromatography analysis suggested that SCP-BII was composed of rhamnose, arabinose, mannose, galactose, glucose and galacturonic acid with a ratio of 4.7:2.6:0.8:5.6:1:5.6. Pharmaceutical experiments showed SCP-BII administered in alloxan-induced diabetic mice can significantly reduce blood glucose levels and water intake, and increase the body weight of diabetic mice. The results suggest SCP-BII attenuated the diabetes-induced weight loss, polydipsia and hyperglycemia, and these improvements suggest that Schisandra chinensis could be considered as a potential anti-diabetic agent.