有机铋化学近十年的研究进展

铋及其化合物具有相对价廉、低毒性、低放射性等特点,已应用于医药、催化、化妆品和电子技术等领域。本文回顾了近10多年来有机铋化学的研究状况,主要从以下4个方面进行综述：（1）新型有机铋化合物的合成途径与结构特征;（2）有机铋化合物作为交联偶合、氧化、芳基化和其它反应的试剂;（3）作为催化剂;（4）作为生物医药用于溃疡、肿瘤和放射治疗等。文中着重于从分子水平关联新型有机铋化合物的结构与其化学和生物活性之间关系。此外,还介绍了有机铋化学研究领域的不足和今后的发展趋势。     

Efficient synthesis of fluorobenzyloxoimidazolidinone derivatives: precursors for the radiosynthesis of [F]fluorophenylamino acids

This paper describes an efficient synthesis of fluorobenzyloxoimidazolidinone derivatives. The title compounds 1a, 1b and 1c could be prepared with high diasteromeric purity (>99%) and overall yields of 19%, 48% and 41% in a ten or six-step synthetic procedure, respectively. These compounds are used as precursors for isotopic ¹⁸F-labelling.     

1,3-Dialkylimidazolium-2-carboxylates as versatile N-heterocyclic carbene-CO2 adducts employed in the synthesis of carboxylates and α-alkylidene cyclic carbonates

1,3-Dialkylimidazolium-2-carboxylate compounds of formulas 1a, 2, and 4 have been synthesized and fully characterized by X-ray spectroscopy quite recently. Up today, these compounds have found some interesting applications as precursors of N-heterocyclic carbenes (NHCs) used as ligands for metal-complexes or in the synthesis of organic compounds and ionic liquids. We have recently reported the use of 1-butyl, 3-methylimidazolium-2-carboxylate and 1,3-dimethylimidazolium-2-carboxylate in a CO₂-transfer reaction to CH₃OH and acetophenone for the synthesis of methylcarbonate and benzoylacetate. The scope of this CO₂-transfer reaction has been expanded to several organic compounds with active hydrogen (acetone, cyclohexanone, and benzylcyanide) for the synthesis of carboxylates of pharmaceutical interest, and to propargyl alcohols for the synthesis of α-alkylidene cyclic carbonates.     

Trifluoroacetaldehyde: A useful industrial bulk material for the synthesis of trifluoromethylated amino compounds

The synthesis of various trifluoromethylated amino compounds was studied using trifluoroacetaldehyde, an industrial bulk material, as a starting compound. One general application of trifluoroacetaldehyde is the preparation of trifluoroethylamino derivatives via reductive amination reaction. This synthesis includes the formation of the corresponding N,O-acetal intermediates followed by their reduction using NaBH₄ or 2-picoline borane complex, affording the target trifluoroethylamino compounds in moderate to good yields (47-87%).Another general application of trifluoroacetaldehyde is the synthesis of chiral α-substituted trifluoroethylamino compounds. In this synthesis, trifluoroacetaldehyde was first converted into the chiral trifluoromethyl tert-butyl sulfinimine, which was subjected to 1,2-nucleophilic addition reactions across its CN double bond. The addition of phenyllithium afforded α-(phenyl)trifluoroethylamino derivative in 83% yield and with 96% de. Allylation and Reformatsky reactions produced the corresponding α-substituted trifluoroethylamino derivatives in 82 and 58% yields and with 90 and 91% de, respectively.     

Nitro derivatives of 2,1,3-benzothiadiazole 1-oxides: synthesis,structural study,and NO release

A convenient one-pot synthesis of nitro derivatives of 2,1,3-benzothiadiazole 1-oxides by the reaction of o-nitroanilines with sulfur monochloride was developed. The structural features of 4-nitrobenzothiadiazole and its N-oxide were considered. High in vitro release of nitric oxide (69%) was found for a 6-nitro-2,1,3-benzothiadiazole sample by the Griess assay, which indicated good prospects for this class of compounds.     

Automated flow-through synthesis of heterocyclic thioethers

The fully automated, sequential flow-through synthesis of a 44-member array of thioethers 10[1-4,1-11] employing a resin "capture and release" reactor column is described. The array incorporates four different heterocyclic scaffolds, and the synthesis was performed using a custom-built robotic synthesizer that is able to (i) load and regenerate the reactor column and (ii) array each product into a single vial using UV threshold detection. All the compounds were obtained in high yield (>75%) and excellent purity (>95%) without the need for further purification.     

Electrochemical Synthesis of Organophosphorus Compounds on the Base of Elemental Phosphorus

Abstract

The straight synthesis of organophosphorus compounds on the base of white phosphorus may solve a lot of problems concerning with simplification technology proceeding as a whole. At present time we are investigating procedures for the electrochemical generation of organophosphorus compounds directly white phosphorus The ability to carry out this type of procedure in single step will have considerable environmental benefits. Thus procedure affording trialkylphosphates in a yield more than 90% and purity up to 98% for row material in undivided cell has been elaborated.     

Synthesis and biological evaluation of novel sulfonamide derivatives of tricyclic thieno[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones on melanin synthesis in murine B16 cells

Phototherapy with psoralens as photosensitizers is the commonly used method for the treatment of vitiligo. Considering the structure similarity between psoralens and thieno[2,3-d]pyrimidinones, a series of novel sulfonamide derivatives containing tricyclic thieno[2,3-d]pyrimidinone were synthesized and evaluated for melanin synthesis in murine B16 cells. All new compounds were characterized by ¹H NMR, ¹³C NMR, IR and HRMS (ESI). Among them, 6 compounds demonstrated excellent activity than positive control (8-methoxylpsoralen, 8-MOP) with more than 1.5-fold potency. Compound 11w with dichloro substitution at meta-positions in the benzenesulfonyl moiety was the most potent one (658.3 ± 8.7%), exhibiting 5.0-fold stronger activity than 8-MOP (130.9 ± 8.6%). The difluoro analog compound 11o increased melanin synthesis in murine B16 cells with a 4.35-fold potency as compared to 8-MOP. These compounds may serve as lead compounds for further drug discoveries for the treatment of vitiligo.     

Microbial deracemization of alpha-substituted carboxylic acids: substrate specificity and mechanistic investigation

A new enzymatic method for the preparation of optically active alpha-substituted carboxylic acids is reported. This technique is called deracemization reaction, which provides us with a route to obtain the enantiomerically pure compounds, theoretically in 100% yield starting from the racemic mixture. This means that the synthesis of a racemate is almost equal to the synthesis of the optically active compound, and this concept is entirely different from the commonly accepted one in the asymmetric synthesis. Using the growing cell system of Nocardia diaphanozonaria JCM3208, racemates of 2-aryl- and 2-aryloxypropanoic acid are deracemized smoothly and (R)-form-enriched products are recovered in high chemical yield (>50%). In addition, using optically active starting compounds and deuterated derivatives as well as inhibitors, we have disclosed the fact that a new type of enzyme takes part in this biotransformation, and that the reaction proceeds probably via the same mechanism as that in rat liver.     

α-thiocyanation of carbonyl compounds: A review

The α-thiocyanation of carbonyl compounds is one of the most important processes in synthetic organic chemistry. These compounds are important precursors for the production of various biologically important heterocyclic compounds and other industrially important products. Ammonium thiocyanate (NH₄SCN) is a key reagent for the production of such a class of thiocyanate intermediates. In addition to the inherent efficiency issues, there are also environmental concerns that need to be addressed. Therefore, in recent years considerable advances have been made for the synthesis of α-thiocyanation of carbonyl compounds with high selectivity and yield. In this review, we have summarized various methods for the synthesis of α-thiocyanation carbonyl compounds.     

Thiol-functionalized anthraquinones: mass spectrometry and electrochemical studies

Abstract  

In this work, the synthesis of various thiol-functionalized anthraquinone compounds is presented. The studied compounds were characterized by mass spectrometry and the main fragmentation pathways are discussed. The compounds studied formed stable self-assembled monolayers (SAMs) in the gold surface. The parameters for the reduction processes in the gold surface of the studied new anthraquinones were determined by cyclic voltamperometry tests.     

Real-time assessment of cigarette smoke particle deposition in vitro

Background

Recently, an increased interest in the identification of valuable possibilities for preserving the antioxidant properties of products obtained by thermal processing of fruits rich in bioactive compounds can be noticed. In this regard, an extensive analysis is necessary in terms of thermal processed products behavior in relation to various factors. The purpose of the present study was to assess the effect which processing and storage at 20°C has on the antioxidant properties and color quality of low-sugar bilberry jam with different low-methoxyl pectin (LMP) concentrations.

Results

For all measured parameters, it should be noted that thermal processing induced significant alterations reported to the values registered for fresh fruit. Most important losses due to thermal processing were recorded for total monomeric anthocyanins (TMA) (81-84%), followed by L-ascorbic acid (L-AsAc) content (53-58%), total phenolics (TP) content (42-51%) and FRAP (ferric reducing antioxidant power) values (36-47%). Moreover, depreciation of the investigated compounds occurred during storage at 20°C. Jam storage for 7 months resulted in severe losses in TMA content in the range 58-72% from the value recorded one day after processing. This coincided with marked increases in polymeric color percent of these products after 7 months of storage. Also, bilberry jam storage for 7 months resulted in a decrease in L-AsAc content of 40-53% from the value recorded one day after processing, 41-57% in TP content and 33-46% from the value recorded one day after processing for FRAP values. By decreasing of LMP concentration in the jam recipe from 1 to 0.3% there has been an increase in losses of investigated compounds.

Conclusion

Overall, the results indicated that bilberry jams can also represent a good source of antioxidant compounds, although compared to the fruit, important losses seem to occur. Practical application of this work is that this kind of information will be very useful in optimizing the jam processing technology and storage conditions, in order to improve the quality of these products.     

Development of a custom high-throughput preparative liquid chromatography/mass spectrometer platform for the preparative purification and analytical analysis of compound libraries

Solution-phase parallel synthesis has had a profound impact on the speed of compound synthesis delivering relatively pure compounds (>80%) in short order. However, to develop structure activity relationships (SAR) for a compound series, each library member should preferably be >95% pure. Historically, achieving and quantifying such high-purity criteria for each library member proved to be the slow step for most lead discovery groups. To address this issue, significant modifications have been made to a commercial Agilent preparative LC/MS system to allow for the general mass-guided purification of diverse compound libraries. The custom modifications include (1) the "DMSO slug" approach for the purification of samples with poor solubility; (2) an active splitter to reduce system back-pressure, reduce the delay volume, and allow for a variable split ratio; (3) a sample loading pump for the quick purification of large, dilute samples; (4) a preparative column-selection valve to quickly change column selectivity or sample loading; and (5) an analytical injector with a separate flow path for crude reaction or fraction analyses.     

Synthesis of symmetrical amino and aminomethyl derivatives of Tröger's base via Pd-catalyzed C-C and C-N bond formation

In this paper, we report the synthesis of amino and aminomethyl derivatives of Tröger's base (±)-1 and (±)-2. The key steps in the synthesis of (±)-1 and (±)-2 are Pd-catalyzed amination and cyanation, respectively, of the easily accessible dihalo derivatives (±)-3. These compounds are important intermediates in the synthesis of new ligands and building blocks for H-bonded supramolecular architectures.     

Integrating hydrogen production with anodic selective oxidation of sulfides over a CoFe layered double hydroxide electrode

Replacing the sluggish oxygen evolution reaction (OER) with oxidation reactions for the synthesis of complex pharmaceutical molecules coupled with enhanced hydrogen evolution reaction (HER) is highly attractive, but it is rarely explored. Here, we report an electrochemical protocol for selective oxidation of sulfides to sulfoxides over a CoFe layered double hydroxide (CoFe-LDH) anode in an aqueous-MeCN electrolyte, coupled with 2-fold promoted cathodic H₂ productivity. This protocol displays high activity (85–96% yields), catalyst stability (10 cycles), and generality (12 examples) in selective sulfide oxidation. We demonstrate its applicability in the synthesis of four important pharmaceutical related sulfoxide compounds with scalability (up to 1.79 g). X-ray spectroscopy investigations reveal that the CoFe-LDH material evolved into amorphous CoFe-oxyhydroxide under catalytic conditions. This work may pave the way towards sustainable organic synthesis of valuable pharmaceuticals coupled with H₂ production.

Replacing anodic OER with selective sulfide oxidation produces sulfoxide-related pharmaceutical compounds over a CoFe-LDH catalyst with enhanced HER, providing a sustainable protocol for valuable pharmaceuticals synthesis without external oxidants.     

High Throughput and High Speed Organic Synthesis in Drug Discovery: An Integration of Chemistry and Technology

Drug discovery is a complicated process that involves multiple synthetic chemistry tasks. Among them, lead generation and optimization is the core business in the discovery research. During the stage of lead generation, a large library of many thousands individual compounds will be screened against a biological target to identify a set of hits that showed desirable activity. Once a hit has been identified, analog synthesis and development of SAR around this hit and establishment of relationsh…     

Practical procedures for the preparation of N-tert-butyldimethylsilylhydrazones and their use in modified Wolff-Kishner reductions and in the synthesis of vinyl halides and gem-dihalides

In this work we develop practical chemistry for the preparation of N-tert-butyldimethylsilylhydrazone (TBSH) derivatives from carbonyl-containing compounds and show that these products serve as superior alternatives to simple hydrazones in Wolff-Kishner-type reduction reactions, in the Barton vinyl iodide preparation, in the synthesis of vinyl bromides, and in the synthesis of gem-diiodides, gem-dibromides, and gem-dichlorides. In our new procedure for silyl hydrazone synthesis, aliphatic and aromatic ketones and aldehydes are shown to undergo highly efficient coupling (typically >95% yield) to form the corresponding TBSH derivatives when combined with equimolar amounts of 1,2-bis(tert-butyldimethylsilyl)hydrazine (BTBSH) and a catalytic quantity of scandium trifluoromethanesulfonate (typically, 0.01 mol %), neat, or in solvent. Optimized procedures are provided for the use of TBSH derivatives in a Wolff-Kishner-type reduction protocol that proceeds at low temperature (23-100 degrees C) and in a single reaction flask. Similarly, protocols for the use of TBSH derivatives as precursors to vinyl halides and gem-dihalides are described in detail.     

Synthesis,properties, and application of 4-nitrosemicarbazones

The studies of the condensation of 4-nitrosemicarbazide (4-NSC) with various aldehydes and ketones resulted in the development of an approach to the synthesis of N-nitrosemicarbazones, promising high-energy and biologically active compounds. Subsequent treatment with amines and alkalis led to the synthesis of water-soluble salts of nitrosemicarbazones, as well as the corresponding semicarbazones. The reaction of N,N′-diisopropyl- or N,N′-di-tert-butyl-1,2-ethanediimine with 4-nitrosemicarbazide led to the synthesis of glyoxal bis(nitrosemicarbazone) derivatives. A computer-aided screening using the PASS software showed a probability of high biological activity for the compounds obtained, whereas antiarrhythmic properties of camphor nitrosemicarbazone potassium salt were confirmed in experiments in rats.     

CuSO4 · 5H2O: A Novel,Green, Reusable,and Environmentally Friendly Catalyst for the One-Pot,Four-Component Synthesis of β-Acetamido Carbonyl Compounds

Multicomponent reactions for the synthesis of β-acetamido carbonyl compounds have been gained considerable attention in organic synthesis. In this articles, aromatic aldehydes have been employed in a one-pot reaction with enolizable ketones, acetonitrile, benzonitrile, and acetyl chloride in the presence of copper(II) sulfate petahydrate at ambient temperature to afford the corresponding β-acetamido ketones in very good yields. New compounds are reported. The use of readily available copper(II) sulfate petahydrate as a reusable and recyclable catalyst makes this process quite simple, convenient, and environmentally friendly.     

Organocatalytic asymmetric vinylogous addition to quinones - formation of optically active alpha-aryl ketones

The first organocatalytic addition of dicyanoalkylidenes to quinones catalyzed by Cinchona alkaloids leading to formation of 1,4-diketone derivatives with high diastereomeric ratios (up to >98 : <2 dr) and enantioselectivities (up to 99% ee) has been developed; the optically active compounds obtained are useful for a number of transformations, e.g. the synthesis of optically active alpha-aryl ketones.