酚类糖苷缀合物的合成、表征及美白活性

根据拼合原理,以对苯二酚(p-HQ)、间苯二酚(m-HQ)及邻苯二酚(o-HQ)为先导化合物,通过一侧酚羟基的苄基保护、引入溴乙酸甲酯、还原、与3种糖元偶联、脱除保护基得到9种目标化合物。 同样以3-(4-羟基苯基)-1-丙醇为起始物质,通过苄基保护、与3种糖元偶联、脱除保护基得到3种目标化合物。 通过IR、¹H NMR、¹³C NMR、HRMS等波谱分析方法对所合成的12种目标化合物进行了结构表征。 对合成的酚类糖苷缀合物进行了美白活性研究。 结果表明,化合物p-HQ-6a、m-HQ-7a、p-HQ-6b、m-HQ-6b、o-HQ-6b、p-HQ-6c、m-HQ-7c、L-3a和L-4b对酪氨酸酶有抑制作用,其中o-HQ-6b和p-HQ-6c对酪氨酸酶的抑制作用优于阳性对照物α-熊果苷。     

Combined Claisen Rearrangement and Oxidative Cyclization as a Route to Hydroxymethyl Dihydrofuran‐Annulated Coumarins

A convenient and simple method for the synthesis of novel 3,4‐dihydrofuran‐annulated coumarins, 3‐(hydroxymethyl)‐2H‐furo[3,2‐c]chromen‐4(3H)‐ones 5a , 5b , 5c , 5d , 5e , 5f , 5g , by combined Claisen rearrangement and intramolecular regioselective oxidative cyclization of 4‐O‐allyl coumarin intermediates 3a , 3b , 3c , 3d , 3e , 3f , 3g using inexpensive oxidizing agent m‐CPBA is described. The reaction proceeds smoothly by tandem epoxidation/regioselective 5‐exo‐tet‐intramolecular ring opening. The structures of synthesized compounds are established on the basis of spectral data including IR, ¹H NMR, and mass and elemental analyses.     

Tandem RAFT Polymerization and Click Chemistry: An Efficient Approach to Surface Modification

PS grafted silica nanoparticles have been prepared by a tandem process that simultaneously employs RAFT polymerization and click chemistry. In a single pot procedure, azide‐modified silica, an alkyne functionalized RAFT agent and styrene are combined to produce the desired product. As deduced by thermal gravimetric and elemental analysis, the grafting density of PS on the silica in the tandem process is intermediate between analogous “grafting to” and “grafting from” techniques for preparing PS brushes on silica. Relative rates of RAFT polymerization and click reaction can be altered to control grafting density.

     

From QCA (Quantum Cellular Automata) to Organocatalytic Reactions with Stabilized Carbenium Ions

What do quantum cellular automata (QCA), “on water” reactions, and S_N1‐type organocatalytic transformations have in common? The link between these distant arguments is the practical access to useful intermediates and key products through the use of stabilized carbenium ions. Over 10 years, starting with a carbenium ion bearing a ferrocenyl group, to the 1,3‐benzodithiolylium carbenium ion, our group has exploited the use of these intermediates in useful and practical synthetic transformations. In particular, we have applied the use of carbenium ions to stereoselective organocatalytic alkylation reactions, showing a possible solution for the “holy grail of organocatalysis”. Examples of the use of these quite stabilized intermediates are now also considered in organometallic chemistry. On the other hand, the stable carbenium ions are also applied to tailored molecules adapted to quantum cellular automata, a new possible paradigm for computation. Carbenium ions are not a problem, they can be a/the solution!

     

Monoaurated vs. diaurated intermediates: causality or independence?

Diaurated intermediates of gold-catalysed reactions have been a long-standing subject of debate. Although diaurated complexes were regarded as a drain of active monoaurated intermediates in catalytic cycles, they were also identified as the products of gold–gold cooperation in dual–activation reactions. This study shows investigation of intermediates in water addition to alkynes catalysed by [(IPr)Au(CH₃CN)(BF₄)]. Electrospray ionisation mass spectrometry (ESI-MS) allowed us to detect both monoaurated and diaurated complexes in this reaction. Infrared photodissociation spectra of the trapped complexes show that the structure of the intermediates corresponds to α-gold ketone intermediates protonated or aurated at the oxygen atom. Delayed reactant labelling experiments provided the half life of the intermediates in reaction of 1-phenylpropyne (∼7 min) and the kinetic isotope effects for hydrogen introduction to the carbon atom (KIE ∼ 4–6) and for the protodeauration (KIE ∼ 2). The results suggest that the ESI-MS detected monoaurated and diaurated complexes report on species with a very similar or the same kinetics in solution. Kinetic analysis of the overall reaction showed that the reaction rate is first-order dependent on the concentration of the gold catalyst. Finally, all results are consistent with the reaction mechanism proceeding via monoaurated neutral α-gold ketone intermediates only.

Reaction kinetics and detected α-gold ketone intermediates reveal that gold-mediated hydration of alkynes does not rely on dual activation.     

Dynamic diastereoselectivity during iron carbonyl mediated spirocyclization reactions

Dynamic diastereoselectivity during Fe(CO)3 promoted [6+2] ene spirocyclization of 35a and 35b, having a chiral center on the pendent side chain, was investigated and gave rise to products 28a and 28b instead of four possible isomers. From this reaction, two chiral centers are generated, with absolute stereochemistry determined by the double bond geometry and the chiral center already present. 28a/b and the diene product from demetallation of 28a are proposed as potential intermediates for total synthesis of 18-deoxycytochalasin H. Furthermore, a stepwise second cyclization and a tandem double cyclization mediated by the Fe(CO)3 moiety was investigated.     

Acetogenic isoquinoline alkaloids: CXII. Separation and identification of dimeric naphthylisoquinoline alkaloids by liquid chromatography coupled to electrospray ionization mass spectrometry

The atropodiastereomeric dimeric naphthylisoquinoline alkaloids, michellamines A (1a), B (1b) and C (1c), together with their monomers, korupensamines A (2a) and B (2b), were investigated using electrospray ionization tandem mass spectrometry coupled to liquid chromatography (LC–ESI-MS–MS). From the spectra obtained, characteristic product ions were chosen to monitor the chromatographic separation achieved on an RP-18 column. Under acidic conditions required for chromatographic analysis, the monomeric alkaloids 2a and 2b yielded protonated molecules [M+H]⁺, while the dimers, the michellamines, exhibited doubly protonated [M+2H]²⁺ molecules. In addition, the coeluting alkaloids 1b and 2b were identified unambiguously by means of tandem mass spectrometry. Thus, together with the retention times of the alkaloids, the product ion spectra allowed us the identification of michellamines in the presence of their presumed biogenetic monomeric precursors. Application of the HPLC–MS–MS method successfully proved the enzymatic formation of michellamine C (1c) by in vitro dimerization of korupensamine B (2b).     

Amination of 4-nitropyridazine 1-oxides by liquid ammonia/potassium permanganate

Treatment of 4-nitropyridazine 1-oxide ( 1a ) 3-methoxy-6-chloro-4-nitropyridazine 1-oxide ( 1b ) or 3,6-dimethoxy-4-nitropyridazine 1-oxide ( 1c ) with a solution of potassium permanganate in liquid ammonia gives in reasonable-to-good yields the corresponding 5-amino-4-nitropyridazine 1-oxides (75%, 54% and 62%, respectively). 3,6-Dimethoxypyridazine ( 4a ) and 3-methoxypyridazine ( 4b ) are converted into the corresponding 4-aminopyridazines 6a,6b on treatment with potassium amide/liquid ammonia/potassium permanganate (yield 50 and 22% respectively). In the last-mentioned reaction besides 6b 3,3′-dimethoxy 4,4′-bipyridazine (7, 23%) was obtained. It is suggested that the neutral 1:1 σ-adducts formed between ( 1a–1c ) and liquid ammonia and the anionic σ-adducts, formed between ( 5a–5b ) and potassium amide are intermediates in this amino-oxidation reaction.     

Real-time, on-line monitoring of organic chemical reactions using extractive electrospray ionization tandem mass spectrometry

Extractive electrospray ionization mass spectrometry (EESI-MS) for real-time monitoring of organic chemical reactions was demonstrated for a well-established pharmaceutical process reaction and a widely used acetylation reaction in the presence of a nucleophilic catalyst, 4-dimethylaminopyridine (4-DMAP). EESI-MS provides real-time information that allows us to determine the optimum time for terminating the reaction based on the relative intensities of the precursors and products. In addition, tandem mass spectrometric (MS/MS) analysis via EESI-MS permits on-line validation of proposed reaction intermediates. The simplicity and rapid response of EESI-MS make it a valuable technique for on-line characterization and full control of chemical and pharmaceutical reactions, resulting in maximized product yield and minimized environmental costs. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Detection of intermediates in grignard reaction on the magnesium surface

Benzyl radicals and ion-radical pairs have been detected on a magnesium surface by electron spin resonance (ESR) spectroscopy during benzyl halide reactions with magnesium at low temperatures. The ratio of these intermediates depends on the carbon-halogen bond energy in the starting benzyl halide, the nature of the magnesium surface and the degree of magnesium aggregation. Polymagnesiumbenzyl chlorides were formed in small amounts and only monomagnesium organic compounds were formed from benzyl bromide and benzyl iodide.     

Intermediate detection in real time using reactive surface desorption dielectric‐barrier discharge ionization mass spectrometry

Reactive intermediates play key roles for reaction mechanism elucidation. A suitable tool for identifying the key intermediates is crucial and highly desirable. In this study, surface desorption dielectric‐barrier discharge ionization (reactive SDDBDI) was developed for characterization of the reactive intermediates. In reactive SDDBDI, the plasma is doped with a reagent before the plasma ions are directed at a cover slip surface bearing another analyte. Different from SDDBDI, reactive SDDBDI can be used both as an ambient ionization source and as a means to produce reagent ions for ambient ion/molecule reactions. The online derivation of 4‐aminophenol with trifluoroacetic anhydride demonstrated that reactive SDDBDI can be used for chemical analysis where improved specificity or sensitivity is required. The utility of this approach for real‐time detection of reactive intermediate was demonstrated by the Schiff‐base and Eberlin reactions. The formed intermediates and products could be readily detected and identified by tandem mass spectrometry. These results indicate that reactive SDDBDI can be used to generate reagent ions that undergo ion/molecule reactions in the open air with an analyte at condensed phase on a surface. Reactive SDDBDI has high‐efficiency ion transmission and high MS sensitivity. It is thus a potential tool to perform ambient ion/molecule reactions and detect reactive intermediates.     

Oxygen reduction reactions of monometallic rhodium hydride complexes

Selective reduction of oxygen is mediated by a series of monometallic rhodium(III) hydride complexes. Oxidative addition of HCl to trans-Rh(I)Cl(L)(PEt(3))(2) (1a, L = CO; 1b, L = 2,6-dimethylphenylisocyanide (CNXy); 1c, L = 1-adamantylisocyanide (CNAd)) produces the corresponding Rh(III) hydride complex cis-trans-Rh(III)Cl(2)H(L)(PEt(3))(2) (2a-c). The measured equilibrium constants for the HCl-addition reactions show a pronounced dependence on the identity of the "L" ligand. The hydride complexes effect the reduction of O(2) to water in the presence of HCl, generating trans-Rh(III)Cl(3)(L)(PEt(3))(2) (3a-c) as the metal-containing product. In the case of 2a, smooth conversion to 3a proceeds without spectroscopic evidence for an intermediate species. For 2b/c, an aqua intermediate, cis-trans-[Rh(III)(OH(2))Cl(2)(L)(PEt(3))(2)]Cl (5b/c), forms along the pathway to producing 3b/c as the final products. The aqua complexes were independently prepared by treating peroxo complexes trans-Rh(III)Cl(L)(η(2)-O(2))(PEt(3))(2) (4b/c) with HCl to rapidly produce a mixture of 5b/c and 3b/c. The reactivity of the peroxo species demonstrates that they are plausible intermediates in the O(2)-reduction chemistry of hydride complexes 2a-c. These results together show that monometallic rhodium hydride complexes are capable of promoting selective reduction of oxygen to water and that this reaction may be controlled with systematic alteration of the ancillary ligand set.     

微波促进Wittig-Michael串级反应立体专一性合成ω-氨基-β-D-呋喃核糖酸衍生物

以D-核糖为原料, 在微波促进下, 利用2,3-O-异丙叉基-D-核糖2与叶立德3(Ph₃PCHCOOEt) 的Wittig反应和Michael加成, 立体专一性地合成了β-D-呋喃核糖酸酯类化合物, 再经叠氮化及还原反应, 得到ω-氨基-β-D-呋喃核糖酸衍生物. 在微波辐射下, 该Wittig-Michael串级反应的效率得到显著提高, 反应时间由12 h缩短为10 min, 收率达到91%. 反应具有非常好的β-立体选择性, 在碱性条件下处理后, α-异构体可转变成热力学稳定的β-异构体, 从而得到单一的β-异构体. 计算结果表明, β-异构体4b比α-异构体4a具有更高的热力学稳定性.     

Prediction of NHC-catalyzed chemoselective functionalizations of carbonyl compounds: a general mechanistic map

Generally, N-heterocyclic carbene (NHC) complexed with carbonyl compounds would transform into several important active intermediates, i.e., enolates, Breslow intermediates, or acylazolium intermediates, which act as either a nucleophile (Nu) or an electrophile (E) to react with the other E/Nu partner. Hence, the key to predicting the origin of chemoselectivity is to compute the activity (i.e., electrophilic index ω for E and nucleophilic index N for Nu) and stability of the intermediates and products, which are suggested in a general mechanistic map of these reactions. To support this point, we selected and studied different cases of the NHC-catalyzed reactions of carbonyl compounds in the presence of a base and/or an oxidant, in which multiple possible pathways involving acylazolium, enolate, Breslow, and α,β-unsaturated acylazolium intermediates were proposed and a novel index ω + N of the E and Nu partners was employed to exactly predict the energy barrier of the chemoselective step in theory. This work provides a guide for determining the general principle behind organocatalytic reactions with various chemoselectivities, and suggests a general application of the reaction index in predicting the chemoselectivity of the nucleophilic and electrophilic reactions.

A novel index ω + N can be used to predict the chemoselectivity according to the general NHC-catalyzed reaction mechanism.     

Tropone Is a Mere Ketone for Cycloadditions to Ketenes

Tropone ( 1 ) reacts with ketenes 2 to yield [8+2] cycloadducts, the γ‐lactones 3 . The concerted [8+2] cycloaddition path is formally symmetry‐allowed, but we established that it is unfavorable. Careful low‐temperature NMR (¹H, ¹³C, and ¹⁹F) spectroscopies of the reaction of diphenyl ketene ( 2b ) or bis(trifluoromethyl) ketene ( 2c ) with tropone ( 1 ) allowed the direct detection of a β‐lactone intermediates 5b , c and novel norcaradiene species 6b , c in head‐to‐head configurations. The [2+2] cycloadducts 5b , c equilibrated with the norcaradienes 6b , c . The β‐lactones 5b and 5c were converted to the γ‐lactones 3b and 3c , respectively, in quantitative yields. The DFT calculations showed that the concerted [8+2] cycloaddition is unfavorable. The first step of the calculated reaction 1 + 2c is a cycloaddition which leads to a dioxetane intermediate. This initial [2+2] cycloadduct is isomerized to the β‐lactone 5c via the first zwitterionic intermediate. The β‐lactone 5c is further isomerized to the product γ‐lactone 3c via the second zwitterion intermediate. Thus, 3c is not formed via the well‐established two‐step mechanism including zwitterionic intermediates but via a five‐step mechanism composed of a [2+2] cycloaddition and subsequent isomerization (Scheme 12).     

Transformation of fused bicyclic and tricyclic beta-lactones to fused gamma-lactones and 3(2H)-furanones via ring expansions and O-H insertions

A two-step strategy for conversion of beta-lactones to gamma-lactones and 3(2H)-furanones was developed involving initial acyl C-O cleavage leading to delta-hydroxy-alpha-diazo-beta-ketoesters and beta-ketophosphonates. Subsequent tandem Wolff rearrangement/lactonization of these alpha-diazo intermediates provided cis-fused gamma-lactones efficiently under photolytic or thermolytic conditions. In addition, cis-fused 3(2H)-furanones were obtained by rhodium(II)-catalyzed O-H insertion reactions of the delta-hydroxy-alpha-diazo intermediates.     

Tandem cyclopropanation/ring-closing metathesis of dienynes

Certain dienynes give cyclorearrangement by tandem cyclopropanation/ring-closing alkene metathesis, triggered by either a ruthenium carbene or noncarbene ruthenium(II) precatalyst. The process represents a variation of enyne metathesis where presumed cyclopropyl carbene intermediates undergo a consecutive ring-closing metathesis. A mechanistic proposal is offered, and sequential use of catalysts provided a tandem ring-closing enyne/alkene metathesis product.     

Silver‐Catalyzed Allylation of Ketones and Intramolecular Cyclization through Carbene Intermediates from Cyclopropenes Under Ambient Conditions

Tandem C?C bond formation was achieved through silver‐catalyzed ring‐opening of cyclopropenes via carbene intermediates. The reaction of cyclopropenes in the presence of a silver catalyst gave indene derivatives under ambient conditions. In contrast, the insertion of organozinc reagents to silver carbene or allylic cation intermediates afforded allylmetal intermediates for the tandem allylation of carbonyl compounds.     

Carbene catalyzed umpolung of α,β-enals: a reactivity study of diamino dienols vs. azolium enolates,and the characterization of advanced reaction intermediates

Since their discovery by Bode and Glorius in 2004, N-heterocyclic carbene catalyzed conjugate umpolung reactions of α,β-enals have been postulated to involve the formation of diamino dienols (“homoenolates”) and/or azolium enolates (“enolates”), typically followed by addition to electrophiles, e.g. Michael-acceptors. In this article, we provide evidence, for the first time, for the postulated individual and specific reactivity patterns of diamino dienols (γ-C–C-bond formation) vs. azolium enolates (β-C–C-bond formation). Our study is based on the pre-formation of well defined diamino dienols and azolium enolates, and the in situ NMR monitoring of their reactivities towards enone electrophiles. Additionally, reaction intermediates were isolated and characterized, inter alia by X-ray crystallography.     

The ying and yang of asymmetric aminocatalysis

During the last six years the asymmetric catalysis of carbonyl transformations via iminium ion and enamine intermediates using chiral amines as organocatalysts has grown most remarkably. In this personal account an overview of this area is given. The field can be divided into two sub areas: (a) Iminium catalysis, which is typically used for cycloadditions and conjugate additions to enals and enones and (b) Enamine catalysis, which is commonly used in electrophilic alpha-substitution reactions of ketones and aldehydes. A common origin of the two catalysis principles is proposed and their recent merger in tandem sequences is discussed.