Asymmetric Synthesis of (R)-Fluoxetine: A Practical Approach Using Recyclable and in-situ Generated Oxazaborolidine Catalyst

A practical route for the synthesis of (R)-fluoxetine•HCl (ee＝96%) in 56% overall yield was described. The key intermediate (R)-3-chloro-1-phenyl-1-propanol was obtained by the asymmetric reduction of prochiral 3-chloropropiophenone using in-situ generated oxazaborolidine catalyst derived from (S)-α,α-diphenylprolinol. The chiral procatalyst (S)-α,α-diphenylprolinol was recovered quantitatively and recycled. An improved practical synthesis of (S)-α,α-diphenylprolinol was also discussed.     

5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇的合成

以5-雄烯二醇为原料,用微生物转化的方法合成了两个重要的神经甾体5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇。所用菌种总枝毛霉为我们自己筛选,并首次应用于5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇的合成中。     

Synthesis and Characterization of α-Bromo Chalcone Derivatives

α-Bromo chalcones containing 2-thiene ring were prepared in good yields by the condensation of 1-(thien-3-yl)ethanone with aromatic aldehydes, followed by bromination with bromine and selective dehydrobromination with triethyl amine at room temperature.     

Stereoselective Cycloaddition of N-Acyliminium Ions with α,β-Unsaturated Ketones and Esters

The [4+2] reactions of N‐acyliminium ions, produced from 2‐aryl‐3‐hydroxy‐2,3‐dihydroisoindol‐1‐ones or 5‐hydroxy‐1‐phenyl‐2,5‐dihydro/2,3,4,5‐tetrahydropyrrol‐2‐ones in the presence of BF₃OEt₂, with α,β‐unsaturated ketones or esters were examined, and the dependence of these reactions on the substituents at double bonds was clarified. For β‐aryl substituted α,β‐unsaturated ketones and esters such as 4‐aryl‐3‐buten‐2‐ones, chalcones and methyl cinnamate, the [4+2] reactions could proceed smoothly at room temperature to afford 6‐acyl‐5,6,6a,11‐tetrahydroisoindolo[2,1‐a]quinolin‐11‐ones and 4‐acyl‐1,3a,4,5‐tetrahydropyrrolo[1,2‐a]quinolin‐ 1‐ones or 4‐acyl‐1,2,3,3a,4,5‐hexahydropyrrolo[1,2‐a]quinolin‐1‐ones in moderate to high yields; while for simple α,β‐unsaturated ketones and esters such as methyl crotonate and ethyl 3‐methylbut‐2‐enoate, except mesityloxide, the [4+2] reactions were difficult to proceed. The cycloaddition reactions were highly stereoselective, and only one stereoisomer was produced in each reaction.     

Ceramic Filter Balls Loaded with α-Fe2O3 and Their Application to NH3-N Wastewater Treatment

Hydrolysis reaction of Fe(NO₃)₃ at a high temperature in the presence of urea as the homogeneous precipitant was studied. With the prepared ceramic filter balls loaded with α-Fe₂O₃ after high temperature calcination, the loading of α-Fe₂O₃ on the porous ceramic filter balls from Fe(NO₃)₃ solutions of different concentrations and mechanical stability of the loaded α-Fe₂O₃ were studied. The product was characterized using XRD and SEM. Adsorption experiments were conducted to evaluate the performance of the product in adsorbing NH₃-N. It turned out that the specific surface area of the ceramic filter balls loaded with α-Fe₂O₃ had increased to 36.5387 m²/g from original 4.6127 m²/g. When the concentration of Fe(NO₃)₃ was 0.40 mol/L, the loading of α-Fe₂O₃ on the ceramic filter balls accounted for 8.4% of the total mass of the adsorbent and α-Fe₂O₃ was adsorbed on the filter balls very well. The adsorption isotherm of NH₃-N on the ceramic filter ball adsorbent loaded with α-Fe₂O₃ was of Langmuir type. The saturated adsorption capacity was 3.33 mg/L, and the adsorption constant K was 0.1873. NH₃-N was adsorbed by α-Fe₂O₃ more easily, which was a kind of specific adsorption.     

Studies on Hydroiodination and Deconjugation of 5—Aryloxy—（thiophenyl）—3—pentyn—2—one

One-pot hydroiodination and deconjugation of 5-aryloxy(or thiophenyl)-3-pentyn-2-one with a reagent system of sodium iodide/trimethylsilyl chloride/water in acetonitrile at 25℃ have been described.The plasuible mechanism was discussed.The reaction provided a simple and useful method for the preparation of (Z)-β-substituted β，γ-enones and (Z)-β-substituted α，β-unsaturated ketones.     

Selective α-Bromination of β-Keto Esters in Reusable PEG-400 under Mild and Catalyst-free Conditions

An efficient bromination protocol for the synthesis of α-bromo-β-keto esters has been developed. In PEG-400 （poly（ethylene glycol-400））, a variety of β-keto esters were treated with NBS （N-bromosuccinimide） at room temperature to selectively afford the corresponding α-monobromination products in excellent yields. It is noteworthy that the reaction was conducted under mild, environmentally benign and catalyst-free conditions.     

Cross-aldol Condensation of Cycloalkanones and Aromatic Aldehydes in the Presence of Nanoporous Silica-based Sulfonic Acid (SiO2-Pr-SO3H) under Solvent Free Conditions

The aromatic aldehydes underwent cross aldol condensation with cycloalkanones in the presence of a catalytic amount of nanoporous silica-based sulfonic acid (SiO2-Pr-SO3H) under solvent-free conditions to afford the corresponding α,α’-bis(substituted benzylidene)cycloalkanones in excellent yields with short reaction time without any side reactions. This method is very general, simple and environmentally friendly in contrast with other existing methods. SiO2-Pr-SO3H was proved to be an efficient heterogeneous solid acid catalyst, which could be easily handled and removed from the reaction mixture by simple filtration, and also recovered and reused without loss of reactivity.     

过无溶剂、无催化的aza-Michael加成反应合成b氨基酸衍生物

本文报道一种安全,环境有好,经济实用的合成b氨基酸衍生物的新方法。利用α,β不饱和化合物和脂肪族胺,通过无溶剂、无催化的aza-Michael加成反应,高产率的合成b氨基酸衍生物。     

Addition of Acetone towards β-Cyano-α-oxoesters Catalyzed by L-Proline: Dynamic Kinetic Resolution

β‐Cyano‐α‐oxoesters were found to undergo asymmetric aldol addition reaction with acetone in the presence of 10 mol% of L‐proline. With the racemic starting material, dynamic kinetic resolution (DKR) was achieved in quantitative yields with good diastreroselectivity of up to 85:15 dr and excellent ee up to 99% for the major diastereomer.     

A Facile Method for the Epoxidation of Cyclic Enone Catalyzed by tert-BuNH2 with 30% Hydrogen Peroxide as Oxidant

It was found that tert-BuNH_2 is an efficient catalyst for epoxidation of α,β-unsaturated ketones with 30% H_2O_2under mild conditions.For most of the cyclic unsaturated ketones used,moderate to excellent yields (45%—93%)were obtained within 24 h period.     

PPA-SiO2 Catalyzed Multi-component Synthesis of N-[α-(β-Hydroxy-α-naphthyl)(benzyl)] O-Alkyl Carbamate Derivatives

Silica-supported polyphosphoric acid (PPA-SiO2) was found to be an efficient catalyst for the multi-component condensation reaction of benzaldehydes, 2-naphthol, and methyl/benzyl carbamate to afford the corresponding N-[α-(β-hydroxy-α-naphthyl)(benzyl)] O-alkyl carbamate derivatives in good to excellent yields. This new approach consistently has the advantage of short reaction time, high conversions, clean reaction profiles, and simple experimental and work-up procedures.     

Highly Efficient InBr3 Catalyzed Michael Addition of Indoles to α, β-Unsaturated Esters

A highly efficient synthetic strategy toward Michael addition of indoles to α,β‐unsaturated esters has been developed using Lewis acid InBr₃ as catalyst. The reactions generated 3‐substituted indoles in high yields with excellent regio‐selectivity in the presence of catalytic amount of InBr₃ under mild reaction conditions. The method is simple, efficient and practical.     

胸腺素α1类似物的定点PEG修饰及其免疫活性评价

PEG修饰是改善蛋白质及肽类药物药代动力学特性的有效途径。然而与蛋白质相比，肽类化合物的分子较小，PEG的分子体积较大，其长链很可能会遮蔽肽的活性位点。因此，肽类化合物PEG修饰的位置和数量对于保持肽的生物活性至关重要。为阐明PEG修饰的位置与肽生物活性之间的关系，对肽类药物日达仙（胸腺素α1，Tα1）进行了定点修饰。Tα1具有α-螺旋、β-转角和无规卷曲的结构区域。分别在这些区域选择不同的位点进行PEG修饰。PEG的定点修饰是通过引入Cys，利用其-SH与mPEG-MAL的特异性反应而实现的。Con A刺激下的脾细胞产生IFN-γ试验的初步结果表明，PEG修饰对活性的影响与修饰的位置有一定的关系，大多数情况下，PEG修饰能保持Tα1的免疫活性。PEG修饰的位点对于保持肽的生物活性是很重要的。     

新型含苯并噻唑α-氨基膦酸酯类化合物在淀粉类手性固定相上的液相色谱分离

本文运用涂敷型(Chiralpak AD-H)和键合型(Chiralpak IA)两种淀粉类手性固定相高效液相色谱法,进行了新型含苯并噻唑α-氨基膦酸酯类化合物的手性分离。从色谱分离的保留因子(k)、分离系数(α)和分离度(Rs)三个方面考察了两种类型色谱柱的分离性能,上述化合物在Chiralpak IA柱上能够得到较好的基线分离。同时,讨论了温度、流动相极性和目标分析物的结构等因素对Chiralpak IA柱分离性能的影响。由于键合型固定相较稳定的性能,使某些非常规的溶剂(如THF)成功地应用于手性α-氨基膦酸酯类化合物的分离。     

Equilibrium Studies on Reactive Extraction of α-Cyclohexylmandelic Enantiomers Using Hydrophilic β-Cyclodextrin Derivatives Extractants

β‐Cyclodextrin (β‐CD) is negligibly soluble in organic liquids and can be modified to achieve a higher solubility in water. In this paper, racemic α‐cyclohexyl‐mandelic acid (α‐CHMA) was separated by chiral reactive extraction with aqueous β‐cyclodextrin derivatives. Hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD), hydroxyethyl‐β‐cyclodextrin (HE‐β‐CD), and methyl‐β‐cyclodextrin (Me‐β‐CD) were selected as chiral selectors for reactive extraction of α‐CHMA enantiomers from organic phase to aqueous phase. Factors affecting the extraction efficiency were investigated, including the types of organic solvents and β‐CD derivatives, the concentrations of the chiral selector and α‐CHMA enantiomers, pH and temperature. The experimental results demonstrate that HP‐β‐CD, HE‐β‐CD, and Me‐β‐CD have stronger recognition abilities for S‐α‐CHMA than for R‐α‐CHMA. Among the three derivatives, HP‐β‐CD shows the strongest separation factor for α‐CHMA enantiomers. A high enantioseparation efficiency with a maximum separation factor (α) of 2.02 is observed at pH 2.5 and 5°C.     

Base‐Induced Decarboxylation of Polyunsaturated α‐Cyano Acids Derived from Malonic Acid: Synthesis of Sesquiterpene Nitriles and Aldehydes with β‐, φ‐, and ψ‐End Groups

Catalytic base‐induced decarboxylation of polyunsaturated α‐cyano‐β‐methyl acids derived from malonic acid led to the corresponding nitriles 3 (Schemes 2 and 3), 6 (Scheme 5), and 9 (Scheme 6). This decarboxylation occurred with previous deconjugation of the α,β‐alkene moiety of the α‐cyano‐β‐methyl acid, leading to an α‐cyano‐β‐methylene propanoic acid which was easily decarboxylated (see Scheme 2). β‐Methylene intermediates, in some cases, could be isolated; mechanistic pathways are proposed. The nitriles 3, 6 , and 9 were reduced to the sesquiterpene aldehydes 4 (β‐end group), 7 (φ‐end group), and 10 (ψ‐end group), respectively.     

Complete 1H NMR assignments of pyrrolizidine alkaloids and a new eudesmanoid from Senecio polypodioides

Chemical investigation of the aerial parts of Senecio polypodioides lead to the isolation of the new eudesmanoid 1β‐angeloyloxyeudesm‐7‐ene‐4β,9α‐diol ( 1 ) and the known dirhamnosyl flavonoid lespidin ( 3 ), while from roots, the known 7β‐angeloyloxy‐1‐methylene‐8α‐pyrrolizidine ( 5 ) and sarracine N‐oxide ( 6 ), as well as the new neosarracine N‐oxide ( 8 ), were obtained. The structure of 1 and 8 was elucidated by spectral means. Complete assignments of the ¹H NMR data for 5 , 6 , sarracine ( 7 ), and 8 were made using one‐dimensional and two‐dimensional NMR experiments and by application of the iterative full spin analysis of the PERCH NMR software. Copyright © 2014 John Wiley & Sons, Ltd.     

Catalytic Hydrogenation of α,β-Epoxyketones to β-Hydroxyketones with Two Sulfinyl Analogues of Coenzyme NADH Models

An efficient method for the selective hydrogenation of a series of α,β-epoxyketones to β-hydroxyketones using catalytic amount of two sulfinyl analogues of NAD^＋ model compounds is reported. The lack of any diastereoselectivity for the formation of β-hydroxyketones with optically pure sulfinyl analogue of NAD^＋ model supports the radical mechanism proposed previously.     

Synthesis and Pharmacological Evaluation of Some Novel Imidazo[2,1-b][1,3,4]thiadiazole Derivatives

Synthesis of bis‐1,3‐{6′‐arylimidazo[2,1‐b][1,3,4]thiadiazol‐2‐yl}‐1,2,2‐trimethylcyclopentane ( 3 ), bis‐1,3‐{thiadiazolo[2′,3′:2,1]imidazo[4,5‐b]quinoxalinyl}‐1,2,2‐trimethylcyclopentane ( 5 ) has been achieved by the reaction of bis‐(5′‐amino‐1′,3′,4′‐thiadiazolyl)‐1,2,2‐trimethylcyclopentane with α‐haloketones, 2,3‐dichloroquinoxaline respectively. Bromination of compound 3 furnished bis‐1,3‐{5′‐bromo‐6′‐arylimidazo[2,1‐b][1,3,4]thiadiazol‐2‐yl}‐1,2,2‐trimethylcyclopentane ( 4 ). The structural assignment of these compounds was supported by IR, ¹H NMR and elemental analysis data. The antimicrobial, anti‐inflammatory and antifungal activities of some of the compounds have also been evaluated.