Synthesis and antibacterial activity of C-2(S)-substituted pleuromutilin derivatives

In order to probe the effect of C-2(S)-substituted groups in the antibacterial activity,a series of novel C-2(S)-substituted pleuromutilin analogues of SB-225586 were synthesized and evaluated for their in vitro antibacterial activity.The results of antibacterial activities indicated that C-2(S)-substituted pleuromutilin derivatives retained appreciable antibacterial activity,and the 2-fluorination compounds 6a and 6b are more potent than the corresponding 2-hydroxylation analogues 7a and 7b.

A simple and efficient synthesis of 2-substituted benzothiazoles catalyzed by H_2O_2/HCl

A simple and efficient procedure for the synthesis of substituted benzothiazoles through condensation of 2-aminothiophenol with aromatic aldehydes in the presence of H2O2/HCl system in ethanol at room temperature is described. The target compounds have been characterized by ^1H NMR, ^13C NMR, IR and MS. Short reaction time, easy and quick isolation of the products, and excellent yields are the main advantages of this procedure.

Synthesis and anti-HBV activity of novel 5-substituted pyridin-2(1H)-one derivatives

Four novel 5-substituted pyridine-2(1H)-one derivatives were designed and synthesized by using addition-elimination reactions.The structures of these novelly synthesized compounds were verified by ~1H NMR,ESI-MS and single crystal X-ray diffraction.Furthermore,all four compounds(most notably compound 7a) were found to be highly efficient against hepatitis B virus (HBV) in cultured HepG2 2.2.15 cell,making them promising drug candidates for potential bioactive molecule against hepatitis B.

Ga(ClO_4)_3-catalyzed Reaction of 1,2-Diamines and α-Bromoketones:Synthesis of 2-Substituted Quinoxalines

Ga（ClO4）3-catalyzed reaction of 1,2-aryldiamines and α-bromoketones to afford 2-substituted quinoxalines in good yields is described.The reaction proceeded via grinding process with 10%（molar fraction） catalyst under solvent-free conditions at room temperature.For unsymmetrical o-phenylenediamines bearing electron-withdrawing groups,regio-selective quinoxalines were obtained.

Synthesis of 2-Phenyl-10-substituted Hymenialdisine Derivatives

A series of novel 2-phenyl-10-substituted hymenialdisine derivatives was synthesized via the micro-wave-assisted Suzuki-Miyaura cross-coupling reactions of the 2-phenyl derivative of hymenialdisine and boronic acid, which enabled the successful introduction of electron-donating and electron-withdrawing groups to the 2-phenyl- hymenialdisine derivatives in good yields.

Syntheses of 2- or 6-Substituted Chromones and Chromone Ring-opening Reaction in Polyphosphoric Acid

In an attempt to find new antitumor agents,a novel class of chromone compounds with a benzimidazole or a benzoxazole ring in positions 2 or 6 were synthesized via condensation in polyphosphoric acid(PPA) by using chromone acids as the starting materials. During the preparation process,it was found that PPA could cleave the chromone ring to produce a ring-opening compound(6). The molar ratio of the chromone compound(5) to the ring-opening compound(6) varied with the change of reaction temperature and time. Based on MTT protocol,the antitumor activity of each of the compounds obtained was evaluated against three human cancer cell lines: KB(oral epidermal),A2780(ovary) and Bel7402(liver). The IC_ 50 varied from 54.7 μmol/L to more than 180 μmol/L.

SYNTHESIS OF 4-SUBSTITUTED (OR 4-SPIRO) 3-OXABICYCLO[3.1.0]HEXAN-2-ONE

Cyclopropanedicarboxylic anhydride can be converted to 4-substituted (or 4-spiro-)3-oxabicyclo[3.1.0]hexan-2-one by addition of Grignard (or α,ω-di-Crignard) reagents in ether or tetrahydrofuran solution.

3-(N-四氢吡咯)-2-羟基丙磺酸的合成研究

目的 :合成一种应用于生物反应体系的新型缓冲剂。方法 :以四氢吡咯、3-氯 - 1,2 -环氧丙烷、亚硫酸氢钠为原料 ,通过一种氢型的阳离子交换树脂合成 3- (N-四氢吡咯 ) - 2 -羟基丙磺酸。结果 :产物经熔点、HRMS、1 H NMR、1 3C NMR等方法鉴定。结论 :该产物适用于生物体系研究 。

2-取代四氢吡咯的结构与旋光方向的关系

由于2取代四氢吡咯结构的信封式和扭曲式能差很小,在平衡体系中共存,2位上的取代基处于e键和a键的能差也较小,所以平衡体系是10种信封式和10种扭曲式构象的平衡混合物。每种构象都包括特有的数种螺旋,很难推断其旋光方向。为了将旋光方向与其构型联系在一起,假设平衡体系所有构象中环原子的平均构象位置处于同一平面中。按照平面式中存在的螺旋,利用螺旋理论可以估算2取代四氢吡咯的旋光方向,对于各种不同类型的这类化合物,都能准确地将化合物的构型和旋光方向联系在一起。和其它化合物一样,通过构型可以预测其旋光方向;通过旋光方向可以推断其C(2)的绝对构型。

Stereo-Selective Synthesis of 5-Norbornene-2-<i>exo</i>-carboxylic Acid—Rapid Isomerization and Kinetically Selective Hydrolysis

Simple and efficient stereo-selective synthesis of exo-5-norbornene-2-carboxylic acid (NBCA) is reported. Preliminary studies on base promoted isomerization of methyl 5-norbornene-2-carboxylate (MNBC) revealed that rapid isomerization was accomplished with sodium tert-butoxide (tBuONa), and the exo-content at the equilibrium was ca. 60%. The hydrolyses of endo-rich MNBC (endo/exo = 80/20) under various conditions were carried out. The exo selectivity for resulting NBCA was improved when the hydrolysis was conducted with equimolar water at room temperature in the presence of the stronger base (tBuONa) (endo/exo: 18/82). Whereas the use of excess amount of water led to rapid and non-selective hydrolysis affording high endo content of the product. The plausible reaction mechanism involving rapid equilibrium of thermodynamic isomerization and kinetically preferred hydrolysis of exo ester is proposed.

Synthesis and Conformation Analysis of cis-1,2-Disubstituted Cyclododecanes

cis-1,2-Disubstituted cyclododecanes 2 were synthesized by sodium borohydride reduction of 2-monosubstituted cyclododecanones and their structures were confirmed by 1HNMR, ^13C NMR and elemental analysis. The higher cis-selectivity of NaBH4 reduction of 2- monosubstituted cyclododecanones was rationalized by the mode of ＂corner position carbonyl participation＂. Crystal data for 2c： Mr = 263.21, monoclinic, space group P21/c, a = 1.11140（7）, b = 2.62590（17）, c = 0.91360（6） nm, β= 106.1840（10）°, V = 2.5606（3） nm^3, Dc = 1.366 g/cm^3, Z = 8, F（000） = 1104, μ（MoKα= 3.182 mm^-1, S = 0.837, the final R = 0.0460 and wR = 0.1033. Crystal X-ray diffraction analysis for 2c showed that its ring skeleton adopts [3333] conformation, in which the OH group presents at the side-exo position and the other one at the corner carbon. The 1H NMR data of 2 showed that 1-corner-R-2-side-exo-OH [3333] and 1-corner-OH-2-side-exo-R [3333] conformations coexist in dynamic equilibrium in the solution, but only the former presents in the crystal.

An Efficient Synthesis of 2-Substituted Benzoxazoles via RuCl3.3H2O Catalyzed Tandem Reactions in Ionic Liquid

An efficient synthesis of 2-substituted benzoxazoles through RuCl3·3H2O catalyzed, air oxidized tandem reactions of 2-aminophenols and aldehydes in [bmim]BF4 was developed. This synthetic strategy has such advantages as mild reaction conditions, cost-free oxidant, readily available starting materials, and recyclable catalyst and solvent. As an application, it was successfully used in the synthesis of the unreported 5-（benzoxazol-2-yl）-2＇-deoxyuridines with potential biological activities.

An effcient one-pot multi-component synthesis of 3,4,5-substituted furan-2(5H)-ones catalyzed by tetra-n-butylammonium bisulfate

A facile one-pot synthesis of 3,4,5-substituted furan-2（5H）-one derivatives from a three-component reaction of aniline derivatives, dialkylacetylenedicarboxylates and aromatic aldehydes under mild conditions using tetra-n-butylammonium bisulfate as a catalyst has been developed.

[4+1]Annulation of in situ generated azoalkenes with amines:A powerful approach to access 1-substituted 1,2,3-triazoles

1-Substituted 1,2,3-triazoles represents‘privileged’structural scaffolds of many clinical pharmaceuticals.However,the traditional methods for their preparation mainly rely on thermal[3+2]cycloaddition of potentially dangerous acetylene and azides.Here we report a base-mediated[4+1]annulation of azoalkenes generated in situ from readily available difluoroacetaldehyde N-tosylhydrazones(DFHZ-Ts)with amines under relatively mild conditions.This azide-and acetylene-free strategy provides facile access to diverse 1-substituted 1,2,3-triazole derivatives in high yield in a regiospecific manner.This transformation has great functional group tolerance and can suit a broad substrate scope.Furthermore,the application of this novel methodology in the gram-scale synthesis of an antibiotic drug PH-027 and in the late-stage derivatization of several bioactive small molecules and clinical drugs demonstrated its generality,practicability and applicability.

Cu（I）-Catalyzed Synthesis of 2-Substituted Benzimidazoles from 2-lodoanilines and Amides

A novel and efficient approach to the synthesis of 2-substituted benzimidazoles has been developed via CuI/DMEDA-catalyzed coupling reaction and post-cyclization with glacial acetic acid from readily available 2-iodoanilines and amides. This method is suitable for the construction of a variety of benzimidazoles in moderate to good yields under short reaction times.

Asymmetric Hydrogenation of Tetrasubstituted α,β-Unsaturated Ketones:Access to Chiral 2-Substituted Cyclopentyl Aryl Ketones

Asymmetric hydrogenation of tetrasubstituted alkenes is an important but challenging research topic.Herein,we report an efficient iridium-catalyzed asymmetric hydrogenation of tetrasubstituted α,β-unsaturated ketones for the synthesis of chiral 2-substituted cyclopentyl aryl ketones,an important chiral structural motif for the preparation of chiral pharmaceuticals and bioactive molecules.The reaction proceeded very well with good functional group compatibility and delivered the hydrogenated products in high yields and stereoselectivities(up to 99% yield,>20:1 dr and 99%ee).In addition,the reaction could be carried out on a gram-scale,and all four stereoisomers of the hydrogenated products bearing two contiguous stereocenters were obtained.Furthermore,the hydrogenated product can be transformed into the ERβ agonist Erteberel,and the reaction pathway was also studied via deuterium-labelling experiments.

Synthesis of 4-substituted 3-oxabicyclo[3.1.0]hexan-2-one

Cyclopropanedicarboxylic acid anhydride can be converted to 4-substituted 3-oxabicyclo- [3.1.0]hexan-2-one by reaction with Grignard reagents in ether or tetrahydrofuran solution.

Synthesis of Schiff Base Calix[4]arene Crowns

This letter reports the synthesis of Schiff base calix[4]arene crowns containing m-xylylene phenol subunit, in which calix[4]arene Schiff base crowns 2a, 2b and 2c were formed by 1:1 condensation of calix[4]arene diamine 1 with dialdehydes (2, 6-diformyl-4-chlorophenol 3a, 2, 6-diformyl-4-methylphenol 3b, 2, 6-diformyl-4-tert-butylphenol 3c) under high dilute condition in refluxing anhydrous ethanol in 65-70% yield.

Glycerol mediated synthesis of 5-substituted lH-tetrazole under catalyst free conditions

We have developed simple,cost effective and environmentally benign protocol for the synthesis of 5-substituted 1H-tetrazoles via[2,3]cycloaddition reaction from organic nitriles and sodium azide in glycerol under catalyst free condition.The corresponding 5-substituted 1H-tetrazoles were obtained with good to excellent yields（68-95%）.