Asymmetric Synthesis of （-）-（4R, 5R）-4-[5-（Benzo[1, 3]dioxol-5-yl）-4- hydroxyl- 1-（pyridin-2-yl）-4, 5-dihydro- 1H-pyrazol-3-yl]benzamide

For discovering novel small molecule inhibitors of transforming growth factor-β1(TGF-β1)type-I receptor(ALK5),we designed1,3,5-triaryl-4-hydroxyl-4,5-dihydro-1H-pyrazole(1)as target compound,mimic the structure of SB-431542which is a2-pyridyl substituted triarylimiazole inhibitor of ALK51.Racemic compound1showed moderate ALK5inhibitory activity in luciferase reporter assays[inhibition(%control):0.1umol/L8.79%;1umol/L19.05%].To investigate the influence of the absolute configuration of…     

A Convenient Approach to the Enantiopure （1S, 2S, 4S, 5S ）- and（ 1R, 2S, 4R, 5 S ）-2,5-Bis （ phenylmethyl）-l, 4-diazabicyclo[ 2.2.2 ] -octane

Cyclodipepflde (3S, 6S )-bis (phenylmethyl) piperazlne-2,5-dione was prelmred in high yield by heating phenylalanine methyl ester in toluene under reflux. The reduction of this cydodipeptide with sodium NaBH4-BF3 in DIME gave the (2S ,SS)-bis(phenyl-methyl)plperazine, which, on heating with ethylene bromide and triethyiamine, afforded the title compounds. This methodwas proved to be generally applicable to the synthesis of C2-symmetric 2, 5-disubsiituted=l, 4-diazabicyclo [ 2.2.2 ] octanefrom the corresponding natural or unnatural amino acid esters.     

Synthesis and Crystal Structure of 5（R）-（1R,2S,5R）-Menthoxy-4（R）- N-cyclohexylaminobutyrolactone

1INTRODUCTION Substitutedγ-butyrolactones are a group of impor-tant compounds containing unique carbon skeleton of butyrolactone which is widely present in many natural products and have received considerable interest because of their biological and medicinal properties[1～4].Therefore,much attention has been paid to the new asymmetric methods for synthesi-zing these interesting compounds[5～11].The prece-ding results led us to explore the possibility of using cyclohexylamine to convert5(…     

Synthesis and Crystal Structure of Ethyl 5-Amino-1-[（5′-methyl-1′- t-butyl-4′-pyrazolyl）carbonyl]-3-methylthio-1H-pyrazole-4-carboxylate

1INTRODUCTIONPolarizedketenedithioacetalshavebeenex-tensivelyusedasbuildingblocksinorganicsyn-thesis,especiallyinthesynthesisofheterocycliccompounds[1～6].Pyrazoleanditsderivativesrepre-sentoneofthemostactiveclassesofcompoundspossessingwidespectraofbiologicalactivities.Overthepastfewyears,considerableevidenceshavebeenaccumulatedtodemonstratetheefficacyofpyrazolederivatives,suchasantibacterial[7],fun-gicidal[8],herbicidal[9],insecticidal[10]andotherbiologicalactivities[11,12].Uptonow,alarg…     

Convenient synthesis of （2S,3R,4R,5S,6R）-2-（3-（4-ethylbenzyl）-4- chlorophenyl）-6-（hydroxymethyl）-tetrahydro- 2H-pyran-3,4,5-triol

A convenient approach for the preparation of （2S,3R,4R,5S,6R）-2-（3-（4-ethylbenzyl）-4-chlorophenyl）-6-（hydroxymethyl）- tetrahydro-2H-pyran-3,4,5-triol I is developed. The target compound via four steps is synthesized from 4-bromo-2-（bromomethyl）- 1-chlorobenzene and the isomers of undesired ortho-products were avoided during the preparation.     

Synthesis and Crystal Structure of N-[（3aR,4R,4aR,5aS,6S,6aS）-1,3-Dioxooctahydro-4,6-ethenocyclopropa[f]isoindol-2（1H）-yl]-3-（trifluoromethyl）phenylmethanimine

The crystal structure of the title compound(C19H15F3N2O2,Mr = 360.33) was determined by single-crystal X-ray diffraction.The crystal belongs to triclinic,space group P1,with a = 6.5604(7),b = 13.9614(16),c = 18.1790(18) ,α = 102.749(7),β = 97.542(6),γ = 94.355(4)°,V = 1600.5(3) 3,Z = 4,Dc = 1.495 g/cm3,λ(MoKα) = 0.71070,F(000) = 744,μ(MoKα) = 0.122 mm-1,R = 0.0434 and wR = 0.1051.A total of 7590 unique reflections were collected,of which 5429 with |F|2 ≥ 2σ|F|2 were observed.The two cyclohexene rings in the molecule adopt boat-boat conformations with the deviations of ring atoms C(9) and C10 from the C(5)/C(6)/C(7)/C(8) plane(Ⅰ) by 1.1204(0.0023) and 1.1132(0.0023) ,respectively,whereas from the C(2)/C(3)/C(5)/C(8) plane(Ⅱ) by 1.1627(0.0022) and 1.1818(0.0021) ,respectively.In the cyclopropane and lactam rings,atoms C(11) and N(1) point towards the double bond of C(9)-C(10) and the dihedral angle between the ring plane(Ⅲ) containing C(1),C(2),C(3) and C(4) and plane(IV) consisting of C(6),C(7) and C(11) is 55.76(0.07)°.The dihedral angles between planes Ⅳ and Ⅰ and Ⅱ and Ⅲare 63.58(0.07)° and 58.10(0.06)°,respectively.The dihedral angle between the benzene ring C(13)～ C(18) and plane Ⅳ is 42.41(0.06)°.     

棒丝氨酸的全合成研究 Ⅰ.从D-葡萄糖合成3-[(3′R,5′S)-7′-氧代-1′-氮杂-4′-氧杂双环[3.2.0]-庚-3′-基]-3-O-苄基-(2S,3S)-丝氨酸及其(3′R,5′R)-差向异构体

以D-葡萄糖为原料经侧链氨基酸合成,与β-内酰胺缩合,嗯唑烷环合和除保护基等反应合成了棒丝氨酸的O-苄基衍生物,3-[(3′R,5′S)-7′-氧代-1-氮杂-4-氧杂双环[3.2.0]-庚-3′-基]-3-O-苄基-(2S,3S)-丝氨酸(17)及其(3′R,5′R)差向异构体(18)。     

手性5-(R)-(1′R,2′S,5′R)-孟氧基丁内酯并[3,4-b]-2(S)-6(R)-1-N-环己基氮杂环丙烷的合成及晶体结构

环己胺与手性元5-(R)-(1′R,2′S,5′R)-孟氧基-3-溴-2(5H)-呋喃酮的不对称M ichael加成/分子内亲核取代反应,得到含有两个新手性中心的氮杂环丙烷/稠合丁内酯标题化合物。对其进行了谱学表征和X-射线单晶衍射测定。标题化合物分子式为C20H33NO3,M r=335.47,三斜晶系,P1空间群,晶胞参数:a=5.438(11)。A,b=8.117(2)。A,c=11.572(2)。A,α=96.84(3)°,β=94.48(3)°,γ=101.86(3),°V=493.5(2)。A3,Z=1,D c=1.129g/cm3,R=0.0867,wR=0.2344。     

Synthesis of Quinolone Analogues： 7-[（2S, 4R）-2-Aminomethyl-4- hydroxypyrrolidin-l-yl] Quinolones

New quinolone derivatives of 7-[(2S, 4R)-2-aminomethyl-4-hydroxypyrrolidin-l-yl] quinolone-3-carboxylic acids were synthesized by condensation of 7-halo substituted quinolone-3-carboxylic acids with (2S, 4R)-2-aminomethyl-4-hydroxypyrrolidine. These compounds were characterized by FAB-MS and IH NMR.     

A Convenient Approach to the Enantiopure (1S,2S,4S,5S)-and (1R,2S,4R,5S)-2,5-Bis(phenylmethyl)-1,4-diazabicyclo[2.2.2]-octane

Introduction1,4 Diazabicyclo[2 .2 .2 ]octane (DABCO)wasre portedtocatalyzeorganicreactionsduetoitsstrongbasici ty .1,2 Severalchiraltrans 2 ,3 disubstitutedDABCOshavebeensynthesizedandappliedtotheasymmetricBaylis Hillmanreaction3andvicinalhydroxylation .4ThefirstsynthesisofthetitlecompoundwasreportedbySoai5from (2S ,5S) bis(phenylmethyl)piperazine (1) ,asshowninScheme 1.Butthisprocedureislengthy ,andtheoverallyieldisnotsosatisfactory .Besides ,thereport edmethodforthepreparationof 1is…     

Synthesis and Crystal Structure of Spiro[1-bromo-4-methoxy-5-oxa-6-oxo-bicyclo[3.1.0]hexane-2,2′-（3′- cyclohexanoxy-4′-methoxybutyrolactone]

1INTRODUCTIONThecyclopropane-containingnaturalproductshavereceivedconsiderableattentionassynthetictar-getsastheincorporationofrigidifiedcyclopropylmotifintobioactiveanaloguescanleadtoconfor-mablyconstrainedmolecules[1,.Suchmodifica-2]tionsareexpectedtohavesignificanteffectsonbio-activitieswithconcomitantmedicalimplications.Des-pitethegreatadvancesinthisfield,theefficientsyn-thesisofspiro-cyclopropanecompoundsstillremainsaconsiderablechallenge.Particularnoticeisthede-ficiencyinthepreviousm…     

(1R,4S,5S)-6-环己基-4-[(1R,2S,5R)-5-甲基-2-异丙基环己氧基]-3-氧杂-6-氮杂双环[3.1.0]-2-己酮的合成及结构表征

环已胺与差向异构体5-[(1R,2S,5R)-5-甲基-2-异丙基环己氧基]-3-溴-2(5H)-呋喃酮发生不对称Mi-chael加成-分子内亲核取代反应,并经柱层析分离,得到一对手性氮杂环丙烷-丁内酯衍生物,其中的标题化合物为首次得到的新手性化合物,产率17%,其结构经IR、1H NMR、13C NMR和HRMS进行了表征。     

（E）-1-[4-（2-hydroxy-5-methoxybenzylideneamino）-phenyl]ethanone and （E）-1-[4-（2-hydroxy-4-methoxybenzylideneamino） phenyl]ethanone：X-ray and DFT-calculated structures

The isomeric structures of(E)-1-[4-(2-hydroxy-5-methoxybenzylideneamino)-phenyl] ethanone(I) and(E)-1-[4-(2-hydroxy-4-methoxybenzylideneamino) phenyl]ethanone(Ⅱ) ,both C16H15NO3,have been determined using X-ray diffraction techniques and characterized by IR,and their molecular structures have also been optimized at the B3LYP/6-31G(d,p) level using density functional theory(DFT) . The energetic behaviors of the title compounds in solvent media have been examined using B3LYP method with the 6-31G(d,p) basis set by applying the polarizable continuum model(PCM) . The total energies of the title compounds decrease with the increasing polarity of the solvent. In addition,DFT calculations of the title compounds' molecular electrostatic potentials(MEP) were performed at the B3LYP/6-31G(d,p) level of theory. X-ray study shows that the title compounds both have strong intramolecular O-H…N hydrogen bonds. The molecules of Ⅰ are linked into a one-dimensional framework structure by C-H…π interactions,while in Ⅱ,intermolecular π···π interactions result in the formation of infinite chains running along the [010].     

Crystal Structure and Biological Activities of （R）-N′-[2-（4-Methoxy-6-chloro）-pyrimidinyl]- N-[3-methyl-2-（4-chlorophenyl）butyryl]-urea

1 INTRODUCTION The acyl ureas are a kind of high biological acti- vity compounds with low toxicity to mammals, birds, fish, amphibians, etc., and significant organic synthe- sis intermediates working extensively as insecticides, pesticides, fungicides and herbicides in agrochemi- cal industry[1～7]. While pyrimidinyl derivatives show excellent biological activities in the development of pesticide, and are used to develop high effective and high select herbicides. For example, pyrimidiny su…     

One-pot Synthesis and Crystal Structure of （1S,2R,3S,4R,5S）-1-Phenyl-2,4-dibenzoyl-3,5-difurylhexanol

(1S,2R,3S,4R,5S)-1-Phenyl-2,4-dibenzoyl-3,5-difurylhexanol 1 was synthesized by one-pot reaction of hypnone and furfurol in alkali H2O/EtOH solution and structurally defined to contain a chair-formed aliphatic carbocycle, on which the bulky substituents occupy the equatorial positions.     

Crystal Structure of Phenol,2-[4（S）-4-Dihydro-4-benzyl-2-ozazolinyl]

The compound phenol,2-[4(S)-4,5-dihydro-4-phenyl-2-ozazolinyl(1,C15H13NO2) was synthesized with a simple,one step method free of water and air.It was obtained in a moderate yield from the reaction of 2-hydroxybenzonitrile with optically active amino alcohol in chloroben-zene under dry,anaerobic conditions.It belongs to the orthorhombic system,space group P212121 with a = 5.786(5),b = 10.730(5),c = 19.722(5),C15H13NO2,Mr = 239.26,V = 1224.4(12)3,Z = 4 and Dc = 1.298 mg/m3.The final R = 0.0324 for 1627 observed reflections with Ⅰ 2σ(Ⅰ) and Rw = 0.0826 for all data.The structure of compound 1 was determined by X-ray diffraction,NMR and HRMS.