An Unusual Occurrence in the Reaction of 4-Azasteroid Derivatives with N-Fluorodibenzenesulfonimide and Lithium Diisopropylamide

The reaction of N,N-diethyl-3-oxo-4-methyl-4-aza-5-androstane-17β-carboxamide(1) with N-fluorodibenzenesulfonimide(NFA) and lithium diisopropylamide(LDA) was studied.Under absolute anhydrous and anaerobic conditions,the formation of 5(2α-fluoro-4-methyl-3-oxo-4-aza-5α-androstane-17β-carboxylic acid methyl ester) can be rationalized by participating in the expected nucleophilic substitution reaction.Not in absolute anhydrous and anaerobic conditions,the formation of 10(N-di-isopropyl-N'-aryl-sulfonamides(C12H20N2O2S) and 11(N-diethyl-3-oxo-4-methyl-4-aza-5-androstene-17β-carboxamide) can be rationalized by assuming that the situ genera-ted carbanion 2 followed by a single electron transfer mechanism.5,10 and 11 were characterized.10 was a new compound and determined by X-ray single-crystal diffraction.Crystal data for 10:space group C2/c with a = 14.783(2),b = 7.6193(11),c = 24.663(3) ,β = 98.688(3)o,V = 2746.1(7) nm3,Mr = 256.36,Z = 8,Dc = 1.240 g/cm3,μ = 0.229 mm-1,F(000) = 1104,R = 0.0511 and wR = 0.1268.There exist intramolecular H-bonds which result in a supramolecular framework of the title compound.The formation mechanisms of 10 and 11 were also discussed briefly.     

Synthesis and Crystal Structure of 2-Methoxy-benzoic Acid 2-Oxo-3-（2,4,6-trimethyl-phenyl）-1-oxa-spiro[4.4]non-3-en-4-yl Ester

The new title compound 2-methoxy-benzoic acid 2-oxo-3-(2,4,6-trimethyl-phenyl)-1-oxa-spiro[4.4]non-3-en-4-yl ester(3,C25H26O5) has been synthesized by the condensation reaction of 4-hydroxy-3-(2,4,6-trimethyl-phenyl)-1-oxa-spiro[4.4]non-3-en-2-one(2) with 2-methoxylben-zoyl chloride,and characterized by 1H NMR and MS spectra.Its crystal structure was determined by single-crystal X-ray diffraction.The crystal is of monoclinic,space group P21/c with a = 10.6945(7),b = 12.8176(7),c = 16.4223(10) ,β = 103.5665(17)o,V = 2188.3(2) 3,Z = 4,Dc = 1.234 g/cm3,F(000) = 864.000,μ = 0.085 mm-1,the final R = 0.0520 and wR = 0.1132 for 2732 observed reflections with I 2σ(I).In the crystal structure,the C(1)-C(2)(1.478 ) bond is significantly shorter than the normal single C-C bond(1.53 ),suggesting that the carbonyl group on C(1) has formed a conjugated system with a double bond on C(2) and C(12).     

Synthesis,Crystal Structure and Anti-tumor Activity of Ethyl 3-（4-methoxyphenyl）-4-oxo-3,3a,4,6-tetrahydro-1H-furo[3,4-c]pyran-3a-carboxylate

The title compound(ethyl 3-(4-methoxyphenyl)-4-oxo-3,3a,4,6-tetrahydro-1H-furo[3,4-c]pyran-3a-carboxylate) has been synthesized,and its crystal structure was characterized by X-ray single-crystal diffraction.The crystal belongs to monoclinic,space group P21/n,with a = 10.124(4),b = 11.754(4),c = 13.792(5) ,β = 111.533(3)o,V = 1526.6(10) 3,Z = 4,C17H19O6,Mr = 319.32,Dc = 1.389 g/cm3,F(000) = 676,λ(MoKα) = 0.71073 ,μ = 0.105 mm-1,R = 0.0660 and wR = 0.2027 for 2993 observed reflections(I > 2σ(I)).The compound shows potent anti-tumor activity in vitro.     

Synthesis,Crystal Structure and Biological Activity of N-tert-butyl-N-(4-methyl-1,2,3-thiadiazole)-5-yl-N’-(4-methyl-1,2,3-thiadiazole)-5-formyl-N’-3,5-dichloropyridin-2-yl-diacylhydrazine

The title compound N-tert-butyl-N-(4-methyl-1,2,3-thiadiazole)-5-yl-N'-(4-me-thyl-1,2,3-thiadiazole)-5-formyl-N'-3,5-dichloropyrid-2-yl-diacylhydrazines (C18H17Cl2N7O3S2, Mr = 514.41) has been synthesized by the reaction of N-tert-butyl-N'-3,6-dichloropyridine-2-formyl hydrazine with 4-methyl-1,2,3-thiadiazole-5-carbonyl chloride and triethylamine, and its structure was characterized by 1H NMR, HR MS, and single-crystal X-ray diffraction. The crystal of the title compound belongs to monoclinic, space group C2/c with a = 27.726(8), b = 11.045(3), c = 14.507(4), β = 96.758(4)°, Z = 8, V = 4412(2) 3, Dc = 1.549 g/cm3, μ = 0.521 mm-1, F(000) = 2112, R = 0.0405 and wR = 0.1153. X-ray analysis indicates that all rings are non-planar in this molecule. The bioassay results indicate that both the title compound and the positive control RH-5992 have weak fungicide activities, while the title compound has good insecticidal activity against Plutella xylostella L. and no insecticidal activity against Culex pipiens pallens.     

Synthesis,Crystal Structure and DNA Binding Studies of α,α'-Bis(3,5-bismethyl-1-pyrozolyl)-carbene-acetyl-isopropenyl Hydrazine

The title compound α,α'-bis(3,5-bismethyl-pyrozole-N-yl)-carbene-acetyl-isopro- penyl hydrazine (C16H22N6O, Mr = 314.40) has been prepared. It was characterized by elemental analysis as well as IR, MS, 1H-NMR and 13C-NMR spectra. Its crystal structure was determined by single-crystal X-ray diffraction, getting the following data: triclinic, space group P1 with a = 6.9734(16), b = 10.773(3), c = 12.001(3) , α = 75.311(4), β = 82.695(4), γ = 77.143(4)o, Z = 2, V = 847.9(3) 3, Dc = 1.231 g/cm3, F(000) = 336 and μ(MoKα) = 0.082 mm-1 (λ = 0.71073 ). The results of crystal structure determination show that there exist intermolecular and intramolecular hydrogen bonds, resulting in a two-dimensional supramolecular framework of the title compound. The binding of the title compound to DNA was investigated by absorption, emission, and viscosity measurements. The title compound shows absorption hyperchromicity accompanied by a blue shift at about 254 nm. The binding constant Kb for the title compound has been determined to be 1.89 × 104 M-1 from absorption measurements. The addition of the title compound to DNA pretreated with EB causes appreciable reduction in the emission intensity, indicating that the DNA-bound EB fluorophore is partially replaced by the title compound. The value of K is 3.093 × 104 M-1. The relative viscosity of DNA decreased with the addition of the title compound. Results suggest that the title compound binds to DNA with a non-classical intercalative or groove interaction mode. The observed efficient nuclease activity of the title compound is interesting and may have further influences on the chemistry of DNA minor groove binders. Keywords: α,α'-bis(3,5-bismethyl-pyrozole-N-yl)-carbene-acetyl-isopropenyl, preparation, crystal structure, DNA binding     

Synthesis and Crystal Structure of 3′-Ethyl 5′-Methyl 1-Benzyl-4′-methyl-2-oxo-3′,4′-dihydrospiro-[indoline-3,2′-pyrrole]-3′,5′-dicarboxylate

The crystal structure of the title compound(C24H24N2O5, Mr = 420.45) has been determined by single-crystal X-ray diffraction. The crystal is of triclinic, space group P1 with a = 8.991(1), b = 11.166(1), c = 11.169(1) , α = 91.413(2), β = 105.887(2), γ = 90.992(2)°, V = 1077.8(2) 3, Z = 2, Dc = 1.296 g/cm3, F(000) = 444, μ(MoKα) = 0.091 mm-1, the final R = 0.0466 and wR = 0.1507 for 4185 observed reflections(I 2σ(I)). The single-crystal X-ray diffraction data indicated intermolecular C(17)–H(17)O(4), C(5)–H(5)… O(4) hydrogen bonds and C–H…π interaction in the structure.     

Synthesis and Crystal Structure of N,N'-Bis-[(1-phenyl-3-methyl-5-oxo-4-pyrazolinyl)-α-furylmethylidyne]ethylenediimine

A new compound,N,N'-bis[(1-phenyl-3-methyl-5-oxo-4-pyrazolinyl)-α-furylme-thylidyne]ethylenediimine ((HPMαFP)2en),has been synthesized and characterized by IR spectra,thermogravimetric analysis and single-crystal X-ray diffraction. The title compound crystallizes in a monoclinic system,space group P21/c with a = 10.7485(11),b = 7.6972(8),c = 16.8367(18) ,β = 93.937(2)o,Z = 2,V = 1389.7(3) 3,Dc = 1.340 g/cm3,F(000) = 588.0,μ = 0.091 and S = 1.016. Structural analysis indicates that (HPMαFP)2en exists in an amine-one form. The molecules are well ordered through two intramolecular (N(3)-H(3)···O(1) and C(2)-H(2)···O(1)) and one intermolecular C(3)-H(3)···O(1) hydrogen bonds,leading to the formation of 1D infinite chains. The interactions of these hydrogen bonds contribute to the stabilization of the compound.     

Synthesis and Crystal Structure of 4-（4-Bromophenyl）- 3,4-dihydro-6-methyl quinolin-2（1H）-one

The title compound (C16H14BrNO) has been synthesized by the reaction of p-tolylamine, Meldrum’s acid and 4-bromo-benzaldehyde, and its structure was characterized by IR, 1H NMR and X-ray single-crystal diffraction. The crystal belongs to monoclinic, space group P21/n with a = 7.6850(11), b = 8.3004(11), c = 21.301(3) , β = 95.110(2)°, V = 1353.4(3) 3, Mr = 316.19, Z = 4, Dc = 1.552 g/cm3, μ(MoKα) = 3.028 mm-1, F(000) = 640, the final R = 0.0345 and wR = 0.0768. X-ray analysis reveals that the atoms of C(1), C(2), C(3), C(4), C(5) and N(1) form a six-membered ring of boat conformation.     

Synthesis, Crystal Structure and Inhibition of N-2-Thiophenesulfonyl-α-L-phenylalanine Ethyl Ester on K562 Cell Proliferation

The title compound N-2-thiophenesulfonyl-α-L-phenylalanine ethyl ester has been synthesized. Complete assignments were achieved by IR, MS, 1H NMR and single-crystal X-ray diffraction analyses. Using MTT assay, the inhibitory rate of the title compound on K562 cells (chronic myeloid 1eukemic cells) was measured and the result of preliminary bioassay showed that the title compound possesses antiproliferation effects on K562 cells. In order to investigate the relationship between structure and activity of the target compound, we report its crystal structure and biological behavior in the present paper. Crystallographic data: C15H17NO4S2, Mr = 339.42, monoclinic, space group P21, flack = –0.15(12), a = 5.7916(10), b = 11.5078(19), c = 12.924(2) , β = 97.781(3)o, Z = 2, V = 853.4(2) 3, Dc = 1.321 g/cm3, F(000) = 356, –7≤h≤7, –10≤k≤14, –15≤l≤15, R = 0.0628, wR = 0.1540 and μ(MoKα) = 0.327 mm-1. The molecule comprises a benzene and a thiofuran rings, and the intramolecular N(1)–H(1A)…O(1) makes a five-membered ring of O(1)–C(6)–C(5)–N(1)–H(1A).     

Extraction and Absolute Crystal Structure of Stachyose

The title compound stachyose(C24H42O21),a biologicaly active tetrasaccharide,was characterized by X-ray diffraction analysis.It crystallizes in the orthorhombic system,space group P21212 with C24H42O21,a = 23.8760(3),b = 12.71028(12),c = 10.81279(11) ,V = 3281.36(6) 3,Z = 4,Dc = 1.511 g/cm3,Mr = 746.58,F(000) = 1576,and μ = 1.230 mm-1.The final R = 0.0666 and wR = 0.1797 for 6298 observed reflections(I 2σ(I)).The molecular crystal structure of stachyose shows absolute stereochemistry of β-D-fructofuranosyl α-D-galactopyranosyl-(1→6)-α-D-galactopyranosyl-(1→6)-α-D-glucopyranoside.The molecule is composed of two α-D-galactoses,one α-D-glucose,and one β-D-fructose and sequentially linked as α-Gal(1→6) α-Gal(1→6) α-Glc(1→2) β-Fru.The title compound is stacked into a 3D layer structure through hydrogen bonds.NMR spectra data are also assigned.In the crystal packing,X-ray analysis indicates that there are two intramolecular and eleven intermolecular hydrogen bonds in this compound.     

Synthesis and Crystal Structure of N-[（2S）-4-bromo-2-（L-menthyloxy）-5-oxo-2,5-dihydro-3-furyl]-L-leucine

Starting from(5S)-(L-menthyloxy)-3,4-dibromo-5H-furan-2-one and L-leucine,the title compound N-[(2S)-4-bromo-2-(L-menthyloxy)-5-oxo-2,5-dihydro-3-furyl]-L-leucine 5(C20H32BrNO5,Mr = 446.37) was obtained in one-pot process via the tandem Michael addition-elimination reaction in the presence of potassium hydroxide.The chemical structure and absolute configuration of the title compound were confirmed via rotation,UV-Vis,FT-IR,1H NMR,13C NMR,MS and elemental analysis,especially by the X-ray single-crystal diffraction.The crystal crystallizes in an orthorhombic system,space group P212121 with a = 12.5249(16),b = 19.005(3),c = 19.719(3) ,V = 4693.7(10) 3,Z = 8,Dc = 1.263 g/m3,μ = 1.778 mm-1,F(000) = 1872,the final R = 0.0617 and wR = 0.1576 for 3967 observed reflections(I > 2σ(I)).X-ray analysis reveals that the title compound has two independent molecules in the asymmetric part of the unit cell with the two five-membered furanones being almost planar.The essential part of the electron delocalization is concentrated in the N(1),C(3),C(1),C(37) and O(7) region and N(2),C(28),C(27),C(30) and O(4) region in the other molecule respectively,but does not take place at the expense of delocalization within the ester function.     

Synthesis, Dimeric Crystal Structure, and Biological Activities of N- （ 4-Methyl-6-oxo-1,6-dihydro-pyrimidin-2-yl ） -N＇- （ 2-trifluoromethyl-phenyl ） -guanidine

The title compound, N-（4-methyl-6-oxo-1,6-dihydro-pyrimidin-2-yl）-N＇-（2-tritluoromethyl-phenyl）-guanidine, was synthesized and its structure was confirmed by using IR, MS,^1H NMR, and elemental analysis. The single crystal structure of the title compound was determined by X-ray diffraction. The preliminary biological test showed that the synthesized compound has a weak herbicidal activity.     

Synthesis, Crystal Structure and Herbicidal Activity of O,O'-Diethyl-N-[2-(5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-yloxy)-benzoxyl]-1-amino-benzyl phosphonate

The crystal structure of the title compound (C25H28N5O5P,Mr= 509.49) has been determined by single-crystal X-ray diffraction. The crystal is of monoclinic, space group P21/c with a = 13.0726(4), b = 13.4513(4), c = 15.103(1) (A),β = 93.650(1)°, V= 2650.29(14) (A)3, Z= 4, Dc =1.277 g/cm3, F(000) = 1072, μ(MoKα) = 0.147 mm-1, the final R = 0.0748 and wR = 0.1956 for 3186 observed reflections (Ⅰ＞ 2σ(Ⅰ)). The fused triazolopyrimidine system ring is coplanar, the dihedral angles between the triazolopyrimidine and C(1)-C(3)-C(5) phenyl, the triazolopyrimidine and C(17)-C(19)-C(21) phenyl, and the two phenyl rings are 66.87, 58.79 and 80.11°, respectively.contribute to the stability of the structure and result in a three-dimensional framework. The preliminary bioassay indicates that the title compound exhibits moderate herbicidal activity against dicotyledonous plants (Brassica campestris L) at the concentration of 100 mg/L.     

Synthesis and Crystal Structure of 2-Ethoxycarbonylmethyl-8-chloro-3a,4-dihydro-3a-methyl-chromeno[4,3-c]pyrazol-3（2H）-one

The crystal structure of the title compound 2-ethoxycarbonylmethyl-8-chloro-3a,4-dihydro-3a-methyl-chromeno[4,3-c]pyrazol-3(2H)-one(C15H15ClN2O4,Mr = 322.74) has been prepared and determined by single-crystal X-ray diffraction.The crystal is of orthorhombic,space group Pccn with a = 16.7246(10),b = 19.6626(12),c = 9.3013(6) ,V = 3058.7(3) 3,Z = 8,Dc = 1.402 g/cm3,μ = 0.269 mm-1,F(000) = 1344,the final R = 0.0506 and wR = 0.1464 for 2568 reflections with I 2σ(I).In addition,disordered C(14) and C(15) atoms exist in the crystal structure.     

Synthesis and Characterization of （4R,5R）-1,3-dioxolance-4,5-bis（2-pyridineacrboxylic acid）

The title compound, (4R,5R)-1,3-dioxolance-4,5-bis(2-pyridineacrboxylic acid), has been synthesized and characterized by single-crystal X-ray diffraction, IR, NMR, and MS analyses. Crystal structure of the title compound was grown from ETOH by slow diffusion at room temperature. The title compound crystallizes in monoclinic, space group C2 with a = 17.805(3), b = 11.459(3), c = 11.1656(17) , β = 113.066(4)°, V = 2095.9(6) 3, Z = 4, F(000) = 880, Dc = 1.332 Mg/m-3, C23H20N2O6, Mr = 420.41 and μ = 0.10 mm-1     

Synthesis and Crystal Structure of 4-[（1E）-（4-Hydroxy-3,5-dimethoxybenzylidene）-amino]-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazol-3-one

The title compound (C20H21N3O4, Mr = 367.40) has been synthesized and its crystal structure was determined by single-crystal X-ray diffraction. The crystal is of orthorhombic, space group P212121 with a = 7.5143(15), b = 13.901(3), c = 18.545(4) , V = 1937.1(7) 3, Z = 4, Dc = 1.260 g/cm3, μ = 0.089 mm-1, F(000) = 776, the final R = 0.0616 and wR = 0.0912. X-ray diffraction reveals that the molecule adopts an E configuration about the central C=N double bond. The intermolecular O–H…O hydrogen bond stabilizes the crystal structure by causing the formation of a supramolecular architecture.     

Synthesis, Crystal Structure and Antidepressant Activity of 5-[4-(Benzyloxy)phenyl]-9-(n-propyl)-4,6-dioxa-1-azabicyclo[3.3.1]nonane Hydrochloride 0.5Hydrate

The title compound 2(C22H28N+O3)·H2O·2Cl-was synthesized by the reaction of 2-bromo-1-[4-(benzyloxy)phenyl]-1-pentone with 2,2'-azanediyldiethanol. The crystal determined by X-ray diffraction analysis belongs to the monoclinic system, space group Pc with a = 18.312(3), b = 14.838(3), c = 7.6227(14) , β = 97.981(4)°, Z = 2, Mr = 797.82, V = 2051.1(6) 3, Dc = 1.292 g/cm3, S = 0.956, μ = 0.21 mm-1, F(000) = 852, the final R = 0.0625 and wR = 0.1428 for 5683 observed reflections (Ⅰ > 2σ(Ⅰ)). Flack parameter is 0.10(9). The title compound is composed by four non-coplanar ring systems, two benzenes and two morpholines. One morpholine ring (C(3)-C(4)-N(1)-C(1)-C(2)-O(1)) forms a chair conformation, while the other (C(4)-C(3)-O(2)-C(6)-C(5)-N(1)) assumes a boat conformation. X-ray crystal structure displays extensive N-H…Cl and O-H…Cl intermolecular hydrogen bonds. The preliminary antidepressant activity test indicates that the inhibition ratio of SERT (5-HT Transporter) was 35.9% at the dosage of 10.0 mg/L.     

Synthesis and Crystal Structure of (Z)-Ethyl-4-(4-methoxy)benzylidene-2-(3,5-dimethoxypheny-tetrahydrofuran-3,3-dicarboxylate

The title compound (Z)-ethyl-4-(4-methoxy)benzylidene-2-(3,5-dimethoxyphenyl)- tetrahydrofuran-3,3-dicarboxylate has been synthesized, and its crystal structure was characterized by X-ray single-crystal diffraction. The crystal belongs to triclinic, space group P1-, with a = 8.140(3), b = 11.966(4), c = 13.771(5) α = 67.366(4), β = 85.165(5), γ = 75.806(4)°, V = 1200.1(7) 3, Z = 2, C26H30O8, Mr = 470.50, Dc = 1.302 g/cm3, F(000) = 500, λ(MoKα) = 0.71073 , μ = 0.096 mm–1, R = 0.0659 and wR = 0.1841 for 3080 observed reflections (I > 2σ(I)). As a key intermediate of HIV-1 integrase inhibitor, the synthesis and structure confirmation of the title compound are important for further studies.     

Synthesis, Crystal Structure and Inhibition of N-2-Thiophenesulfonyl-α-L-phenylalanine Ethyl Ester on K562 Cell Proliferation

The title compound N-2-thiophenesulfonyl-α-L-phenylalanine ethyl ester has been synthesized. Complete assignments were achieved by IR, MS, 1H NMR and single-crystal X-ray diffraction analyses. Using MTT assay, the inhibitory rate of the title compound on K562 cells (chronic myeloid 1eukemic cells) was measured and the result of preliminary bioassay showed that the title compound possesses antiproliferation effects on K562 cells. In order to investigate the relationship between structure and activity of the target compound, we report its crystal structure and biological behavior in the present paper. Crystallographic data: C15H17NO4S2, Mr = 339.42, monoclinic, space group P21, flack = –0.15(12), a = 5.7916(10), b = 11.5078(19), c = 12.924(2) , β = 97.781(3)o, Z = 2, V = 853.4(2) 3, Dc = 1.321 g/cm3, F(000) = 356, –7≤h≤7, –10≤k≤14, –15≤l≤15, R = 0.0628, wR = 0.1540 and μ(MoKα) = 0.327 mm-1. The molecule comprises a benzene and a thiofuran rings, and the intramolecular N(1)–H(1A)…O(1) makes a five-membered ring of O(1)–C(6)–C(5)–N(1)–H(1A).     

Synthesis,Crystal Structure and Antifungal Activities of 3-Methyl-1-(4-methylphenyl)-4-(N-4-trifluoromethylphenyl)-aminomethyl-5-(4-methoxyphenylthio)-1H-pyrazole

The title compound 3-methyl-1-(4-methylphenyl)-4-(N-4-trifluoromethylphenyl) aminomethyl-5-(4-methoxyphenylthio)-1H-pyrazole has been synthesized via a four-step reaction and characterized by IR,1H NMR,elemental analysis and X-ray crystallography.The compound crystallizes in monoclinic,space group P21/c with a = 8.7170(15),b = 18.355(3),c = 15.292(3) ,β = 103.445(3)°,V = 2379.7(7) 3,Dc = 1.350 g/cm3,Z = 4,μ = 0.184,F(000) = 1008,and the final R = 0.0491 and wR = 0.1339 for 4160 observed reflections(I 2σ(I)).The results demonstrate that there is a face-to-face π-π stacking interaction between one benzene ring(C(19)~C(24)) and another(C(13)~C(18)) at a plane-plane distance of 3.3539 .The ring normal and vector between the ring centroids form an angle of 18.2o up to the centroid-to-centroid distance of 3.5273 .The crystal structure is stabilized by the intermolecular hydrogen bond of N(3)-H(3A)···N(2)(symmetry code:A –x+1,–y+1,–z).The preliminary biological test shows that the title compound has a moderate antifungal activity.