Neue β-Lactam-Antibiotika. Zur Funktionalisierung von 3-Hydroxy-3-cephem-4-carbonsäureestern durch die Wittig-Reaktion. Modifikationen von Antibiotika. 16. Mitteilung [1]

New β-lactam antibiotics. Functionalisation of 3-hydroxy-3-cephem-4-carboxylic esters through the Wittig reaction The 3-hydroxy-ceph-3-em-esters 1a, b reacted smoothly with stabilized phosphor-ylids to give a series of derivatives which were converted into the microbiologically active acids 14a, c, 15c and 20 by known procedures. The synthesis of the amides 23, 24, 26 and of the ester 28 from the 3-carboxymethyl-derivative 19 is also reported.     

Quantum chemical and master equation simulations of the oxidation and isomerization of vinoxy radicals

The vinoxy radical, a common intermediate in gas-phase alkene ozonolysis, reacts with O2 to form a chemically activated alpha-oxoperoxy species. We report CBS-QB3 energetics for O2 addition to the parent (*CH2CHO, 1a), 1-methylvinoxy (*CH2COCH3, 1b), and 2-methylvinoxy (CH3*CHCHO, 1c) radicals. CBS-QB3 predictions for peroxy radical formation agree with experimental data, while the G2 method systematically overestimates peroxy radical stability. RRKM/master equation simulations based on CBS-QB3 data are used to estimate the competition between prompt isomerization and thermalization for the peroxy radicals derived from 1a, 1b, and 1c. The lowest energy isomerization pathway for radicals 4a and 4c (derived from 1a and 1c, respectively) is a 1,4-shift of the acyl hydrogen requiring 19-20 kcal/mol. The resulting hydroperoxyacyl radical decomposes quantitatively to form *OH. The lowest energy isomerization pathway for radical 4b (derived from 1b) is a 1,5-shift of a methyl hydrogen requiring 26 kcal/mol. About 25% of 4a, but only approximately 5% of 4c, isomerizes promptly at 1 atm pressure. Isomerization of 4b is negligible at all pressures studied.     

Synthesis and Antioxidant Evaluation of Some New Pyridopyrazolotriazine Derivatives

Diazodization of pyrazolo[3,4‐b]pyridine 1 afforded diazonium salt 2 that coupled with active methylene compounds such as 3a , 3b , 6 , 7 , 8 , 15a , 15b , 16a , 16b , 17 , and 24 in pyridine to give aryl hydrazone derivatives 4a , 4b , 9 , 10 , 11 , 18a , 18b , 19a , 19b , 20 , and 25 , respectively. The previous synthesized compounds underwent cyclization in acetic acid to give the corresponding pyridopyrazolotriazines 5a , 5b , 12 , 13 , 14 , 21a , 21b , 22a , 22b , 22c , 23 , and 26 , respectively. The newly synthesized compounds were characterized by elemental analysis and spectral data and screened for their antioxidant activities. The results of ABTS method showed clearly that compounds 1 , 4b , 5b , 11 , 20 , 25 , and 26 displayed promising in vitro antioxidant activities. Compounds 1 and 4a exhibited high protection against DNA damage induced by the bleomycine iron complex.     

Synthetic study for two 2H‐chromenic acids, 8‐chlorocannabiorcichromenic acid and mycochromenic acid

Two 2H‐chromenes having a fully substituted benzene ring, 8‐chlorocannabiorcichromene ( 1 ) and mycochromenic acid ( 2 ), were synthesized by a condensation of salicylaldehydes with isopropylidenemalonate or the thermal cyclization of corresponding propargyl ethers.     

Lewis acid-promoted hetero Diels-Alder cycloaddition of alpha-acetoxynitroso dienophiles

[reaction: see text] alpha-Acetoxynitroso compound 3 has been prepared as a new stable, isolable, and reactive dienophile in nitroso Diels-Alder reactions. The yield of the [4 + 2] cycloaddition of alpha-acetoxynitroso dienophile with 1,3-dienes could be enhanced in the presence of 20 mol % Lewis acid. An unexpected retro hetero-Michael reaction from 26 was observed, leading to the cleavage of the N-O bond of the cycloadduct. This tandem nitroso Diels-Alder/retro hetero-Michael sequence has been used with cyclic and acyclic 1,3-dienes.     

Synthesis and Crystal Structure of 1＇-Methyl-4＇-（4-chlorophenyl）-1H-indole-3-spiro-2＇-pyrrolidine-3＇-spiro-4＂-（2＂-phenyloxazole）-2,5＂（3H,4＂H）-dione

The title compound （C26H20ClN3O3） has been synthesized by 1,3-dipolar cycloaddition reaction from isatin, sarcosine and （Z）-4-（4-chlorobenzylidene）-2-phenyloxazol-5（4H）-one through a one-pot procedure, and its structure was confirmed by IR, IH NMR, elemental analysis and single-crystal X-ray diffraction analysis. The crystal belongs to the triclinic system, space group PI, with a = 9.3903（19）, b = 11.398（2）, c = 12.603（3） A, α = 83.495（3）, β = 68.988（3）, γ = 67.178（3）^o, V= 1160.1（4）A^3 Z = 2, Mr= 457.90, Dc= 1.311 g/cm^3, p = 0.198 mm ^-1, F（000） = 476, the final R = 0.0489 and wR = 0.1144 for 3109 observed reflections with I 〉 2σ（I）.     

Synthesis of Thiadiazolinylpyrazolopyridine and Pyridopyrazolotriazine Derivatives

3‐Diazotized aminopyrazolo[3,4‐b]pyridines 2a,b used as good synthons for the synthesis of 3‐thiadiazolinylpyrazolo[3,4‐b]pyridines 8a,b through their reactions with thiocyanatoacetophenone ( 6 ) and pyrido[2,3:3′,4′]pyrazolo[5,1‐c][1,2,4]triazines 5a‐d via their reactions with several active methylene containing reagents: 3a,b, 12, 16, 20, 23a‐d and 26a‐c . All the structures of the newly synthesized heterocyclic compounds were established by considering the data of IR,¹H NMR and mass spectra in addition to the synthesis of most newly synthesized heterocyclic compounds via other routes.     

Über die Decamethylferroceniumpolyiodide [(Me5C5)2Fe]Ix mit x = 3, 5 und 6,5. Darstellung und strukturelle Charakterisierung eines Triiodids (DMFc)I3, eines Pentaiodids (DMFc)I5 und eines Hexacosaiodids (DMFc)4I26

Studies on Polyhalides. 30 On Decamethylferriciniumpolyiodides [(Me₅C₅)₂Fe]I_x with x = 3, 5, 6.5: Preparation and Crystal Structures of a Triiodide (DMFc)I₃, a Pentaiodide (DMFc)I₅ and a Hexacosaiodide (DMFc)₄I₂₆ Decamethylferrocene (DMFc) may be oxidized by iodine analogous to ferrocene (Fc) to the decamethylferrocenium ion (DMFc)⁺ and precipitated as the crystalline solids decamethylferrocenium triiodide (DMFc)I₃, decamethylferrocenium pentaiodide (DMFc)I₅ and tetracisdecamethylferrocenium hexacosaiodide (DMFc)₄I₂₆. The two compounds with higher iodine content are new. These are characterized by X-ray diffraction methods on single crystals. The structures are built up from complex cations of expected geometry and isolated or remarkably connected polyiodide ions. Decamethylferrocenium triiodide C₂₀H₃₀FeI₃ crystallizes monoclinically in C2/m with a = 1489.9(4) pm, b = 1133.0(2) pm, c = 765.9(3) pm, β = 111.76(3)° and Z = 2. The crystal structure follows the CsCl-type and contains isolated triiodide ions of the linear symmetric form. Decamethylferrocenium pentaiodide C₂₀H₃₀FeI₅ crystallizes monoclinically in P2₁/c with a = 1130.0(2) pm, b = 1442.6(1) pm, c = 1716.6(2) pm, β = 96.62(1)° and Z = 4. The crystal structure may be deduced from the primitiv quadratic bundle of alternating cationic and anionic rods. It contains exceptionally isolated somewhat opened out pentaiodide ions. Tetrakisdecamethylferrocenium hexacosaiodide (C₂₀H₃₀Fe)₄I₂₆ crystallises monoclinically in P2₁/n with a = 1331.3(8) pm, b = 1319.4(4) pm, c = 3564(2) pm, β = 90.84(5)° and Z = 2. The crystal structure of this compound with unusual composition may be described as an inclusion compound with channels for the cations. The outstanding anionic grating may be derived from the primitive cubic lattice of iodide ions with iodine bridges on all edges by removing systematically 1/12 of the iodine molecules.     

新型3-五元碳环螺环氧化吲哚类化合物的合成及其抗人白血病细胞活性

以氧化吲哚与邻芳基二甲醛为原料,经Knoevenagel缩合(或Michael,环化反应),制得7个3-五元碳环螺环氧化吲哚(4a~4c,产率67%~86%,d/r值4∶1~10∶1)和4d~4g;4d~4g与哌啶(或四氢吡咯)和多聚甲醛经胺甲基化反应,合成了4个3-五元碳环螺环氧化吲哚(5d~5g),产率55%~67%,d/r值10∶1~20∶1,其结构经~1H NMR,~(13)C NMR和HR-MS(ESI-TOF)表征。采用MTT法研究了4a~4c和5d~5g对人白血病细胞(K562)的体外抗肿瘤活性。结果表明:4b,5d和5f对K562抑制活性较好,IC50分别为29.3μmol·L~(-1),27.4μmol·L~(-1)和34.2μmol·L~(-1),与阳性对照药顺铂(26.8μmol·L~(-1))相当。     

Syntheses and Structures of Two Copper Compounds Supported by Octamolybdate

1INTRODUCTION More and more chemists have currently been inte-rested in the transition metal oxides(so-called polyoxometalates)mainly owing to their structural varieties and promising potential applications in catalysis,biology,medicine and materials science[1].Of the various polyoxometalate structures,the most interesting one is the molybdate family with a va-riety of structural polymers including{Mo2},{Mo4},{Mo6},{Mo8}.etc.These molybdate polymersmight act as versatile building blocks …     

3,3-二甲基-9-(5,5-二甲基-3-羟基-2-环己烯-1-酮-2-基)-1-氧代-2,3,4,9-四氢化氧杂蒽的合成和晶体结构

标题化合物C23H26O4是由水杨醛与5，5-二甲基-1，3-环己二酮在N，N-二甲基甲酰胺中反应而得．结构通过单晶X-射线行射法确定，其晶体属于单料晶系，空间群P21/c，a=7．056（7），b=20.263（3），c=13．665（2）A，β＝93．32（1）°，V=1950．7（4）A3，Mr=366．46，Dc=1.248g／cm3，Z=4，μ（MoKa）=0．84cm－1，F（000）=784。晶体结构用直接法解出，经全矩阵最小二乘法对原子参数进行修正，最后的偏离因子R=0．068，Rw=0．075。晶体结构分析结果表明，分子中存在一个共轭的烯醇式结构。     

Crystal Structure of O,O'-Diphenyl N-(o-methylphenyl)-P-toluenesulfonamidomethylphosphonate

1INTR0DUCT10NThederivativesofaaminoph0sphonicacidhaveversatilebiologicalactivities-`13Inordertolookforhighlyeffectiveandselectivenewpesticides,aseriesofdiethyl1-(P-tohienesulfonamido)methylphosphonates1havebeensynthesizedbyathree-com-P0nentreacti0nofp-t0luenesulfonamide,formaldehydeandtriphenylphosphite.t2j'The1HNMRspectraoftheprbductsin-dicatethatthetwohydrogenatoms0ntheaCatomaremagneticallyequivalentwhenthesubstitutedgroupsonNatomareH,CH3andEt02CCHz'However,(R=H.Me,EtO,CCH,,o-me…     

Further studies on synthesis of the 12,13-seco norditerpenoid alkaloids

After a series of optimization for the reaction conditions (reagents, reaction temperature, etc.), treatment of the sulfonates 4, 8, 13 and 15 with 8% NaOH (room temperature, 24 h) via a semipinacol rearrangement afforded the corresponding C-nor compounds 5, 9, 12 and 16, as the major of a pair of epimer at C-16, to an excellent extent, in 95%, 92%, 100% and 90% yield, respectively. The 12,13-seco compounds 21 and 22 (23) were obtained in 20% and 60% yield, respectively, by treating 5 with Br(2)-glacial HOAc (room temperature, 24 h). Treatment of the C-nor compounds 5 or 6, 16 or 17, and 28 from 10 with SOCl(2)-anhydrous benzene (room temperature, overnight) afforded the 12,13-seco compounds 24, 26 and 30 in 70% or 100%, 40% and 66% yield, respectively. When treatment of the C-nor compound 29 from 9 under same conditions gave the 12,13-seco products 30, 31 and 32 in 33%, 26% and 20% yield. When treating 21 or 24, and 26 with 5% KOH in EtOH afforded the 12,13-seco compounds 25 and 27 quantitatively, respectively. The compound 31 converted to 30 quantitatively by treatment with Na(2)CO(3) in MeOH. All of the new compounds were isolated and fully characterized.     

Spiropentane mimics of nucleosides: analogues of 2'-deoxyadenosine and 2'-deoxyguanosine. Synthesis of all stereoisomers, isomeric assignment, and biological activity

Synthesis of spirocyclic analogues of 2'-deoxyadenosine and 2'-deoxyguanosine (12a-15a and 12b-15b) is described. Rhodium-catalyzed reaction of ethyl diazoacetate with methylenecyclopropane 19, obtained from 2-bromo-2-bromomethylcyclopropane 17 via debromination (16), reduction (18), and acetylation (19), gave a mixture of all four isomeric spiropentanes 20a-20d. Hydrolysis afforded hydroxy carboxylic acids 21a-21d. Acetylation of separated proximal + medial-syn isomers 21a + 21b and medial anti + distal isomers 21c + 21d furnished acetates 22a + 22b and 22c + 22d. Curtius rearrangement effected by diphenylphosphoryl azide in tert-butyl alcohol performed separately with mixtures 22a + 22b and 22c + 22d led to BOC-amino spiropentanes 23a + 23b and 23c + 23d. After deacetylation all isomers 24a-24d were separated and deprotected to give aminospiropentane hydrochlorides 25a-25d. Free bases were of limited stability. The heterocyclic moieties were introduced into individual isomers 25a-25d via 6-chloropurine derivatives 26a-26d or 30a-30d. Ammonolysis of 26a-26d furnished the adenine isomeric series 12a-15a, whereas guanine derivatives 12b-15b were obtained by hydrolysis of 30a-30d with formic acid. The isomeric assignments followed from IR spectra of BOC-aminospiropentanes 24a-24d and NMR spectra of 12a-15a including NOE and (H,H) COSY. The proximal and medial-syn isomers 12a and 12b were modest inhibitors of human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in culture, whereas the medial-anti isomer 12c was a substrate for adenosine deaminase. The distal isomer 15b was an anti-EBV agent. The medial-syn phosphoralaninate 34 was an effective inhibitor of HCMV replication in vitro. It was also active against herpes simplex virus type 1 (HSV-1), varicella zoster virus (VZV), human immunodeficiency virus (HIV-1), hepatitis B virus (HBV), and EBV with a varying degree of cytotoxicity.     

Substrate specificity of Rv3378c, an enzyme from Mycobacterium tuberculosis, and the inhibitory activity of the bicyclic diterpenoids against macrophage phagocytosis

The Rv3378c gene product from Mycobacterium tuberculosis encodes a diterpene synthase to produce tuberculosinol (3), 13R-isotuberculosinol (4a), and 13S-isotuberculosinol (4b) from tuberculosinyl diphosphate (2). The product distribution ratios are 1 : 1 for 3 to 4 and 1 : 3 for 4a to 4b. The substrate specificity of the Rv3378c-encoded enzyme was examined. The 3 labdadienyl diphosphates, copalyl diphosphate (CDP) (7), ent-CDP (8), and syn-CDP (9), underwent the conversion reaction, with good yields (67-78%). Copalol (23) and manool (24) were produced from 7, ent-copalol (25) and ent-manool (26) from 8, and syn-copalol (27) and vitexifolin A (28) from 9. The ratio of 23 to 24 was 40 : 27, that of 25:26 was 22 : 50, and that of 27:28 was 16 : 62. Analysis on a GC-MS chromatograph equipped with a chiral column revealed that 24, 26, and 28 consisted of a mixture of 13R- (a) and 13S-stereoisomers (b) in the following ratio: ca. 1 : 1 for 24a to 24b, ca. 1 : 5 for 26a to 26b, and ca. 1 : 19 for 28a to 28b. The structures of these products indicate that the reactions of the 3 CDPs proceeded in the same fashion as that of 2. This is the first report on the enzymatic synthesis of natural diterpenes manool, ent-manool, and vitexifolin A. Both Rv3377c and Rv3378c genes are found in virulent Mycobacterium species, but not in avirulent species. We found that 3 and 4 inhibited the phagocytosis of opsonized zymosan particles by human macrophage-like cells. Interestingly, the inhibitory activity was synergistically increased by the coexistence of 3 and 4b. Other labdane-related diterpenes, 13-16 and 23-28, had little or no inhibitory activity. This synergistic inhibition by 3 and 4 may provide further advantage to the impairment of phagocyte function, which might contribute to pathogenicity of M. tuberculosis.     

Regioselective cyclodehydration of ortho‐hydroxy acetyl aryloxyketones to benzofuran

ortho‐Hydroxy acetyl benzofuran derivatives have been synthesized in a regioselective cyclodehydration of aryloxyketones obtained from β‐resacetophenone and α‐halo ketones.     

Effects of water uptake on the inherently oxygen-deficient compounds Ln26O27 square(BO3)8 (Ln=La, Nd)

The inherently oxygen-deficient compounds Ln26O27 square(BO3)8 (Ln=La, Nd) react with water vapor leading to Ln26O26(OH)2(BO3)8 phases, and this reaction is reversible. The crystal structure of Nd26O27 square(BO3)8 has been determined from single-crystal data (space group P with a=6.7643(10) A, b=12.663(2) A, c=14.271(2) A, alpha=90.553(8) degrees, beta=99.778(10) degrees, and gamma=90.511(9) degrees). It is a triclinic distorted version of the monoclinic structure of La26O27 square(BO3)8. The Ln26O26(OH)2(BO3)8 phases both crystallize in the monoclinic system (space group P21/c with a=6.7445(4) A, b=12.6177(9) A, c=14.4947(10) A, and beta=100.168(7) degrees for Nd26O26(OH)2(BO3)8 and a=6.9130(15) A, b=12.896(3) A, c=14.792(4) A, beta=99.698(16) degrees for La26O26(OH)2(BO3)8), and their crystal structure has been determined from single-crystal data, showing that the hydroxyl groups are localized mainly on one of the oxygen sites at room temperature (RT). For the Nd phases, the change in crystal system can result from two different phenomena depending on the atmosphere, either a phase transformation corresponding to a water uptake under wet conditions (triclinic Nd26O27 square(BO3)8 at RT-->monoclinic Nd26O26(OH)2(BO3)8) or a phase transition at approximately 300 degrees C for the anhydrous phase under dry conditions (triclinic Nd26O27 square(BO3)8 at RT-->monoclinic Nd26O27 square(BO3)8 at T>300 degrees C). For Nd26O26(OH)2(BO3)8, the conductivity measured under wet conditions at 300 degrees C is sigma300 degrees C approximately 0.5x10(-5) S cm(-1). Due to the dehydration process, the proton contribution to the total conductivity of the Nd phase is no longer observed above 500 degrees C whereas it was still clearly visible at 600 degrees C for the La phase.     

Structure of 7, 8, 17, 18-Tetrabromo-5,10,15, 20-Tetraphenylporphinatozinc(Ⅱ)

1mrnODUCTIONRecentlywereportedthestructureof7,8,17,18--tetrabromo--5,10,15,20--tetraphenylporphinatozinc(H,TPPBr.)ill.Inordertoobservetheeffectofthefoulelectron--withdrawingbromogroupsonthestructureofametalcomplexofthisPOrphyrin,thetitlecompoundwaspreparedbyanestablishedmethod[Ziandthecrysta:wasobtained,whichissuitableforstructureanalysisbylayeringasolutioninCHCI,withpetroleum(60--90C)--piperidine.2EXPERIMENTALThetitlecomplexwassynthesizedbyreactionofH,TPPBr.andZn(CH,COO):.ZH…