The Effective Catalyst (Cobalt Salt/Lewis Acid) for Beckmann Rearrangement of Cycloalkanone Oximes to Lactams under Mild Conditions

The Beckmann rearrangement of cyclohexanone oxime was achieved by the combined use of cobalt salt and Lewis acids co-catalysts (each 10 mol%). Various combinations of cobalt salts and Lewis acids gave lactams in a satisfactory yield under mild conditions. This method makes it possible to reduce undesirable byproducts.

Anion cascade reactions Ⅲ:Synthesis of 3-isoquinuclidone bridged polycyclic lactams

Bridged polycyclic lactams are important structural units in organic functional materials,natural products,and pharmaceuticals.A flexible and efficient anion cascade reaction was developed for the preparation of bridged polycyclic lactams from readily available malonamides and 1,4‑dien-3-ones.Various highly substituted bridged polycyclic lactams were synthesized in good to excellent yields by tandem nucleophilic sequences in the presence of t BuOK in commercially available EtOH solvent at 60℃.Notably,the simple reactions can be run on a gram scale.Mechanistically,bis-Michael addition reaction and hemiaminalization reactions are involved in the tandem transformation.

Structural diversification of phenylspirodrimane lactams by employing a biosynthetic intermediate

Phenylspirodrimanes are a kind of meroterpenoids with structural diversity and complexity,exhibiting a wide of biological properties,especially for the lactam derivatives consisting a y-lactam moiety and N-linked side chains.These compounds were derived from multi-step combination of enzymatic and non-enzymatic conversions of intermediates in their biosynthetic pathways.Stachbotrydial(2)with an o-phthalaldehyde unit was supposed as the high-reactivity intermediate of phenylspirodrimane lactams via nonenzymatic reaction with amines.In the present work,an effective and non-enzymatic diversification strategy was developed for the structural diversification of phenylspirodrimane lactams including monomers and dimers from 2 by feeding structurally various mono-and diamines in the fungus Stachybotrys chartarum cultures.In total,24 phenylspirodrimane lactams(1,3-25)including 18 new compounds were synthesized.Among them,stachybocin A(1),a bioactive phenylspirodrimane lactam dimer,was produced with the yield of 18.7 mg/g of cell dry weight.The structures of these compounds were elucidated by extensive spectroscopic data,single-crystal X-ray diffraction(Cu Kα),and calculated electronic circular dichroism(ECD)analyses.Bioassay revealed that compounds 1,17,and 24 displayed significant inhibitory effect on the inactivated state of hNav 1.2 channels with IC_(50) values of 0.22,2.08,and 0.53μmol/L,respectively.In addition,1 showed potent protein tyrosine phosphatase 1B(PTP1B)inhibitory N-methyl-b-aspartate(NMDA)receptor antagonistic,and anti-inflammatory activities.

Catalytic hydrative cyclization of aldehyde-ynamides with water for synthesis of medium-sized lactams

A non-noble metal catalyzed hydrative cyclization of aldehyde-ynamides for efficient and practical synthesis of medium-sized lactams(7-to 9-membered rings)is disclosed.Compared with previous hydrative cyclization for the formation of six-membered lactams(cis-form),a totally inverse diastereoselectivity(trans-form)of medium-sized lactams is observed.In addition,this protocol delivers valuable medium-sized lactams in moderate to good yields with high diastereoselectivities.Moreover,a rational mechanism to understand this inversion of diastereoselectivity is proposed based on theoretical calculations.

Organocatalytic dynamic kinetic resolution of N-arylindole lactams:atroposelective construction of axially chiral amino acids bearing a C–N chiral axis

Organocatalytic dynamic kinetic resolution of configurationally labile cyclic molecules represents one of the most efficient methods for the atroposelective construction of axially chiral molecules bearing a tetra-ortho-substituted chiral axis.Notably,this privileged strategy is limited to constructing a C–C chiral axis.Herein,organocatalytic dynamic kinetic resolution of configurationally labile N-arylindole lactams has been successfully achieved at the first time,allowing for access to a structurally diverse set of axially chiral N-arylindole amino esters with a tetra-ortho-substituted C–N chiral axis in excellent yields and atroposelectivities.In addition to the N-arylindole skeleton,N-aryl thieno[3,2-b]pyrrole,furo[3,2-b]pyrrole,and pyrrolo[2,3-b]pyridine skeletons are also compatible with this transformation.This transition-metal-free facile strategy features a broad substrate scope,mild reaction conditions,easy scale-up and excellent atom economy.Several potentially valuable molecules,such as axially chiral peptides,were efficiently generated from the resulting configurationally stable axially-chiral N-arylindole amino esters,demonstrating the power of this strategy.

A Dipolar Cyclization/Fragmentation Strategy for the Catalytic Asymmetric Synthesis of Chiral Eight-Membered Lactams

Medium-sized nitrogen heterocycles,including eightmembered lactams,are important in synthetic and pharmaceutical chemistry because of their presence in a variety of natural products and drug molecules.Previous attempts at synthesis using a direct headto-tail cyclization strategy suffered from competitive self-cyclization and oligomerization of dipolar species.Herein,we propose an alternative strategy.

Ruthenium(Ⅱ)-cored supramolecular organic framework-mediated recyclable visible light photoreduction of azides to amines and cascade formation of lactams

Ru(bpy)3]2+-cored supramolecular organic framework SMOF-1, assembled from a [Ru(bpy)3]2+-derived hexaarmed molecule and cucurbit[8]uril, has been demonstrated to heterogeneously catalyze visible light-induced reduction of phenyl, benzyl, 2-phenylethyl and 3-phenylpropyl azides in acetonitrile to produce the corresponding amines in good to high yields. For the last two kinds of azides that bear a CO2Me group at the para-position of the benzene ring, cascade reactions take place to generate the corresponding lactams in high yields. Compared with homogeneous control [Ru(bpy)3]Cl2, SMOF-1 exhibits remarkably increased photocatalysis activity as a result of synergistic effect of the [Ru(bpy)3]2+ units that form cubic cages to host the azide molecules and related intermediates. Moreover, SMOF-1 displays high recyclability and considerable photocatalysis activity after 3 to 12 runs.

Steric-switched defluorofunctionalization selectivity: controlled synthesis of monofluoroalkene-masked medium-sized heterocyclic lactams and lactones

The steric-switched ipso-defluoroamination-triggered and ipso-defluorooxylation-triggered cyclization of(trifluoromethyl)alkenes with amino alcohols and diamines are achieved under mild conditions. This regioselective strategy distinguishes the different nucleophilic heteroatom sites in amino alcohols and unsymmetric diamines by the sequential defluorinative functionalization of two C(sp^(3))–F bonds in a CF_(3) group. Various attractive monofluoroalkene-masked medium-sized heterocyclic lactams and lactones are obtained in moderate to excellent yields. Simple derivation of these masked-heterocycles efficiently affords useful skeletons of lactams, lactones, and 1,4-oxazepanes in a single diastereoisomer. Mechanism studies indicate that a unique sequential ipso-/γ-selective defluorinative functionalization pathway is involved in these transformations.

Electrochemical Ring Expansion to Synthesize Medium-Sized Lactams Through C–C Bond Cleavage

Medium-sized nitrogen heterocycles are prevalent motifs in many kinds of bioactive molecules and natural products.Owing to the unfavorable enthalpic and entropic barriers during the transition states,access to medium-sized rings is challenging.Herein,a general and practical electrochemical ringexpansion protocol has been developed from commercially available benzocyclic ketones and amides.In this regard,a series of highly functionalized eightto eleven-membered lactams could be successfully accessed in high yields and efficiencies.

苏州地区儿童感染流感嗜血杆菌β内酰胺酶基因检测

目的 了解苏州地区儿童感染流感嗜血杆菌(Hi)对氨苄西林的耐药情况,并从分子生物学的角度研究其耐药机制。方法 对135株Hi临床分离株用K B法作药敏试验,头孢硝噻吩显色法进行β内酰胺酶测定,PCR法进行β内酰胺酶基因TEM、ROB测定。结果 本地区儿童感染Hi对氨苄西林的耐药率为17.8%,所有耐药株均产β内酰胺酶,未发现β内酰胺酶阴性耐氨苄西林Hi (BLNAR)菌株。β内酰胺酶基因TEM的检出率为27.4%(10.4%氨苄西林敏感株也检出TEM基因),ROB为0.7%(该ROB型株同时携带TEM 基因),发现1株非TEM非ROB 型产β内酰胺酶Hi。结论 本地区儿童感染Hi对氨苄西林的耐药情况不容乐观,其耐药机制主要是产生β内酰胺酶,且以TEM型为主,携带TEM基因的氨苄西林敏感株的出现,是否预示新一轮氨苄西林耐药株的产生,值得关注。

哌拉西林/舒巴坦对β-内酰胺酶稳定性及抑酶增效作用研究

目的:比较哌拉西林、哌拉西林/舒巴坦、氨苄西林/舒巴坦、头孢哌酮/舒巴坦和哌拉西林/他唑巴坦对23株临床分离革兰阴性杆菌和7株标准菌所产生β-内酰胺酶的稳定性。方法:对23株临床分离革兰阴性杆菌用Etest法检测ES-BL,用三维法检测Amp C酶。以生物法测定酶对抗生素的相对水解率,抑酶保护率。结果:临床分离致病菌23株中18株产ESBLs,Amp C酶全部为阴性。结果表明哌拉西林/舒巴坦(4∶1)与氨苄西林/舒巴坦(2∶1)和头孢哌酮/舒巴坦(1∶1)的相对水解率和抑酶保护率相同(P>0.05)。哌拉西林/舒巴坦(4∶1)的相对水解率高于哌拉西林/他唑巴坦(P<0.05)。结论:舒巴坦与哌拉西林复方提高了哌拉西林对革兰阴性杆菌所产β-内酰胺酶(包括ESBLs)的稳定性,增强了抗菌作用。

常见革兰阴性杆菌高活性β-内酰胺酶的检测

目的 通过对常见革兰阴性杆菌进行ESBLs和高产AmpC酶的检测 ,了解其在临床的检出率 ,以指导临床用药。方法 用改良的酶提取物三维试验方法进行持续高产AmpC酶和ESBLs的检测 ,并用此法与双纸片扩散法进行比较。 结果 在常见革兰阴性杆菌中高产AmpC酶分别为阴沟肠杆菌 2 0 4%,鲍曼不动杆菌 16.7%,弗劳地枸橼酸杆菌 10 0 %,铜绿假单胞菌 8.6%,肺炎克雷伯菌 7 1%,大肠埃希菌4 4%;ESBLs的检出率分别为肺炎克雷伯菌 2 8 6%,大肠埃希菌 2 7 9%,阴沟肠杆菌 18 4%,鲍曼不动杆菌 13 3 %,铜绿假单胞菌 8 6%。对同时产两类酶的菌株双纸片扩散法检测ESBLs可出现假阴性。结论 对革兰阴性杆菌可使用改良的三维法同时进行ESBLs和高产Am pC酶的检测 ,双纸片扩散法检测ESBLs可应用于所有革兰阴性杆菌的检测 ,但应注意有假阴性 。

肺炎链球菌耐药基因及其分子生物学检测

肺炎链球菌(Streptococcus pneumoniae,SPN)是引起儿童呼吸道感染的常见病原菌。自1990年来,SPN菌在耐药性方面的流行性逐渐增加,引起国内外学者的广泛关注。而今年来,国内外均报道临床分离得到的SPN菌株对青霉素,红霉素,四环素和喹诺酮类药物耐药性呈上升趋势。

某院儿科2016-2017年流感嗜血杆菌的分布特征及耐药性分析

目的回顾性分析2016年1月至2017年12月本院儿科住院患者流感嗜血杆菌分布特征,并对常用抗菌药物药敏结果进行分析,为临床合理使用抗生素提供选择依据.方法用含有Ⅴ因子、Ⅹ因子的巧克力培养基分离培养流感嗜血杆菌,通过VITEK-2全自动微生物鉴定分析仪进行菌种鉴定.用琼脂扩散（K-B）法进行药敏试验.同时用头孢硝噻吩纸片检测β-内酰胺酶.结果2年共分离到流感嗜血杆菌156株.其中以1岁以下婴幼儿及每年第2季度检出率最高.同时可见合并有肺炎链球菌等其他病原菌感染.药敏结果显示,复方磺胺的耐药率为75.9%,头孢克洛、头孢呋辛及阿奇霉素耐药率分别为81.3%、41.1%及30.4%.头孢曲松、左氧氟沙星、氨苄西林/克拉维酸敏感率均高于95.0%.β-内酰胺酶阳性率为66.7%.检出1株BLNAR.结论流感嗜血杆菌在1岁以下的婴幼儿中感染率最高,并呈现明显的季节性变化.流感嗜血杆菌耐药机制复杂,产β-内酰胺酶率很高,仍然是流感嗜血杆菌的重要耐药机制.临床应根据药敏试验结果合理选用抗生素.

Cancer Therapy Using Antibiotics

Anticancer antibiotics have made a successful impact in the field of chemotherapeutics. For most of them, DNA is the molecular target. Some act as DNA intercalators or some prevent DNA repair among other mechanisms of actions, they are seen to have. The major disadvantages of these drugs though are the constant side effects and toxicities. With more focus on discovery of new drugs with newer scaffolds, the urge to discover and modify anticancer antibiotics is being lost. Modifications or even the wider research can yield newer better drugs for clinical use. The review here discusses the current antibiotic therapeutics, newer discoveries in the field as well ideas for future research.

兽医临床致病性大肠杆菌超广谱β-内酰胺酶的检测

超广谱β—内酰胺酶菌株在临床常显示多重耐药性,对兽医临床的用药带来很大的威胁。为指导临床合理用药,本文对猪鸡致病性大肠杆菌用双纸片协同法和分子生物学方法进行了超广谱β—内酰胺酶的检测。

绿脓杆菌耐药性与临床对策

绿脓杆菌属假单孢菌属,是临床感染的重要病原菌。研究表明,近年来由绿脓杆菌引起的感染呈上升趋势,且由于该菌对多种抗菌药物耐药性的存在,其治疗十分困难。目前,用于绿脓杆菌治疗的药物主要有β—内酰胺类(p—lactams)、氨基甙类(AGs)、氟喹诺酮类(FQs)和多粘菌素类(PMs)。

值得期待的新β内酰胺酶抑制剂阿维巴坦及其复合制剂

β内酰胺类抗生素是临床最为常用的抗菌药物。近10年世界范围内分离的肠杆菌科细菌、非发酵革兰阴性菌由于产超广谱β内酰胺酶（ESBLs）、AmpC酶和碳青霉烯酶（KPC），对青霉素类、头孢菌素类、β内酰胺酶抑制剂复方制剂乃至碳青霉烯类抗生素耐药现象严重。产KPC酶是目前肠杆菌科细菌对碳青霉烯类耐药的最主要原闪。产β内酰胺酶的细菌对如喹诺酮类、氨基糖苷类、多粘菌素、替加环素等其他类别抗菌药物亦町耐药，给治疗带来重大挑战[1-2]。

Antimicrobial Resistance and β-Lactamase Production among Hospital Dumpsite Isolates

Metallo-β-Lactamases (MBLs) and Extended Spectrum β-Lactamses (ESBLs) have emerged world-wide as a significant source of β-lactam resistance. The emergence of MBLs and ESBLs encoded on plasmids among Gram-negative pathogens in hospital dumpsites was investigated. Soils of different government and private hospitals were collected and processed following standard bacteriological techniques. Antimicrobial susceptibility testing was carried out by the disk-diffusion technique using Ceftazidime (30 μg), Cefuroxime (30 μg), Cefotaxime (30 μg), Cefixime (5 μg), Trimethprim-sulfamethoxazole (25 μg), Gentamycin (100 μg) Amoxicillin-Clavunalate (30 μg), Ciprofloxacin (5 μg), Ofloxacin (5 μg), Nitrofurantoin (300 μg) and Imipenem (10 μg). The role of plasmids in resistance was evaluated by subjecting isolates to curing using Sodium Dodecyl Sulfate (SDS). ESBLs production by Double-Disk Synergy Test (DDST) was carried out. Isolates resistant to Imipenem were subjected to a confirmatory test using Modified Hodge’s test and to MBLs production by DDST. Eighty-two Gram-negative isolates comprising of 32 (39.02%) Escherichia coli, 20 (24.39%) Serratia marcescens, 14 (17.07%) Klebsiella pneumonia, 10 (12.28%) Proteus mirabilis and 6 (7.32%) Enterobacter aerogenes were obtained. Susceptibility results revealed a 100% resistance of all isolates to Ceftazidime, Cefuroxime, Cefixime, Amoxycillin-clavulanate and Cefotaxime. A total of 66 (80.48%) isolates harboured plasmids out of which 26 (31.71%) isolates were ESBL producers. MBLs production was observed in 8 (25.00%) E. coli, 2 (2.41%) Klebsiella pneumonia and 2 (2.41%) Proteus mirabilis isolates. All MBLs producing isolates were ESBLs producers. The finding of highly resistant isolates producing ESBLs and MBLs in a hospital environment is quite disturbing and should be addressed urgently.

老年人下呼吸道感染细菌谱及抗生素耐药性监测

目的探讨老年人下呼吸道感染细菌谱及致病菌株对抗生素的耐药性。方法采用微量肉汤稀释法及双纸片法测定了154株致病菌对20种抗生素的敏感性,并进行耐甲氧西林葡萄球菌和产超广谱β-内酰胺酶(ESBLs)研究。结果革兰阳性菌34株,以凝固酶阴性葡萄球菌(50%)和金黄色葡萄球菌(26%)多见,万古霉素、利福平为最敏感。其中耐甲氧西林凝固酶阴性葡萄球菌(MRCNS)检出率占59%,耐甲氧西林金黄色葡萄球菌(MRSA)为(67%),对青霉素、苯唑青霉素的耐药率,对万古霉素的敏感性均为100%。革兰阴性菌120株,克雷伯菌属(29%)和大肠埃希氏菌(18%)常见,亚胺硫霉素、阿米卡星、头孢他啶的抗菌活性最强,覆盖率广。17株产ESBLs主要为克雷伯菌(58%)和大肠埃希氏菌(29%)。结论老年人下呼吸道感染的常见致病菌中MRSA,MRCNS和产ESBLs的比例很高。开展细菌药物敏感性监测,以强调临床合理使用抗生素。