Tandem Manner Research Articles

Regioselective synthesis of 3-heteroarylpiperidin-2-ones and diazacyclopenta[ a]phenalenone via carbenoid reactions

Rhodium(II) catalyzed carbenoid reactions of 3-diazopiperidin-2-ones were carried out with indoles and pyrroles to afford the respective (3-indol-3-yl)- and (3-pyrrol-2-yl)piperidones with regioselectivity. Interestingly, the reaction of bis-diazoimide in the presence of Rh 2(OAc) 4 catalyst furnished diazacyclopenta[ a]phenalenone in a tandem manner.

Solid‐Supported Microwave‐Accelerated Intramolecular Knoevenagel Hetero‐Diels—Alder Reactions: A Protocol for the Synthesis of Indolo[2,1‐a]pyrrolo[4′,3′:4,5]pyran Ring Systems.

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Solid-Supported Microwave-Accelerated Intramolecular Knoevenagel ­Hetero-Diels-Alder Reactions: A Protocol for the Synthesis of Indolo[2,1-a]pyrrolo[4′,3′:4,5]pyran Ring Systems

A novel and mild method was established to synthesize pyrroloindole derivatives. This method entails an ethylenediammonium diacetate (EDDA)-promoted Knoevenagel condensation of various diones with appropriately substituted aldehydes to yield the arylidene intermediate, which was smoothly converted to the final products by intramolecular Diels-Alder reaction in a tandem manner. This process describes a practical synthetic method to prepare pyrroloindole derivatives.

N-H Carbazole Synthesis from 2-Chloroanilines via Consecutive Amination and C−H Activation

N-H carbazoles can be produced from 2-chloroanilines and aryl bromides via consecutive catalytic amination and C-H activation. In many instances, this can be done in a tandem manner in one pot. The methodologies developed can be used in the synthesis of a range of carbazoles, including the natural products Clausine P and glycozolidine and a precursor in the synthesis of Clausines H, K, O, and 7-methoxy-O-methylmukonal, and can be extended to the synthesis of indoles.

Multicomponent Reactions of Diazoamides: Diastereoselective Synthesis of Mono‐ and Bis‐spirofurooxindoles.

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Multicomponent reactions of diazoamides: diastereoselective synthesis of mono- and bis-spirofurooxindoles.

This paper describes the intermolecular generation of carbonyl ylides by dirhodium(II) tetraacetate-catalyzed reaction of 3-diazoindol-2-ones in the presence of aryl aldehydes and heteroaryl aldehydes. These carbonyl ylides were subsequently trapped with dipolarophiles such as dimethyl acetylenedicarboxylate, maleic anhydride, and ethyl acrylate to afford spirofurooxindoles. Consequently, diastereoselective synthesis of spirodihydrofurooxindoles through the multicomponent reactions of cyclic diazoamides was successfully achieved for the first time. The stereochemistry of the spirofurooxindole is unequivocally corroborated by the single-crystal X-ray analysis of the representative product 4o. Interestingly, these reactions were extended to double multicomponent reactions of bis-cyclic diazoamides to afford the respective complex polycycles in a tandem manner, which led to the construction of four carbon-carbon bonds, two carbon-oxygen bonds, and four chiral centers in a single synthetic step.

Genes for an alkaline D-stereospecific endopeptidase and its homolog are located in tandem on Bacillus cereus genome

Alkaline D-peptidase (Adp) from Bacillus cereus DF4-B is a D-stereospecific endopeptidase acting on oligopeptides composed of D-phenylalanine and the primary structure deduced from its gene, adp, shows a similarity with D-stereospecific hydrolases from Ochrobactrum anthropi strains. We have isolated DNA fragments covering the flanking region of adp from DF4-B genome and found an additional gene, adp2, located upstream of adp. The deduced amino acid sequence of Adp2 showed 96% and 85% identity with those of Adp from B. cereus strains AH559 and DF4-B, respectively. The recombinant Adp2 expressed in Escherichia coli was purified to homogeneity and characterized. It had hydrolyzing activity toward ( D-Phe) 3, ( D-Phe) 4, and ( D-Phe) 6 but did not act on ( L-Phe) 4, D-Phe-NH 2, and L-Phe-NH 2, some characteristics that are closely related to those of Adp from strain DF4-B. These results indicate that highly homologous genes encoding D-stereospecific endopeptidases are arranged in a tandem manner on the genomic DNA of B. cereus DF4-B.

Construction of Fused Cyclooctanoid Ring Systems via Seven-Membered Ring Carbonyl Ylides

Abstract A series of α-diazo carbonyl compounds tethered to cyclopentanone/cyclohexanone/1-tetralone units have been synthesized using a diazomethane solution to construct various fused cyclooctane ring systems via rhodium-generated carbonyl ylides. The reaction of rhodium(II) acetate dimer with various α-diazo carbonyl compounds generated transient cyclic seven-membered ring carbonyl ylides, which underwent facile 1,3-dipolar cycloadditions with dipolarophiles, like N-phenylmaleimide, p-benzoquinone, and DMAD to furnish a variety of fused epoxy-bridged cyclooctane ring systems in a tandem manner. Interestingly, an oxepine ring system was generated via an intramolecular proton transfer of a seven-membered ring carbonyl ylide. A tri-oxa polycyclic compound was obtained in the case of p-benzoquinone as dipolarophile. A single-crystal X-ray analysis of a fused cyclootanoid derivative is reported to decisively establish the structure and stereochemistry of the fused epoxy-bridged cyclooctane ring systems; a further analysis revealed the existence of a unique intermolecular C–H···π interaction motif in the solid-state architecture.

Tandem oligonucleotide synthesis on solid-phase supports for the production of multiple oligonucleotides.

More than one oligonucleotide can be synthesized at a time by linking multiple oligonucleotides end-to-end in a tandem manner on the surface of a solid-phase support. The 5'-terminal hydroxyl position of one oligonucleotide serves as the starting point for the next oligonucleotide synthesis. The two oligonucleotides are linked via a cleavable 3'-O-hydroquinone-O,O'-diacetic acid linker arm (Q-linker). The Q-linker is rapidly and efficiently coupled to the 5'-OH position of immobilized oligonucleotides using HATU, HBTU, or HCTU in the presence of 1 equiv of DMAP. This protocol avoids introduction of phosphate linkages on either the 3'- or 5'-end of oligonucleotides. A single NH(4)OH cleavage step can simultaneously release the products from the surface of the support and each other to produce free 5'- and 3'-hydroxyl termini. Selective cleavage of one oligonucleotide out of two sequences has also been accomplished via a combination of succinyl and Q-linker linker arms. Tandem synthesis of multiple oligonucleotides is useful for producing sets of primers for PCR, DNA sequencing, and other diagnostic applications as well as double-stranded oligonucleotides. Tandem synthesis of the same sequence multiple times increases the yield of material from any single synthesis column for maximum economy in large-scale synthesis. This method can also be combined with reusable solid-phase supports to further reduce the cost of oligonucleotide production.

Molecular characterization of KMP11 from Trypanosoma cruzi: a cytoskeleton-associated protein regulated at the translational level.

Kinetoplasmid membrane protein-11 (KMP11) is present in a wide range of trypanosomatids. In the present paper, we show that the T. cruzi KMP11 gene is organized in a cluster formed by four gene units arranged in a head-to-tail tandem manner located on a chromosome of about 1900 kb. Northern blot analyses indicated that the steady-state level of mature KMP11 transcripts of 0.52 kb is high and similar in the three forms of the parasite. The KMP11 mRNAs have a half-life of about 16 h whose steady-state level is strongly downregulated when the parasites reach the stationary growth phase. The T. cruzi KMP11 sequence presents a significant homology with the amino-terminal third of the cytoskeleton-associated protein CIP1 from Arabidopsis thaliana. Western blot and immunoelectron microscopy studies showed that KMP11 is present in the cytoskeleton structure. Because the strong downregulation observed in the de novo synthesis of KMP11 protein in parasites treated with vinblastine is not accompanied by a significant fall in the steady-state level of KMP11 mRNAs, regulatory control of the protein at the translational level is suggested.

Core-stabilized polymeric micelle as potential drug carrier: increased solubilization of taxol

Poly(ethylene glycol-b-lactide) possessing a methoxy group at the poly(ethylene glycol) (PEG) chain end and a polymerizable methacryloyl group at the poly(lactic acid) (PLA) chain end (MeO–PEG/PLA–methacryloyl) was prepared by an anionic ring-opening polymerization of ethylene oxide and DL-lactide in tandem manner initiated with a potassium 2-methoxyethanolate, followed by end-capping with an excess of methacrylic anhydride. The molecular weight of the obtained polymer was controlled by the initial monomer/initiator ratio, which was confirmed by the combination of gel permeation chromatography and nuclear magnetic resonance analyses. The functionality of the methacryloyl–PLA end was almost quantitative. The MeO–PEG/PLA–methacryloyl (38/35; these numbers in parentheses denote the molecular weights of PEG and PLA segments divided by 100, respectively) formed a core–shell type spherical micelle in aqueous media obtained by a dialysis technique, the cumulant diameter of which was ca. 30 nm with very low polydispersity factor. The methacryloyl group adjacent to the PLA was polymerized in the PLA core of the micelle. The polymerization proceeded thermally with radical initiator and photochemically with photo-initiator to produce core-polymerized nanoparticles, which was found by spectroscopic and light-scattering techniques. Taxol-incorporated micelles were prepared to entrap Taxol into MeO–PEG/PLA–methyacryloyl block copolymer micelles by the oil/water emulsion method. Copyright © 1999 John Wiley & Sons, Ltd.

Coupled 3-D kinetics thermal-hydraulic analysis of Hot Zero Power main steam line breaks using RETRAN and STAR codes

The Main Steam Line Break (MSLB) at End of Life (EOL), Hot Zero Power (HZP) conditions accident was analyzed using a fully time-dependent coupled thermal-hydraulic (T/H) and neutronics method, and compared against conservative Final Safety Analysis Report (FSAR) results, which predict a return-to-power. The development and improvement of coupled neutronics/T/H analysis techniques provide many advantages including the capability to evaluate the impact of modeling assumptions made in previous reactor kinetics and T/H calculations. The coupled STAR kinetics and RETRAN T/H technique developed here provides a means to evaluate the quasi-static, point kinetics approximation against a fully time-dependent, three-dimensional approach. Using the state-of-the-art 3-D STAR reactor kinetics code with the RETRAN reactor coolant system (RCS) T/H code in a best-estimate approach, it is now possible to evaluate the impact on safety margins imposed by conservative FSAR MSLB assumptions. The method presented shows how the time-dependent 3-D STAR nodal code model was used directly with core inlet conditions determined by RETRAN for a Westinghouse PWR. The STAR/RETRAN results clearly demonstrate that a return-to-power is NOT predicted when a 3-D thermal-hydraulically coupled time-dependent kinetics approach is used. This study shows that: (a) quasi-static and point kinetics methods are not able to describe severe PWR asymmetric transient phenomena adequately; and (b) fully coupled, 3-D time-dependent analysis methods should be used for PWR reactor transients instead. By coupling the RCS response in terms of updated core inlet conditions with 3-D time-dependent core kinetics response, in a tandem manner, the core power and T/H RCS conditions are forced to be self-consistent during the entire event, when non-equilibrium conditions exist.

Herpes simplex virus-induced “Rolling circle” amplification of SV40 DNA sequences in a transformed hamster cell line correlates with tandem integration of the SV40 genome

Infection with herpes simplex virus leads to amplification of SV40 DNA in various SV40-transformed cells. In earlier studies with the SV40-transformed hamster cell line Elona two different types of DNA amplification could be identified: (i) Bidirectional overreplication of chromosomally integrated SV40 DNA expanding into the flanking cellular sequences (“onion skin” type) and (ii) highly efficient synthesis of extremely large head-to-tail concatemers containing exclusively SV40 DNA (“rolling circle” type). These investigations have indicated that the chromosomally integrated form of SV40 might be the substrate for both types of overreplication. There still had been uncertainties as to whether and how these events were connected. A hypothetical assumption of a recombinational event leading to the excision of SV40 DNA molecules is supported by the results presented here: In this study cloned Elona cell lines were investigated for their ability to amplify SV40 sequences and for the mechanism of amplification utilized. SV40 integration in a partial tandem manner correlates with a strong rolling circle amplification. In contrast, in one cell line harboring a truncated SV40 genome, amplification appears mainly restricted to intrachromosomal bidirectional overreplication. Possible implications for HSV functions involved in the amplification process will be discussed.

巨大内頸-眼動脈瘤治療の問題点

Direct clipping was performed in two cases of giant ophthalmic (30mm in diameter, subopticochiasmal global type) aneurysms in the right side who presented with visual disturbances in both eyes. Case 2 showed a second small aneurysm in the left IC-ophthalmic region. Preoperatively collateral circulation and tolerance to ischemia were studied by the Allcock and Matas tests. Both cases were operated on by right frontotemporal craniotomy. The neck carotid arteries were prepared for temporary occlusion during which time the brain function was monitored by scalp EEG. An STA-MCA anastomosis was performed before aneurysm surgery in Case 2.The optic canal was opened and the anterior clinoid processes, which were well developed and pneumatized in both cases, were meticulously removed subdurally with an air drill. The anterior clinoid process in Case 1 continued to the middle clinoid process forming a bony canal around C3, which made the situation even more difficult. The cavernous sinus had to be opened around C3 in both cases in order to obtain space for the clip blade in the proximal neck of the aneurysm. Further dissection of the aneurysm from the surrounding structures such as the contralateral IC, optic nerve and chiasm could only proceed after the aneurysm had been decompressed by puncture, after which fenestrated clips could be applied without difficulty. Only one fenestrated and angled clip was applied in Case 1. Three fenestrated clips were needed in tandem manner in order to close the neck in Case 2. Here a fourth straight clip was necessary in order to stop continuous oozing, probably from the space between the tandem clips.Postoperatively Case 1 returned to her normal household activities. Case 2 was blinded in her right eye and showed dense left hemiparesis, for which she is receiving rehabilitation at four months after the surgery. CT showed an infarction in the territory of the right anterior choroidal artery.Discussions are presented about 1) choice of treatment, direct or IC occlusion with bypass surgery; 2) ischemia monitors and brain protection during temporary occlusion of the IC; 3) importance of opening the cavernous sinus in order to obtain the proximal neck of the aneurysm; 4) importance of protection of the posterior communicating, anterior choroidal and perforating arteries, especially when fenestrated and angled clips are applied.

Characterization of a highly repetitive sequence DNA family in rat

A 92 to 93 base-pair highly reiterated DNA from rat liver has been isolated by digestion with EcoRI and cloned in pBR322. Three recombinant plasmids have been studied in detail; these are p93-2 and p93-10, both of which contain two 93 base-pair inserts, and p93-15, which contains one 92 base-pair and two 93 base-pair inserts. Analysis of these seven cloned DNA fragments reveals that 93 base-pair highly repetitive DNA exhibits as much as 50% overall sequence heterogeneity although several families can be identified on the basis of a high degree of sequence homology among particular cloned inserts. Individual families have also been identified on the basis of specific restriction endonuclease sites. This property, coupled with a limited degree of cross-hybridization among the groups of inserts in filter hybridizations, has been utilized to demonstrate that the three 93(2) base-pair families identified here are repeated in a regularly interspersed, tandem manner with each family repeated no more frequently than once every fourth sequence. Similar conclusions have been reached by analysis of a specific fraction of 370 base-pair rat repeated DNA (Pech et al., 1979 a). The chromosomal location of these 93 base-pair repeated sequences has been determined by in situ hybridization. They are found primarily, though not exclusively, at centromeres and telomeres of metaphase chromosomes. Highly reiterated 93 base-pair DNA is transcribed in HTC cells. Large RNA transcripts containing sequences homologous to 93 base-pair DNA have been identified in HTC cell nuclei utilizing the RNA-DNA filter hybridization technology of Alwine et al., (1977).

The Capacity of The Soaking Pit-Rolling Mill Complex in Steel Production

AbstractThis paper considers a problem in the production of steel at the Hilton Works of Stelco in Hamilton, Ontario. The necessity of having uniformly hot steel, provided by a battery of soaking pits, limits the production capacity of a rolling mill. At times there is nohot steel and the mill comes into “nothiag hot” delays.The obvious approach is to consider the soaking pits as parallel servers feeding the mill in a tandem manner. However, a more fruitful approach is to consider the pits as units circulating a cyclic queue. Clos dform solutions are found for the capacity of the pit-mill complex which take into accountthe individual heating rates of each pit as well as the possible necessity of repairs.