Theoretical mechanistic study of the reaction of the methylidyne radical with methylacetylene

A detailed doublet potential energy surface for the reaction of CH with CH₃CCH is investigated at the B3LYP/6-311G(d,p) and G3B3 (single-point) levels. Various possible reaction pathways are probed. It is shown that the reaction is initiated by the addition of CH to the terminal C atom of CH₃CCH, forming CH₃CCHCH 1 (1a,1b). Starting from 1 (1a,1b), the most feasible pathway is the ring closure of 1a to CH₃–cCCHCH 2 followed by dissociation to P ₃ (CH₃–cCCCH+H), or a 2,3 H shift in 1a to form CH₃CHCCH 3 followed by C–H bond cleavage to form P ₅ (CH₂CHCCH+H), or a 1,2 H-shift in 1 (1a, 1b) to form CH₃CCCH₂ 4 followed by C–H bond fission to form P ₆ (CH₂CCCH₂+H). Much less competitively, 1 (1a,1b) can undergo 3,4 H shift to form CH₂CHCHCH 5. Subsequently, 5 can undergo either C–H bond cleavage to form P ₅ (CH₂CHCCH+H) or C–C bond cleavage to generate P ₇ (C₂H₂+C₂H₃). Our calculated results may represent the first mechanistic study of the CH + CH₃CCH reaction, and may thus lead to a deeper understanding of the title reaction.     

Formation Mechanism of the Free Radical Product and Its Precursor by the Reaction of Dehydro-L-ascorbic Acid with Amino Acid

During the formation of radical A (2) and its precursor (tris(2-deoxy-2-L-ascorbyl)amine, 1) by the reaction of dehydroascorbic acid (DHA) with amino acid, ascorbic acid (AsA) and the reduced red pigment (3) were newly identified, in addition to scorbamic acid (SCA) and the red pigment (4), as intermediate products. The addition of AsA to the DHA-amino acid reaction, as well as to the DHA-SCA reaction, greatly increased the formation of 3 and 1. The reaction of AsA with 4 gave rapidly 3, followed by the gradual production of 1. From these results, a reaction pathway is proposed that 3 formed by the reduction of 4 with AsA is a key intermediate and its condensation with DHA followed by reduction with AsA might produce 2 and 1.     

一株海洋真菌Aspergillus jensenii LW128的次级代谢产物及其抗菌活性研究

【目的】研究一株西北太平洋深海沉积物来源真菌Aspergillus jensenii LW128的次级代谢产物及其抗菌活性。【方法】利用硅胶柱色谱(silica gel column chromatography)、凝胶柱色谱(Sephadex LH-20 column chromatography)和反相高效液相色谱(reversed-phase high-performance liquid chromatography, RP-HPLC)等方法对菌株的发酵粗提物进行分离纯化得到单体化合物;将核磁共振波谱(nuclear magnetic resonance, NMR)、质谱(mass spectrometry, MS)数据与相关文献报道数据进行比对后确定化合物结构;采用肉汤微量稀释法测定化合物的抗菌活性。【结果】从海洋真菌Aspergillus jensenii LW128中分离并鉴定了10个已知化合物,分别为diorcinol D(1)、diorcinol K(2)、diorcinol I(3)、(+)-(7S)-7-O-methylsydonic acid (4)、(+)-s...     

Coronin7 forms a novel E3 ubiquitin ligase complex to promote the degradation of the anti-proliferative protein Tob

Tob belongs to the anti-proliferative Tob/BTG family. The level of Tob throughout the cell cycle is regulated by the SCF (Skp1/Cullin/F-box protein)^Skp2 ubiquitin ligase (E3) complex. Here, we show that Coronin7 (CRN7) is also involved in Tob degradation. We identified CRN7 as a Tob-interacting molecule. A sequence containing two of the six WD motifs in the middle of CRN7 was responsible for the interaction. CRN7 enhanced the polyubiquitination of Tob in vitro, and overexpression of CRN7 promoted proteasome-dependent degradation of Tob. Furthermore, CRN7 interacted with Cullin1 and Roc1 to form a novel SCF-like E3 complex, suggesting that Tob protein is regulated by multiple ubiquitination machineries.

Structured summary

Cullin1physically interacts with CRN7: shown by anti tag coimmunoprecipitation (view interaction)Roc1physically interacts with CRN7: shown by anti tag coimmunoprecipitation (view interaction)CRN7physically interacts with Tob1: shown by anti tag coimmunoprecipitation (view interaction)CDC34physically interacts with CRN7: shown by anti tag coimmunoprecipitation (view interaction)Tob1 and CRN7colocalize: shown by fluorescence microscopy (view interaction)Elongin Bphysically interacts with CRN7: shown by anti tag coimmunoprecipitation (view interaction)Elongin Cphysically interacts with CRN7: shown by anti tag coimmunoprecipitation (view interaction)Tob1physically interacts with CRN7: shown by two hybrid (view interaction)     

Nucleosides and Nucleotides. 192. Toward the Total Synthesis of Cyclic ADP-Carbocyclic-Ribose. Formation of the Intramolecular Pyrophosphate Linkage by a Conformation-Restriction Strategy in a Syn-form Using a Halogen Substitution at the 8-Position of the Adenine Ring

Abstract

The synthesis of cyclic ADP-carbocyclic-ribose (2), as a stable mimic for cyclic ADP-ribose, was investigated. Construction of the 18-membered backbone structure was successfully achieved by condensation of the two phosphate groups of 19, possibly due to restriction of the conformation of the substrate in a syn-form using an 8-chloro substituent at the adenine moiety. SN2 reactions between an optically active carbocyclic unit 8, which was constructed by a previously developed method, and 8-bromo-N ⁶-trichloroacetyl-2′,3′-O-isopropylideneadenosine 9c gave N-1-carbocyclic derivative, which was deprotected to give 5′,5′-diol derivatives 18. When 18 was treated with POCl₃ in PO(OEt)₃, the bromo group at the 8-position was replaced to give N-1-carbocyclic-8-chloroadenosine 5′,5′-diphosphate derivative 19 in 43% yield. Treatment of 19 with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride gave the desired intramolecular condensation product 20 in 10% yield. This is the first chemical construction of the 18-membered backbone structure containing an intramolecular pyrophosphate linkage of a cADPR-related compound with an adenine base.     

Books and the Child

Abstract

Jutta Ash (from a Crimm tale), RAPUNZEL, Holt, Rinehart & Winston: New York, 1982, unpaged, $10.95

Lorinda B. Cauley, THE GOOSE AND THE GOLDEN COINS, Harcourt Brace Jovanovich: New York, 1981, unpaged, $11.95 ($5.95 paper). Reviewed by Kenneth Marantz.

Graham Percy (adapted from Perrault), SLEEPING BEAUTY, Knopf: New York, 1980, unpaged, $1.75 (boards). Reviewed by Kenneth Marantz.

George Overlie (story by Pamela Espeland), THE STORY OF BAUCIS AND PHILOMON, Carolrhoda Books: Minneapolis, 1981, unpaged, n.p.i. Reviewed by Kenneth Marantz.

Michael Hague (retold by K. & M. Hague), THE MAN WHO KEPT HOUSE, Harcourt Brace Jovanovich: New York, 1981, unpaged, $11.95. Reviewed by Kenneth Marantz.

Donald Carrick, HARALD AND THE GIANT KNIGHT, Clarion Books: New York, 1982, unpaged, $10.95. Reviewed by Kenneth Marantz.

Annie Gusman (written by Arthur Crowley), THE WAGON MAN, Houghton Mifflin: Boston, 1981, unpaged, $8.95. Reviewed by Kenneth Marantz.

Diane Good (story by Louise Moeri), THE UNICORN AND THE PLOW, Dutton: New York, 1982, unpaged, $8.95. Reviewed by Kenneth Marantz.

Victoria Chess (story by Larry Bograd), LOST IN THE STORE, Macmillan: New York, 1981, unpaged, $8.95. Reviewed by Kenneth Marantz.

Edward Gorey (story by Florence P. Heide), TREEHORN'S TREASURE, Holiday House: New York, 1981, unpaged, $7.95. Reviewed by Kenneth Marantz.

Ernest Goldstein, EDWARD HICKS: THE PEACEABLE KINGDOM and WINSLOW HOMER: THE GULF STREAM, Garrard Publishers: Champaign, Illinois, 1982, 48 pages, $8.95 (each) from the “Let's Get Lost in a Painting” series. Reviewed by Kenneth Marantz.     

Studies on the Later Stage of the Biosynthesis of Pleuromutilin

Mutilin (4) and deoxy analogues 2 and 3 are biosynthetic precursors of pleuromutilin (1) in the later stage of biosynthesis. Precursors 2 and 3 are required for studies on the oxygenation steps in biosynthesis, and were synthesized from readily available 1 via 4 by deoxygenation of the hydroxy groups. Feeding experiments with the ²H-labeled precursors confirmed their microbial conversion into 1.     

中国医院住院患者体验和满意监测量表的开发研究：量表的初步形成

目的 开发适合中国医院应用的住院患者体验与满意监测量表。方法 通过检索国内外的相关文献,收集国外成熟的满意度量表,结合国内现有的量表,通过专家组对条目进行筛选并修正。结果 研制出的CHPESM量表包含可及入院、一般住院服务、治疗服务、意见管理、环境与后勤以及出院指导6个维度28个核心条目,均采用Likert 5级评分法。结论 CHPESM量表具有较好的内容效度。     

苦槛蓝叶中的黄酮类化合物

为了解苦槛蓝(Myoporum bontioides A.Gray)的化学成分,采用色谱分离技术从苦槛蓝叶片中分离得到11个黄酮类化合物。通过波谱分析,他们的结构分别鉴定为:桔皮素(1)、甜橙素(2)、5,4′-二羟基-6,7,8,3′-四甲氧基黄酮(3)、4′,5,7,8-四甲氧基黄酮(4)、去甲基川陈皮素(5)、5-羟基-6,7,3′,4′-四甲氧基黄酮(6)、3′,4′,5,6,7,8-六甲氧基黄酮(7)、二氢山柰酚(8)、木犀草素(9)、3′,4′,5,7-四羟基-3-甲氧基黄酮(10)和芹黄素(11)。除化合物9之外,其他化合物均为首次从苦槛蓝叶片中分离得到。孢子萌发法测定结果表明,化合物1,2,8和9对香蕉炭疽菌(Colletotrichum musae)具有较好的抑菌活性。这为苦槛蓝叶片中有效成分的利用提供了理论依据。     

Method for the Synthesis of Uric Acid Derivatives

Abstract

A general procedure to obtain tetra-substituted uric acid by stepwise N-alkylation is described. 2,6-Dichloropurine (1) was condensed with 1-propanol by Mitsunobu reaction to give 9-propyl congener (2). Treatment of 2 with ammonia gave adenine derivative (4a), which was converted to the 8-oxoadenine (5b) in 3 steps. Methylation of 5b proceeded site-specifically to give 6-amino-2-chloro-7,8-dihydro-7-methyl-9-propylpurin-8-one (6) as a sole product. Compound 6 was successively treated with NaNO₂ and iodomethane to give 2-chloro-1,6,7,8-tetrahydro-1,7-dimethyl-9-propylpurin-6,8-dione (9) accompanied by the O ⁶-methyl product (8) in 75% and 6.9%, respectively. After nucleophilic substitution of 9 with NaOAc, the product (11) was reacted with iodomethane to give the uric acid (12) and the 2-methoxy product (13) in 46% and 15.5%, respectively. However, the reaction of 11 with the benzylating agents gave only O-benzyl products (14a,b).     

Art in the Making

Abstract

There's Pigs and Pigs: Erik Blegvad, The Three Little Pigs, Atheneum: New York, 1980, 32 pages, $8.95.

There's Pigs and Pigs: Joseph Jacobs, The Story of the Three Little Pigs (illust. by Lorinda B. Cauley), Putnam: New York, 1980, unpaged, $8.95.

There's Pigs and Pigs: Margaret Wise Brown (illust. by Ann Strugnell), Once Upon a Time in a Pigpen, Addison-Wesley: Reading, Mass., 1980, 64 pages, $10.95.

There's Pigs and Pigs: Miska Miles (illust. by Leslie Morrill), This Little Pig, Dutton: New York, 1980, unpaged, $6.95.

Picture Books: William Steig, Gorky Rising, Farrar, Strauss &; Giroux: New York, 1980, unpaged, $10.95.

Picture Books: Charles Keeping, Willie's Fire-Engine, Oxford University: New York, 1980, unpaged, $10.95 (boards).

Picture Books: Lydia Pender (illust. by Judith Cowell), The Useless Donkeys, Warne: New York, 1979, unpaged, $9.95.

Picture Books: Lillie D. Chaffin (illust. by Lloyd Bloom), We Be Warm Till Springtime Comes, Macmillan: New York, 1980, unpaged, $9.95.

Picture Books: Kate Canning, A Painted Tale, Barrons: Woodbury, N.Y.: 1979, unpaged, $6.95 (boards).

Historical Explorations: Maurice Boutet de Monvel, Joan of Arc, Viking: New York, 1980, 55 pages, $12.95.

Historical Explorations: Mitsumasa, Anno, Anno's Medieval World, Philomel Books: New York, 1980, 48 pages, $9.99.

Historical Explorations: Peter Spier, People, Doubleday: New York, 1980, unpaged, $10.00.

Historical Explorations: John S. Goodall, An Edwardian Season, Atheneum: New York, 1980, unpaged, $7.95.

Historical Explorations: Miriam Schlein (illust. by Erik Hilgert), I, Tut, Four Winds Press: New York, 1979, unpaged, $7.95.     

Temperature-dependence of enantioselectivity and desymmetrization in the acetylation of 2-mono- and 2,2-di-substituted 1,3-propanediols by a novel lipase isolated from the yeast Cryptococcus spp. S-2

The effect of temperature on enantioselectivity and desymmetrization in the acetylation of 2-phenyl-1,3-propanediol (1a), 2-benzyl-1,3-propanediol (1b), 2-methyl-2-phenyl-1,3-propanediol (1c) and 2-benzyl-2-methyl-1,3-propanediol (1d) by a novel lipase (CSL) isolated from the yeast Cryptococcus spp. S-2 was studied. Desymmetrization of 1a, 1c and 1d by CSL-catalyzed acetylation was observed in the temperature range of ?20°C to 40°C, while diacetylation of 1b occurred considerably even at 0°C. The kinetic parameters of the selectivity indicated that the acetylation of 1a is an entropy controlled process whereas the reaction of 1c and 1d is mainly controlled by the enthalpy term. In the monoacetylation of the diol 1d, the preferred configuration in the enantiomeric induction by CSL was opposite to that of immobilized porcine pancreatic lipase (PPL).     

A Convenient Method for the Synthesis of 2-(β-D-Glycopyranosylthio) Pyridines

Abstract

Treatment of piperidinium salts of dihydropyridinethiolates 3 with glycosyl bromides 4 in dry acetone provides a convenient and high yielding synthesis of 1,4-dihydro-3-cyanopyridine thioglycosides 5. The structures of 5 were confirmed by oxidation as well as by ¹H NMR and ¹³C NMR spectral analysis.     

JL-DRGs在综合医院管理中的应用探讨

目的 探讨JL-DRGs在综合医院管理中的应用。方法 对2012年和2013年运行JL-DRGs管理前后的全部出院病例进行统计分析。结果 2013年开始全面运行JL-DRGs后平均住院日下降17.74%,均次费用下降13.49%,医保超支年度累计减少1 866万元,平均每月医保超支额度下降39.23%,医疗质量、效率均显著提升。结论 JL-DRGs在大型综合医院管理中应用效果好,可以积极促进医院提质升效并降低运营成本。     

An adjacent arginine, and the phosphorylated tyrosine in the c-Met receptor target sequence, dictates the orientation of c-Cbl binding

Previously, we have demonstrated that the tyrosine phosphorylated hepatocyte growth factor receptor (Met) binds to the c-Cbl phosphotyrosine-recognition, tyrosine kinase binding (TKB) domain in a reverse orientation compared to other c-Cbl binding partners. A Met peptide with the DpYR motif changed to RpYD (MetRD) retains a similar TKB binding affinity as the native Met peptide. However, the TKB: MetRD complex crystal structure reveals a complete reversal of the binding orientation. Collated data indicates that both binding and orientation is dictated by the phosphorylated tyrosine and an adjacent arginine forming intra-peptide hydrogen bonds and aligning unidirectionally with complementary charges in the phosphotyrosine binding pocket of c-Cbl.

Structured summary

c-Cbl and MetRDbind: shown by x-ray crystallography (view interaction)c-Cbl and MetRDbind: shown by mass spectrometry studies of complexes (view interaction)c-Cblbind to Met: shown by surface plasmon resonance (view interactions 1,2)     

Characterization of 2,4-D Binding to the Auxin-binding Protein Purified from Etiolated Mung Bean Seedlings

New acetylenic nematicidal compound, penipratynolene (1), methy (2′R)-4-(2′-hydroxy-3′-butynoxy)benzoate, together with two known compounds, 6-methoxycarbonylpicolinic acid (2) and 2,6-pyridinedicarboxylic acid (3), were isolated from the culture filtrate of Penicillium bilaiae Chalabuda. The structures of 1–3 were established by spectroscopic methods. The absolute configuration of 1 was confirmed by using a modified version of Mosher’s method. Compounds 1–3 showed nematicidal activity of 77%, 52%, and 98%, respectively, by a bioassay at 300 mg/l with the root-lesion nematode Pratylenchus penetrans.     

Synthesis of the Fluoromethyl Derivatives of Carbocyclic Oxetanocin A

Abstract

Treatment of the 2,3-di-O-benzoate 1 with sodium boronhydride mainly afforded the 3-O-benzoate 2 accompanied with isomers 3a,b and fully deprotected product 4. Compound 2 was converted to 5, from which 8 was obtained. The 1-cyclobutanols 8 and 5 were successfully condensed with 6-chloropurine by Mitsunobu reaction to give 9 and 11, respectively. After partial deprotection, the cyclobutyl nucleosides 10 and 15 were subjected to fluorination using DAST to afford the fluoromethyl analogs 12 and 16 from which target compounds 14 and 17 were obtained in good yields, respectively.

     

Books and the Child

Abstract

Jindra Capek (story by Max Bolliger), The Most Beautiful Song, Little, Brown: Boston, 1980, unpaged, $8.95 (boards)

Maurice Sendak, Outside Over There, Harper &; Row: New York, 1981, unpaged, $12.95

Chris van Allsburg, Jumanji, Houghton Mifflin: Boston, Mass., 1981, unpaged, $9.95

Anita Lobel (words by Arnold Lobel), On Market Street, Greenwillow: New York, 1981, unpaged, $8.95

Stephen Gammell (story by Olaf Baker), Where The Buffaloes Begin, Warne: New York, 1981, unpaged, $8.95

Nicola Bayley and William Mayne, The Patchwork Cat, Knopf: New York, 1981, unpaged, $8.95 (boards)

Jan Brett, Fritz and the Beautiful Horses, Houghton Mifflin: Boston, 1981, 32 pages, $8.95

Guy Billout, Thunderbolt and Rainbow: A Look at Greek Mythology, Prentice-Hall: Englewood Cliffs, N.J., 1981, unpaged, $9.95 (boards)

Michael Foreman, Trick a Tracker, Philomel Books: New York, 1981, unpaged, $9.99

Monika Beisner (text by Alison Lurie), Fabulous Beasts, Farrar, Straus &; Giroux: New York, 1981, unpaged, $9.95

Leonard Baskin (words by the Baskin family), Hosie's Zoo, Viking: New York, 1981, unpaged, $10.95     

An interaction between human Sec63 and nucleoredoxin may provide the missing link between the SEC63 gene and polycystic liver disease

The formation of multiple cysts in one or several organs is a characteristic of several human inherited diseases. Recent research suggests that problems in planar cell polarity may be the common denominator in polycystic diseases. Mutations in at least two genes are linked to autosomal dominant polycystic liver disease (PCLD), PRKCSH and SEC63. A recent study linked PRKCSH to the signaling- and cytoskeletal adaptor-component β-catenin. In a yeast two hybrid screen we identified the cytosolic protein nucleoredoxin (NRX) as an interaction partner of human Sec63. Since NRX is involved in the Wnt signaling pathways, we characterized this interaction. Thus, Sec63 is linked to the Wnt signaling pathways and this interaction may be the reason why mutations in SEC63 can lead to PCLD.

Structured summary

Sec63physically interacts with NRX by two hybrid(View interaction)NRXbinds to Sec63 by peptide array (View Interaction 1, 2)Sec63binds to NRX by pull down(View interaction)Sec63binds to NRX by peptide array (View Interaction 1, 2, 3)