bluuebunny/crossref_metadata_2025 huggingface dataset:
Direkte Bestimmung der konjugativen und hyperkonjugativen Stabilisierung in Diinen, Dienen und verwandten Verbindungen
Authors: Cappel Daniel , Tüllmann Sandor , Krapp Andreas , Frenking Gernot
Published: May 2005

Die intrinsische Stärke der Konjugation und Hyperkonjugation in 1,3‐Butadien, 1,3‐Butadiin und verwandten Verbindungen wurde durch Energiedekompositionsanalyse bestimmt. Die Rechnungen ergeben, dass die π‐Konjugation im 1,3‐Butadiin etwa doppelt so stark ist wie im 1,3‐Butadien und dass die hyperkonjugativen π‐π*‐Wechselwirkungen von C‐H‐ und C‐C‐Bindungen mit C‐C‐Mehrfachbindungen etwa halb so stark sind wie die π‐Konjugation zwischen Mehrfachbindungen.
Direct Estimate of the Conjugative and Hyperconjugative Stabilization in Diynes, Dienes, and Related Compounds
Authors: Cappel Daniel , Tüllmann Sandor , Krapp Andreas , Frenking Gernot
Published: May 2005

The intrinsic strength of the conjugation and hyperconjugation in 1,3‐butadiene, 1,3‐butadiyne, and related compounds was determined by energy decomposition analysis. The calculations indicate that the π conjugation in 1,3‐butadiyne is roughly twice as strong as that in 1,3‐butadiene, and that the hyperconjugative interactions of CH and CC bonds with CC multiple bonds are about half as strong as the π conjugation between multiple bonds.
The stabilizing contribution of thymine in duplexes of (dA)24 with (dU)24, (dT)24, (dU12–dT12), (dU–dT)12, (dU2–dT2)6, or (dU3–dT3)4: Nearest neighbor and next‐nearest neighbor effects
Authors: Howard Frank B.
Published: May 2005

Ultraviolet melting curves are used to determine the effect of the pyrimidine 5‐methyl group on the stability of duplexes of (dA)24 with (dU)24, (dT)24, (dU12–dT12), (dU–dT)12, (dU2–dT2)6, and (dU3–dT3)4. Substitution of a T for a U results in an increase in stability, which is attributed to an increase in strength of dipole‐induced dipole and dispersion (van der Waals) interactions. Significant additional enhancement occurs when two T residues are adjacent. A further increase in the number of adjacent T's has a relatively slight effect on Tm. The sequence effect appears to be largely attributable to an increment in dispersion forces.

The CD spectra of the duplexes are all closely similar except in the region between 260 and 290 nm. A band near 272 nm associated with the presence of U in the spectrum of (dA)24·(dU)24 decreases in intensity when T's are incorporated in the pyrimidine strand. The band is completely replaced in the spectrum of (dA)24·(dT)24 with a new maximum at 282 nm and a minimum at 268 nm, both of lower magnitude. The emergence of the two new bands is correlated with the presence of adjacent T's once more, and only two adjacent T's appear necessary for a major part of the change to occur.

The degree of cation release on thermal dissociation of the oligomer dimers ranges from Δi = 0.14 to 0.16, about the same or slightly less than values reported for polynucleotide duplexes and less than predicted from theoretical calculations. © 2005 Wiley Periodicals, Inc. Biopolymers 78:221–229, 2005
Multiplex‐PCR‐Based Recombination as a Novel High‐Fidelity Method for Directed Evolution
Authors: Eggert Thorsten , Funke Susanne Aileen , Rao Nalam M. , Acharya Priyamvada , Krumm Holger , Reetz Manfred T. , Jaeger Karl‐Erich
Published: May 2005

A new and convenient method for the in vitro recombination of single point mutations is presented. This method efficiently reduces the introduction of novel point mutations, which usually occur during recombination processes. A multiplex polymerase chain reaction (multiplex‐PCR) generates gene fragments that contain preformed point mutations. These fragments are subsequently assembled into full‐length genes by a recombination‐PCR step. The process of multiplex‐PCR‐based recombination (MUPREC) does not require DNase I digestion for gene‐fragmentation and is therefore easy to perform, even with small amounts of target DNA. The protocol yields high frequencies of recombination without creating a wild‐type background. Furthermore, the low error rate results in high‐quality variant libraries of true recombinants, thereby minimizing the screening efforts and saving time and money. The MUPREC method was used in the directed evolution of a Bacillus subtilis lipase that can catalyse the enantioselective hydrolysis of a model meso‐compound. Thereby, the method was proved to be useful in producing a reliable second‐generation library of true recombinants from which better performing variants were identified by using a high‐throughput electrospray ionization mass spectrometry (ESI‐MS) screening system.
Utilizing the Power of Microbial Genetics to Bridge the Gap Between the Promise and the Application of Marine Natural Products
Authors: Fortman J. L. , Sherman David H.
Published: May 2005

Marine organisms are a rich source of secondary metabolites. They have yielded thousands of compounds with a broad range of biomedical applications. Thus far, samples required for preclinical and clinical studies have been obtained by collection from the wild, by mariculture, and by total chemical synthesis. However, for a number of complex marine metabolites, none of these options is feasible for either economic or environmental reasons. In order to proceed with the development of many of these promising therapeutic compounds, a reliable and renewable source must be found. Over the last twenty years, the study of microbial secondary metabolites has greatly advanced our understanding of how nature utilizes simple starting materials to yield complex small molecules. Much of this work has focused on polyketides and nonribosomal peptides, two classes of molecules that are prevalent in marine micro‐ and macroorganisms. The lessons learned from the study of terrestrial metabolite biosynthesis are now being applied to the marine world. As techniques for cloning and heterologous expression of biosynthetic pathways continue to improve, they may provide our greatest hope for bridging the gap between the promise and application of many marine natural products.
Highly Diastereoselective and Enantioselective Preparation of Homoallylic Amines: Application for the Synthesis of β‐Amino Acids and γ‐Lactams
Authors: Ramachandran P. Veeraraghavan , Burghardt Thomas E.
Published: May 2005

Reactions of N‐silyl‐ and N‐aluminoimines with B‐allyldiisopinocampheylborane in the presence of methanol, followed by oxidative workup furnished homoallylic amines in good yields and high ee. A 11B NMR spectroscopy study revealed that the reactions do not proceed, even at room temperature, unless a molar equivalent of water or methanol is added. The first reagent‐controlled asymmetric crotylboration and alkoxyallylboration of aldimines furnishing β‐methyl or β‐alkoxy homoallylic amines in very high diastereoselectivity and enantioselectivity are reported herein. Crotylboration and alkoxyallylboration of imines proceed only with the “allyl”‐boron “ate” complexes, instead of the “allyl”‐dialkylboron reagents used with aldehydes. The addition of methanol is necessary for these reactions as well. Application of this methodology for the conversion of representative nitriles to β‐amino acids in two steps has been described. Additionally, a procedure for the preparation of chiral δ‐amino alcohols and γ‐lactams from nitriles is also reported.
G–G Base‐Pairing in Nucleobase Adducts of the Anticancer Drug cis‐[PtCl2(NH3)(2‐picoline)] and Its trans Isomer
Authors: McGowan Geraldine , Parsons Simon , Sadler Peter J.
Published: May 2005

cis‐[PtCl2(NH3)(2‐picoline)] (AMD473) is a sterically‐hindered anticancer complex with a profile of chemical and biological activity that differs significantly from that of cisplatin. Adducts of AMD473 with neutral 9‐ethylguanine (9‐EtGH) and anionic (N1‐deprotonated) 9‐ethylguanine (9‐EtG) as perchlorate and nitrate salts, and also a nitrate salt of the trans isomer (AMD443), were prepared and their structures determined by X‐ray crystallography: cis‐[Pt(NH3)(2‐pic)(9‐EtGH)2](ClO4)2 (1)⋅2 H2O⋅Me2CO, cis‐[Pt(NH3)(2‐pic)(9‐EtGH)2](NO3)2 (2)⋅2 H2O, cis‐[Pt(NH3)(2‐pic)(9‐EtGH)(9‐EtG)]NO3 (3)⋅3.5 H2O, trans‐[Pt(NH3)(2‐pic)(9‐EtGH)(9‐EtG)]NO3 (4)⋅8 H2O. In all cases, platinum coordination is through N7 of neutral (1, 2) and anionic (3, 4) guanine. In each complex, the guanine bases are arranged in the head‐to‐tail conformation. In complex 1, there is an infinite array of six‐molecule cycles, based on both hydrogen bonding and π–π stacking of the 2‐picoline and guanine rings. Platinum(II) coordinated at N7 acidifies the N1 proton of neutral 9‐ethylguanine (pKa=9.57) to give pKa1=8.40 and pKa2=8.75 for complex 2, and pKa1=7.77 and pKa2=9.00 for complex 4. In complexes 3 and 4, three intermolecular hydrogen bonds are formed between neutral and deprotonated guanine ligands involving O6, N1 and N2 sites. Unusually, both of the platinated guanine bases of complexes 3 and 4 participate in this triple GG hydrogen bonding. This is the first report of X‐ray crystal structures of nucleobase adducts of the promising anticancer drug AMD473.
Frequency of SOX Group B (SOX1, 2, 3) and ZIC2 antibodies in Turkish patients with small cell lung carcinoma and their correlation with clinical parameters
Authors: Vural Burcak , Chen Lin‐Chi , Saip Pinar , Chen Yao‐Tseng , Ustuner Zeki , Gonen Mithat , Simpson Andrew J. G. , Old Lloyd J. , Ozbek Ugur , Gure Ali O.
Published: May 2005

BACKGROUND

Expression of neuroectodermal markers is a key feature of small cell lung carcinoma (SCLC). Although immune responses against a number of these proteins have been associated with paraneoplastic neuronal disease (PND), most patients with SCLC have anti‐neuroectodermal antibodies in the absence of PND. Whether these immune responses affect the clinical outcome in SCLC is critical in understanding the potential value of these proteins as cancer vaccine targets as well as in the pathogenesis of PND.

METHODS

The authors investigated the frequency of immunoglobulin G autoantibodies against Sry‐like high‐mobility group box (SOX)1, 2, 3 and Zinc‐finger gene of the cerebellum (ZIC)2 proteins in stored serum samples from 90 patients utilizing the λ‐phage plaque assay. Data obtained from patient records were utilized to measure clinical correlates of seroreactivity.

RESULTS

Antibodies to SOX1 were present in 28% of patients and another 28% had anti‐ZIC2 antibodies, classifying these as some of the most frequent antibody responses observed in SCLC. None had autoimmune paraneoplastic disease. Antibody titers were frequently as high as ≥ 1:106 and were stable for ≤ 6 months after diagnosis. Seroreactivity against either SOX1 or ZIC2 correlated with younger age, lower lactate dehydrogenase levels, and better response to initial therapy.

CONCLUSIONS

The frequent and stable presence of SOX Group B and/or ZIC2 antibodies in SCLC, but not in healthy individuals examined, indicates they are serological markers of SCLC. However, the correlation between known clinical parameters of less aggressive disease and seroreactivity suggests that these antibodies are indicators of better prognosis in SCLC and warrants further studies to clarify the nature of the underlying immune responses. Cancer 2005. © 2005 American Cancer Society.
Differential expression ofvasaRNA and protein during spermatogenesis and oogenesis in the gibel carp (Carassius auratus gibelio), a bisexually and gynogenetically reproducing vertebrate
Authors: Xu Hongyan , Gui Jianfang , Hong Yunhan
Published: May 2005

The RNA helicase Vasa is a germ cell marker in animals, and its homolog in vertebrates to date has been limited to bisexual reproduction. We cloned and characterizedCagVasa, a Vasa homolog from the gibel carp, a fish that reproduces bisexually or gynogenetically.CagVasa possesses 14 RGG repeats and eight conserved motifs of Vasa proteins. In bisexually reproducing gibel carp,vasais maternally supplied and its zygotic expression is restricted to gonads. By in situ hybridization on testicular sections,vasais low in spermatogonia, high in primary spermatocytes, reduced in secondary spermatocytes, but disappears in spermatids and sperm. In contrast,vasapersists throughout oogenesis, displaying low–high–low levels from oogonia over vitellogenic oocytes to maturing oocytes. A rabbit anti‐Vasa antibody (αVasa) was raised against the N‐terminalCagVasa for fluorescent immunohistochemistry. On testicular sections, Vasa is the highest in spermatogonia, reduced in spermatocytes, low in spermatids, and absent in sperm. In the ovary, Vasa is the highest in oogonia but persists throughout oogenesis. Subcellular localization ofvasaand its protein changes dynamically during oogenesis. The αVasa stains putative primordial germ cells in gibel carp fry. It detects gonadal germ cells also in several other teleosts. Therefore,Cagvasaencodes a Vasa ortholog that is differentially expressed in the testis and ovary. Interestingly, the αVasa in combination with a nuclear dye can differentiate critical stages of spermatogenesis and oogenesis in fish. The cross‐reactivity and the ability to stain stage‐specific germ cells make this antibody a useful tool to identify fish germ cell development and differentiation. Developmental Dynamics 233:872–882, 2005. © 2005 Wiley‐Liss, Inc.
Specific requirements of sonic hedgehog signaling during oligodendrocyte development
Authors: Oh Saeock , Huang Xi , Chiang Chin
Published: May 2005

Oligodendrocyte precursors (OLPs) in the developing spinal cord are generated from the same part of the ventral neuroepithelium as motor neurons, by inductive processes that include a temporal switch from neuronal to glial cell fate. Recent studies have implicated Shh as a key signal in the generation of both OLPs and ventral neurons. In this study, we used Shh−/−, Gli3−/−, and Shh−/−;Gli3−/− mutants to address the role of Shh signaling during oligodendrocyte development. We find that, in the absence of Gli3, Shh signaling is dispensable for the generation and maintenance of OLPs. However, Shh is required for OLPs to emerge at the appropriate developmental stages and for subsequent differentiation of OLPs into mature oligodendrocytes. The initial delay and reduction in OLP generation in Shh−/−;Gli3−/− mutants are accompanied by extended neurogenesis and persistent expression of Neurogenin 2 in the Olig2 progenitor domain, suggesting that Shh signaling influences the timing of neuron–glia fate switching. Thus, our studies suggest that Shh signaling plays multiple roles during development of oligodendrocytes. Developmental Dynamics 234:489–496, 2005. © 2005 Wiley‐Liss, Inc.
The Mechanism of Hydrolysis of Aryl Ether Derivatives of3‐Hydroxymethyltriazenes
Authors: Carvalho Emília , Francisco Ana Paula , Iley Jim , Rosa Eduarda
Published: May 2005

1‐Aryl‐3‐aryloxymethyl‐3‐methyltriazenes hydrolyse to the corresponding anilines and phenols by specific‐acid‐catalysed, general‐acid‐catalysed and pH‐independent mechanisms. All compounds studied exhibit specific‐ and general acid catalysis, though for 5a general acid catalysis was not observed below a pH of approximately 4, while for compounds 5e,f, such catalysis was absent above a pH of approximately 5. The pH‐independent pathway is observed only for those compounds, 5d–f, that contain good aryloxy nucleofugic groups. The specific‐acid‐catalysed pathway is supported by a solvent deuterium isotope effect (SDIE) of 0.64, consistent with a mechanism involving protonation of the substrate followed by rate‐determining unimolecular decomposition of the protonated species. The kH+ values gave rise to a Hammett ρ value of –0.93, reflecting the competing effect of the substituents on the protonation of the substrate and the cleavage of the aryl ether. Correlation of kH+ with the pKa of the phenol leaving group affords a βlg of 0.3. Decomposition of the protonated intermediate proceeds via a triazenyliminium ion that can be trapped by methanol. The general‐acid‐catalysed process exhibits an SDIE of 1.43 and Hammett ρ values of 0.49, 0.84 and 1.0 for reactions catalysed by chloroacetic, formic and acetic acids, respectively. Correlation of kA with the pKa of the acid gave Brønsted α values that diminish from 0.6 for O‐aryl systems that are poor nucleofuges (5a,b) to 0.2 for the best nucleofuge (5f), reflecting the different extents of proton transfer required to expel each phenol. Compounds containing powerful nucleofuges exhibit a pH‐independent reaction that has an SDIE of 1.1, a Hammett ρ value of 3.4 and a Brønsted βlg value of 1.4. These imply a mechanism involving displacement of the aryloxide leaving group to form a triazenyliminium ion intermediate that again was trapped as a methyl ether. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Mechanism of the Reaction of Lawesson’s Reagent with N‐Alkylhydroxamic Acids
Authors: Przychodzeń Witold
Published: May 2005

The mechanism of the reaction under discussion has been established by investigating the products of the reaction between 2,4‐bis(4‐methoxyphenyl)‐1,3,2,4‐dithiadiphosphetane 2,4‐disulfide (Lawesson’s reagent, LR) and N‐alkylhydroxamic acids HAs 1. The primary intermediate is an adduct, O‐dithiophosphonylated hydroxamic acid 19, which decomposes to yield metathiophosphonate (AnsPOS), a sulfur atom, and an amide. At the same time, owing to the co‐existence of 19 and metadithiophosphonate (AnsPSS) in equilibrium, the carbonyl group is thionated. It has also been established that monomeric AnsPOS formed in both reduction and thionation processes does not undergo oligomerisation to cyclic trimer 5 and linear oligomers, which is typical for amides reacting with LR. Since there is unreacted HA 1 in the reaction mixture, AnsPOS takes part in a controlled transformation to form a dimer, the corresponding pyrothiophosphonate 3, together with the intermediate O‐thiophosphonylated hydroxamic acid 2. A hydrolysed product of AnsPOS, namely (4‐methoxyphenyl)thiophosphonic acid 4, participates in the last reaction. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Efficient Routes to Acenaphthylene‐Fused Polycyclic Arenes/Heteroarenes and Heterocyclic Fluoranthene Analogues
Authors: Panda Kausik , Venkatesh Chelvam , Ila Hiriyakkanavar , Junjappa Hiriyakkanavar
Published: May 2005

The acenaphthenone‐derived α‐oxoketene dithioacetal 2 has been subjected to various [3 + 3] aromatic and heteroaromatic annulation and other heterocyclization reactions previously developed in our laboratory, providing short and efficient routes to a diverse range of known and unknown acenaphtho‐annulated linear and angular PAHs, heteroaromatics and five‐membered heterocycles in good yields. Thus, benzo‐ and naphthoannulation of 2 with various allyl and benzyl Grignard reagents afforded substituted fluoranthenes 4a–c and benzo[k]fluoranthene 8, respectively, in good yields. Similarly, the parent benzo[j]fluoranthene 15a and its substituted derivative 16b have been synthesized by base‐induced conjugate 1,4‐addition of arylacetonitriles to 2, followed by acid‐induced cyclization of the conjugate adducts 12a–b to give 13a–b and subsequent further transformations. The adducts obtained by 1,4‐addition of anions derived from acetophenone and acenaphthenone were subjected toheterocyclization in the presence of ammonium acetate to give 8‐arylacenaphtho[1,2‐b]pyridines 18a–b and bis(acenaphtho)‐annulated pyridine 20. Heterocyclization of 2 with bifunctional nucleophiles such as 2‐picolyllithium and guanidinium nitrate afforded the corresponding acenaphtho[1,2‐b]quinolizinium salt 23 and acenaphtho[1,2‐d]pyrimidine 24, respectively, in high yields. Finally, acenaphtho[1,2‐c]‐fused five‐membered heterocycles such as 7‐(methylthio)acenaphtho[1,2‐c]thiophene (25), 7‐(methylthio)acenaphtho[1,2‐c]furan (27) and 7‐(methylthio)acenaphtho[1,2‐c]pyrrole‐2‐carboxylic acid (30) were obtained in good yields by subjection of 2 to Simmons–Smith reaction conditions or by treatment with dimethylsulfonium methylide or glycinate dianion. Some of these newly synthesized PAHs or fused heterocycles were subjected to Raney Ni desulfurization to furnish sulfur‐free compounds. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Novel Highly Efficient P‐Chiral Ferrocenylimino Diamidophosphite Ligands for Pd‐Catalysed Asymmetric Allylation
Authors: Tsarev Vasily N. , Lyubimov Sergey E. , Bondarev Oleg G. , Korlyukov Alexander A. , Antipin Mikhail Yu. , Petrovskii Pavel V. , Davankov Vadim A. , Shiryaev Alexei A. , Benetsky Eduard B. , Vologzhanin Pavel A. , Gavrilov Konstantin N.
Published: May 2005

Novel P*‐chiral P,N‐bidentate ligands were synthesized by treatment of ferrocene‐based imino alcohols with chlorophosphites derived from (S)‐2‐anilinomethylpyrrolidine or (S)‐prolinol. Metal chelate complexes with the ligands – [Rh(CO)(PN)Cl] and [Pd(PN)(allyl)]+X– (X– = BF4–, Cl–, I–, CH12B11–) – were obtained and all new compounds were fully characterized by 1H, 13C, 31P NMR, IR, MS (EI, CI, FAB, ESI and plasma desorption techniques) and X‐ray analysis (imino alcohol 2d and complex 7). P*‐Chiral diamidophosphites gave up to 97 % ee in the Pd‐catalysed allylic substitution of 1,3‐diphenylallyl acetate with dimethyl malonate and para‐toluenesulfinate. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Synthesis of Enantiomerically Pure Dissymmetric 2,2'‐Disubstituted9,9'‐Spirobifluorenes
Authors: Thiemann Frank , Piehler Torsten , Haase Detlev , Saak Wolfgang , Lützen Arne
Published: May 2005

Racemic dissymmetric 2,2'‐dihydroxy‐9,9'‐spirobifluorene was prepared and resolved by clathrate formation with (R,R)‐(+)‐2,3‐dimethoxy‐N,N,N',N'‐tetracyclohexylsuccindiamide, giving rise to both enantiomers in very good yields. The absolute stereochemistry of the resolved material could be assigned by an X‐ray structure analysis of single crystals of the clathrate. Enantiomerically pure diols could be transformed into the corresponding ditriflates, which were then used as starting materials in different cross‐coupling procedures to provide a number of new enantiomerically pure spiro compounds bearing versatile functional groups suitable for further elaboration, as demonstrated by some examples. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Regioselective Synthesis of Functionalized Furans by Cyclization of 1,3‐Bis‐Silyl Enol Ethers with 1‐Chloro‐2,2‐dimethoxyethane
Authors: Bellur Esen , Görls Helmar , Langer Peter
Published: May 2005

Cyclization of 1,3‐bis‐silyl enol ethers with 1‐chloro‐2,2‐dimethoxyethane allowed an efficient, regio‐ and diastereoselective synthesis of a variety of 2‐alkylidene‐4‐methoxytetrahydrofurans. The TFA‐mediated elimination of methanol resulted in the formation of functionalized furans. Similarly, 2,3,3a,4,5,6‐hexahydro‐2,3‐benzofurans were prepared and transformed into 4,5,6,7‐tetrahydro‐2,3‐benzofurans by treatment with TFA. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Concise Synthesis of (4R,9Z)‐Octadec‐9‐en‐4‐olide, the Female Sex Pheromone of Janus integer
Authors: Mori Kenji
Published: May 2005

(4R,9Z)‐Octadec‐9‐en‐4‐olide, the female sex pheromone of the currant stem girdler (Janus integer), was synthesized in gram quantities by employing Sharpless asymmetric dihydroxylation (AD) and Jacobsen hydrolytic kinetic resolution (HKR). Crystalline (R)‐hexadec‐7‐yne‐1,2‐diol (87 % ee), obtained by AD and purified by recrystallization, was converted into (R)‐1,2‐epoxyhexadec‐7‐yne (87 % ee), which was further purified to 96 % ee by HKR. The epoxide was converted into the target lactone in 14 % overall yield based on hex‐5‐en‐1‐ol (11 steps). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Enzyme‐Catalysed Transformations of ent‐Kaurane Diterpenoids
Authors: Monsalve Leandro N. , Rosselli Sergio , Bruno Maurizio , Baldessari Alicia
Published: May 2005

Several acetyl derivatives of linearol, atractyligenin and atractylitriol were obtained through enzyme‐catalysed acetylation and deacetylation reactions. In most reactions lipases showed regio‐ and stereoselective behaviour, allowing a family of novel compounds to be prepared. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
New Highly Active and Selective Heterogeneous Catalytic System for the Synthesis of Unsymmetrical Organic Carbonates: A Green Protocol
Authors: Veldurthy Bhaskar , Clacens Jean‐Marc , Figueras François
Published: May 2005

A green, efficient, and selective synthesis of unsymmetrical organic carbonates is realised in the liquid phase by direct condensation of an alcohol and diethyl carbonate, in an eco‐compatible route, in the presence of a recyclable heterogeneous solid‐base CsF/α‐Al2O3 catalyst. The catalyst displayed unprecedented activity after activation at 393 K for 4 h and produced quantitative yields with a greater rate compared with solid bases reported so far. The present process is a potential alternative to replace soluble bases in commercial synthesis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Metal Complexation by Tripodal N‐Acyl(thio)urea and Picolin(thio)amide Compounds: Synthesis/Extraction and Potentiometric Studies
Authors: Reinoso‐García Marta M. , Dijkman Arjan , Verboom Willem , Reinhoudt David N. , Malinowska Elżbieta , Wojciechowska Dorota , Pietrzak Mariusz , Selucky Pavel
Published: May 2005

The synthesis and binding properties towards different cations of a series of tripodal ligands functionalized with N‐acyl(thio)urea and picolin(thio)amide moieties are described. For the extraction of Am3+ and Eu3+ the compounds are not efficient. However, N‐acylurea derivative 10 exhibit a significant selectivity for Am3+ over Eu3+. Upon addition of the synergistic hexabrominated bis(dicarbollide)cobalt anion (Br6‐COSAN) the distribution coefficients for Am3+ and Eu3+ increase up to 1000 for picolinamide derivative 11. Extraction studies with metal picrates (Pb2+, Cu2+, Ag+, Hg2+, Cd2+, Eu3+, Fe3+, K+, Na+, and Ca2+) or the incorporation in ion selective electrodes (ISEs), show that picolinamide derivative 11 is a very selective and strong ionophore for Hg2+ and that N‐acylthiourea 8 is a very good ionophore for Ag+. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Thermus thermophilus Glycosynthases for the Efficient Synthesis of Galactosyl and Glucosyl β‐(1→3)‐Glycosides
Authors: Drone Jullien , Feng Hui‐yong , Tellier Charles , Hoffmann Lionel , Tran Vinh , Rabiller Claude , Dion Michel
Published: May 2005

Inverting mutant glycosynthases were designed according to the Withers strategy, starting from wild‐type Thermus thermophilus retaining Tt‐β‐Gly glycosidase. Directed mutagenesis of catalytic nucleophile glutamate 338 by alanine, serine, and glycine afforded the E338A, E338S, and E338G mutant enzymes, respectively. As was to be expected, the mutants were unable to catalyze the hydrolysis of the transglycosidation products. In agreement with previous results, the E338S and E338G catalysts were much more efficient than E338A. Moreover, our results showed that these enzymes were inactive in the hydrolysis of the α‐D‐glycopyranosyl fluorides used as donors, and so suitable experimental conditions, under which the rate of spontaneous hydrolysis of the donor was considerably lower than that of enzymatic transglycosidation, provided galactosyl and glucosyl β‐(1→3)‐glycosides in yields of up to 90 %. The structure of native Tt‐β‐Gly available in the Protein Data Bank offers a good basis for interpretation of our results by means of molecular modeling. Thus, in the case of the E338S mutant, a lower energy of the system was obtained when the donor and the acceptor were in the right position to form the β‐(1→3)‐glycosidic bond. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Nucleophilic Carbenes and Pseudo‐Cross‐Conjugated Mesomeric Betaines of Indazole Starting from Analogues of the Alkaloid‐Betaine Nigellicine
Authors: Schmidt Andreas , Merkel Lars , Eisfeld Wolfgang
Published: May 2005

The alkaloid Nigellicine possesses the indazolium‐3‐carboxylate ring system as electronically relevant partial structure which represents a member of the class of pseudo‐cross‐conjugated mesomeric betaines. Indazolium‐3‐carboxylate, prepared starting from indazole‐3‐carboxylic acid by an esterification–methylation–saponification sequence, can be converted into the isoconjugated phenyl‐ and 4‐(nitrophenyl)amidates and the thiocarboxylate as additional examples of pseudo‐cross‐conjugated systems. In accordance with results of ab initio calculations decarboxylation of indazolium‐3‐carboxylate with formation of the nucleophilic carbene indazol‐3‐ylidene begins at approximately 40 °C as evidenced by temperature‐dependent NMR spectroscopy. The carbene can be trapped with protons as indazolium salts, and carbon dioxide which reconstitutes the pseudo‐cross‐conjugated mesomeric betaine. According to the calculations, the carbene adopts a singlet ground state. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Catalytic Activation of Silylated Nucleophiles Using tBu‐P4 as a Base
Authors: Ueno Masahiro , Hori Chieko , Suzawa Koichi , Ebisawa Masashi , Kondo Yoshinori
Published: May 2005

Trialkylsilyl groups play an important role as effective protecting groups in organic synthesis. Various O, N, and C nucleophilic sites can be protected by trialkylsilyl groups to control the selectivity of reactions. The nucleophilic attack of a fluoride anion on a silyl group is recognized as one of the most useful methods for desilylation. The activation of the nucleophile–silicon bond is important not only for desilylation but also for the generation of a reactive nucleophilic anion to achieve a new bond formation. The phosphazene bases developed by Schwesinger are known to be strong non‐metallic organic bases. Among them, the tBu‐P4 base has been used for various selective deprotonative transformations, although the ability of tBu‐P4 base to activate silylated nucleophiles has not yet been shown. A novel catalytic activation of various O, N, and C nucleophile–silicon bonds using tBu‐P4 base was investigated to perform nucleophilic reactions with various electrophiles. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
A Metathesis Approach to Aromatic Heterocycles
Authors: Donohoe Timothy J. , Orr Allan J. , Gosby Katherine , Bingham Matilda
Published: May 2005

The ring closing metathesis (RCM) reaction can be used to prepare substituted furans and pyrroles. By utilising a Pd‐catalysed coupling reaction with methoxyallene, allylic alcohols and sulfonamides can be converted into substrates that are ideal precursors to ring closing metathesis. After the RCM reaction is complete, the addition of acid promotes an elimination of methanol to form the fully aromatised system. A range of different substitution patterns and functional groups are compatible with this sequence. Double allene coupling, RCM and elimination reactions are also possible and allow the formation of biaryl systems. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Cover Picture: Thermus thermophilus Glycosynthases for the Efficient Synthesis of Galactosyl and Glucosyl β‐(1→3)‐Glycosides (Eur. J. Org. Chem. 10/2005)
Authors: Drone Jullien , Feng Hui‐yong , Tellier Charles , Hoffmann Lionel , Tran Vinh , Rabiller Claude , Dion Michel
Published: May 2005

The cover picture shows the molecular modeling of the active site of a “glycosynthase” mutant obtained by directed mutagenesis (E338S) of the native thermostable Tt‐β‐Glyglycosidase from Thermus thermophilus. The relative orientations of the donor (α‐D‐glucopyranosyl fluoride) and of the acceptor (phenyl β‐D‐glucopyranoside), which corresponded to an energy minimum, were in agreement with the β‐(1→3) regioselectivity exhibited by this E338S mutant enzyme. The stabilization of the initial ligands in this state, particularly due to stacking between the phenyl aglycon group of the acceptor and W312, gives an explanation for the very good transglycosydation yields (95%) obtained by using phenyl β‐D‐glucopyranoside. Details are discussed in the article by M. Dion et al. on p. 1977 ff.
Light‐dependent mutagenesis by benzo[a]pyrene is mediated via oxidative DNA damage
Authors: Kim Su‐Ryang , Kokubo Kiyoko , Matsui Keiko , Yamada Noriyo , Kanke Yusuke , Fukuoka Masamichi , Yamada Masami , Nohmi Takehiko
Published: May 2005

Benzo[a]pyrene (B[a]P) is an environmental carcinogenic polycyclic aromatic hydrocarbon (PAH). Mammalian enzymes such as cytochrome P‐450s and epoxide hydrase convert B[a]P to reactive metabolites that can covalently bind to DNA. However, some carcinogenic compounds that normally require metabolic activation can also be directly photoactivated to mutagens. To examine whether B[a]P is directly mutagenic in the presence of light, we exposed Salmonella typhimurium strains with different DNA repair capacities to B[a]P and white fluorescent light at wavelengths of 370–750 nm. B[a]P plus light significantly enhanced the number of His+ revertants. Mutagenesis was completely light‐dependent and required no exogenous metabolic activation. The order of mutability of strains with different DNA repair capacities was strain YG3001 (uvrB, mutMST) ≫ strain TA1535 (uvrB) > strain YG3002 (mutMST) > strain TA1975. The uvrB gene product is involved in the excision repair of bulky DNA adducts, and the mutMST gene encodes 8‐oxoguanine (8‐oxoG) DNA glycosylase, which removes 8‐oxoG from DNA. Introduction of a plasmid carrying the mOgg1 gene that is the mouse counterpart of mutMST substantially reduced the light‐mediated mutagenicity of B[a]P in strain YG3001. B[a]P plus light induced predominantly G:C → T:A and G:C → C:G transversions. We propose that B[a]P can directly induce bulky DNA adducts if light is present, and that the DNA adducts induce oxidative DNA damage, such as 8‐oxoG, when exposed to light. These findings have implications for the photocarcinogenicity of PAHs. Environ. Mol. Mutagen., 2005. © 2005 Wiley‐Liss, Inc.
Localization of a putative low‐penetrance ependymoma susceptibility locus to 22q11 using a chromosome 22 tiling‐path genomic microarray
Authors: Ammerlaan Anneke C. J. , de Bustos Cecilia , Ararou Abdelhay , Buckley Patrick G. , Mantripragada Kiran K. , Verstegen Marco J. , Hulsebos Theo J. M. , Dumanski Jan P.
Published: May 2005

Ependymomas frequently display allelic loss of chromosome 22 in the absence of mutations in the known tumor‐suppressor genes on chromosome 22, suggesting the role of an alternative predisposing gene or genes from this chromosome. In an effort to localize these genes, 37 ependymomas derived from 33 patients were analyzed for the presence of copy number changes by use of a high‐resolution chromosome 22 genomic microarray. Eighteen ependymomas (49%) displayed an array‐CGH profile consistent with monosomy of chromosome 22. However, in 10 of these tumors, the fluorescence ratios for 22q clones scored as deleted were different from those at the single gene copy level. This suggests either analysis of mixed populations of tumor and normal stromal cells or analysis of mixed tumor cell populations with different genetic profiles. Four ependymomas derived from two patients showed overlapping interstitial deletions of 2.2 Mb and ∼510 kb. Further analyses revealed that these deletions were present in the constitutional DNA of these two patients as well as in some of their unaffected relatives. Detailed microsatellite analysis of these families refined the commonly deleted segment to a region of 320 kb between markers RH13801 and D22S419. Our results provide additional evidence for the involvement of genes on chromosome 22 in the development of ependymoma and suggest the presence of a low‐penetrance ependymoma susceptibility locus at 22q11. © 2005 Wiley‐Liss, Inc.
Identification of recurrent chromosomal aberrations in germ cell tumors of neonates and infants using genomewide array‐based comparative genomic hybridization
Authors: Veltman Imke , Veltman Joris , Janssen Irene , Hulsbergen‐van de Kaa Christina , Oosterhuis Wolter , Schneider Dominik , Stoop Hans , Gillis Ad , Zahn Susanne , Looijenga Leendert , Göbel Ulrich , van Kessel Ad Geurts
Published: May 2005

Human germ cell tumors (GCTs) of neonates and infants comprise a heterogeneous group of neoplasms, including teratomas and yolk sac tumors with distinct clinical and epidemiologic features. As yet, little is known about the cytogenetic constitution of these tumors. We applied the recently developed genomewide array‐based comparative genomic hybridization (array CGH) technology to 24 GCTs derived from patients under the age of 5 years. In addition, we included seven tumors derived from children and adolescents older than 5 years. In the series from those under the age of 5 years, most teratomas displayed normal profiles, except for some minor recurrent aberrations. In contrast, the yolk sac tumors displayed recurrent losses of 1p35–pter and gains of 3p21–pter and of 20q13. In the GCTs of patients older than 5 years, the main recurrent anomalies included gains of 12p and of whole chromosomes 7 and 8. In addition, gains of the 1q32–qter region and losses of the 6q24–qter and 18q21–qter regions were frequent in GCTs of varied histology, independent of age. We concluded that array CGH is a highly suitable method for identifying recurrent chromosomal anomalies in GCTs of neonates and infants. The recurrent anomalies observed point to chromosomal regions that may harbor novel diagnostic/prognostic identifiers and genes relevant to the development of these neoplasms. © 2005 Wiley‐Liss, Inc.
Prevalence estimates of recurrent balanced cytogenetic aberrations and gene fusions in unselected patients with neoplastic disorders
Authors: Mitelman Felix , Mertens Fredrik , Johansson Bertil
Published: May 2005

Chromosome abnormalities have been reported in more than 46,000 benign and malignant neoplastic disorders, leading to the identification of numerous recurrent abnormalities. A substantial number of recurrent balanced aberrations (RBAs), in particular, reciprocal translocations, occur with remarkable specificity in association with clinical and tumor characteristics. This information has become increasingly important both in basic cancer research, as a means to identify pathogenetically important genes, and clinically, as a diagnostic and prognostic instrument. Knowledge of the frequencies of such aberrations thus is of theoretical as well as practical value. However, it is unknown to what extent the data available in the literature reflect reality. A large proportion of the published cases, at least 40%, are biased, in the sense that they were reported because of a specific or unusual karyotypic feature. We have systematically ascertained all RBAs and present data on the frequencies of these abnormalities and their molecular genetic consequences among unselected patients, that is, those studied as part of investigations of consecutive series of individuals with a particular neoplastic disorder. The salient features of the present study are: (1) published data clearly overestimate the prevalence of individual RBAs in most tumor types as well as the proportion of patients having such aberrations. In fact, several well‐known published RBAs are not recurrent or have not even been seen among unselected patients, and in no tumor entity, except for chronic myeloid leukemia, does the frequency of unselected cytogenetically abnormal neoplasms with RBAs exceed 35%; (2) the proportions of unselected cases characterized by RBAs among those tumor entities in which at least one RBA has been identified vary considerably both within and among hematologic malignancies, malignant lymphomas, and solid tumors; and (3) the molecular consequences of a substantial proportion, ranging from 19% in hematologic malignancies to 65% in epithelial tumors, of the most common RBAs in unselected patients remain to be clarified. © 2005 Wiley‐Liss, Inc.
New stool tests for colorectal cancer screening: A systematic review focusing on performance characteristics and practicalness
Authors: Haug Ulrike , Brenner Hermann
Published: May 2005

New stool tests may be promising tools for future colorectal cancer (CRC) screening. The aim of this review was to summarize current evidence of performance characteristics and practicalness in a population‐based screening setting of recently developed stool tests. The MEDLINE database was searched for relevant articles published until July 2004. Studies were included if they comprised more than 10 cases and more than 10 controls. Details on study population, performance characteristics and stool collection procedure were taken into account. Overall, 29 studies, mostly retrospective, were included, investigating 17 different stool markers or marker combinations. Underlying study populations were very heterogeneous and mostly very small. Half of the studies reported sensitivity for adenomas in addition to sensitivity for CRC, and fewer than half reported sensitivity by tumor stage or location. Performance characteristics of stool tests varied to a large extent. For most DNA‐based markers, specificity was about 95% or higher, but sensitivity was mostly low even for invasive CRC. More studies with larger sample sizes were done for protein‐based markers, which typically had lower specificity. In most studies, stool samples were frozen within a rather short time period after defecation. While promising performance characteristics have been reported for some tests, more pervasive evidence from larger, prospectively designed studies, which also consider aspects of practicalness, e.g., the possibility of mailing the samples, is needed. © 2005 Wiley‐Liss, Inc.
Thyroid cancer and multiple primary tumors in the SEER cancer registries1
Authors: Ronckers Cécile M. , McCarron Peter , Ron Elaine
Published: May 2005

Thyroid cancer incidence rates have increased steadily in the United States and elsewhere. Radiation exposure at a young age is a strong risk factor, but otherwise the etiology is unclear. To explore etiologic clues, we studied the risk of thyroid cancer after an earlier primary cancer, as well as the risk of developing multiple primaries after an earlier thyroid cancer in the U.S. Surveillance, Epidemiology and End‐Results (SEER) cancer registries program (1973–2000). In 2,036,597 patients diagnosed with any invasive cancer who survived for a minimum of 2 months, we observed a 42% increased risk compared to the general population for second thyroid cancer based on 1,366 cases (95% confidence interval (CI) = 35–50%; excess absolute risk (EAR) = 0.38/10,000 person‐years (PY)). Elevated risks were observed after most cancer sites studied. The most pronounced excess (observed/expected (O/E) = 2.86) was seen for second thyroid cancers detected in the year after diagnosis of the first cancer. Among 29,456 2‐month thyroid cancer survivors, 2,214 second cancers occurred (O/E = 1.11, 95% CI = 1.06–1.15; EAR = 7.64/10,000 PY). Again, the highest risk was seen in the first year (O/E = 1.26). Patients <40 years of age at diagnosis of thyroid cancer had a 39% increased risk of a second cancer, whereas for older patients the risk was elevated 6%. We observed consistently increased risks for cancers of the breast, prostate, and kidney, and a likely radiation treatment‐related excess of leukemia. Based on small numbers of cases, cancers of the salivary glands, trachea, scrotum, adrenal glands, and brain and central nervous system (CNS) also occurred in excess. A decreased risk was observed for smoking‐related malignancies. Thyroid cancer is associated with primary cancers of many different organs. Although enhanced medical surveillance likely plays a role, 2‐way, positive associations between thyroid cancer and cancers of the breast, prostate, kidney, salivary glands, brain and CNS, scrotum, and leukemia suggest etiologic similarities and possible treatment effects. © 2005 Wiley‐Liss, Inc.
Black tea induces tumor cell apoptosis by Bax translocation, loss in mitochondrial transmembrane potential, cytochrome c release and caspase activation
Authors: Bhattacharyya Arindam , Lahiry Lakshmishri , Mandal Debaprasad , Sa Gaurisankar , Das Tanya
Published: May 2005

Recently the anti‐cancer role of black tea has gained immense importance. Nevertheless, the signaling pathways underlying black tea‐induced tumor cell death are still unknown. Previously we reported that black tea induces Ehrlich's ascites carcinoma (EAC) cell apoptosis by changing the balance between pro‐and anti‐apoptotic proteins. It is now well accepted that many cell death pathways converge at the mitochondria to decrease mitochondrial transmembrane potential (MTP) thereby releasing apoptogenic proteins and resulting in the activation of effecter caspases responsible for the biochemical and morphological alterations associated with apoptosis. The role of pro‐apoptotic protein, Bax, in initiating mitochondrial death cascade has also been established. Here we demonstrate that in culture black tea extract induces EAC apoptosis in a dose‐dependent manner – with IC50 at 100 μg/ml. At this dose, intracellular Bax level increases in EAC followed by its translocation from cytosol to mitochondria resulting in loss in MTP. A search for the downstream pathway further reveals that black tea induces mitochondrial cytochrome c release and activates caspases 9 and 3 by 2 pathways, a) independent of and b) dependent on MTP loss. Interestingly, Black tea‐induced death signal might probably be amplified through mitochondrial membrane depolarization via a feedback activation loop from caspase 3. All these findings indicate that black tea initiates mitochondrial death cascade in EAC cells and thereby results in EAC apoptosis. © 2005 Wiley‐Liss, Inc.
4‐Aminobiphenyl induces liver DNA adducts in both neonatal and adult mice but induces liver mutations only in neonatal mice
Authors: Chen Tao , Mittelstaedt Roberta A. , Beland Frederick A. , Heflich Robert H. , Moore Martha M. , Parsons Barbara L.
Published: May 2005

The mechanisms underlying the susceptibility of neonatal mice to genotoxic carcinogens were investigated by analyzing the DNA adducts and mutations induced in the livers of neonatal and adult Big Blue transgenic mice by 4‐aminobiphenyl (4‐ABP), a potent human and rodent carcinogen. Neonatal and adult mice were treated with a regimen of 4‐ABP known to induce tumors in neonatal mice. Animals were sacrificed 1 day after the last treatment for DNA adduct analysis and 8 weeks after the last treatment for analysis of lacI and cII mutant frequency (MF). N‐(Deoxyguanosin‐8‐yl)‐4‐ABP was the major DNA adduct identified in the livers of the 4‐ABP‐treated mice and levels of this adduct were significantly higher in treated animals than in the controls for both the neonates and adults. Adduct levels for adult females (44.0 ± 4.8 adducts/106 nucleotides) were higher than in neonatal females (25.9 ± 2.2 adducts/106 nucleotides), while adduct levels in adult males (13.5 ± 2.0 adducts/106 nucleotides) were lower than in neonatal males (33.8 ± 4.1 adducts/106 nucleotides). 4‐ABP treatment significantly increased the liver cII MFs in both sexes of neonatal mice but not in adult mice. Sequence analysis of cII mutant DNA revealed that 4‐ABP induced a unique spectrum of mutations in neonatal mice, characterized by a high frequency of G:C→T:A transversion, while the mutation spectrum in 4‐ABP‐treated adults was similar to that of control mice. Our results indicate that DNA adduct formation by 4‐ABP depends as much on sex as it does on age, whereas the conversion of DNA adducts into mutations differed with animal age. These observations suggest that neonates are more sensitive than adults to genotoxic carcinogens because the relatively high levels of cell division in the developing animal facilitate the conversion of DNA damage into mutation. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat/index.html © 2005 Wiley‐Liss, Inc.