Copper(I) promoted C---C bond forming reactions: direct activation of allyl alcohols

Allylic alcohols, acetates, carbonates and chlorides can be activated by copper(I) salts towards nucleophilic substitution by carbon nucleophiles under relatively mild conditions.

Conformations of three heterocyclicperhydropyrrolobenzofurans and polymeric assembly via co-operative inter-molecular C-H center dot center dot center dot O hydrogen bonds

In 1-cyclo-hexyl-6,6,8a-trimethyl-3a,6,7,8a-tetra-hydro-1H-1-benzofuro[2,3-b]pyrrole-2,4(3H,5H)-dione, C19H27NO3, (I), and the isomorphous compounds 6,6,8a-trimethyl-1-phenyl-3a,6,7,8a-tetra-hydro-1H-1-benzofuro[2,3-b]pyrrole-2,4(3H,5H)-dione, C19H21NO3, (II), and 6,6,8a-trimethyl-1-(3-pyridyl)-3a,6,7,8a-tetra-hydro-1H-1-benzofuro[2,3-b]pyrrole-2,4(3H,5H)-dione, C18H20N2O3, (III), the tetra-hydro-benzo-dihydro-furo-pyrrolidine ring systems are folded at the cis junction of the five-membered rings, giving rise to a non-planar shape of the tricyclic cores. The dihydro-furan and pyrrolidine rings in (I) are puckered and adopt an envelope conformation. The cyclo-hexene rings adopt a half-chair conformation in all the mol-ecules, while the substituent N-cyclo-hexyl ring in (I) assumes a chair form. Short intra-molecular C-HcO contacts form S(5) and S(6) motifs. The isomorphous compounds (II) and (III) are effectively isostructural, and aggregate into chains via inter-molecular C-HcO hydrogen bonds.

Crystal structure and conformation study of N-methyl-t-3-methyl-r-2, c-6-diphenylpiperidin-4-one thiosemicarbazone

Thiosemicarbazones are having the ability to bind with metal and inhibit the enzyme ribonucleoside diphosphate reductase(RDR),an enzyme which is involved in the synthesis of DNA precursors in the mammalian cells.The title compound N-methyl-t-3-methyl-r-2, c-6-diphenylpiperidin-4-one thiosemicarbazone (NMMDPT), CCDC 218052, was prepared using Mannich reaction and characterized by X-ray diffraction methods.The crystal data are:C20H24N4S; M.W= 352.49, triclinic,space group P (1) over bar, a = 8.467(2)angstrom, b = 10.228(2)angstrom, c = 12.249(2)angstrom; lpha=92.595(3)degrees, beta=104.173(3)degrees, gamma=13.628(3)degrees; V=930.0(3)angstrom(3), Z=2, D-cal=1.259Mgm(-3),mu=0.184mm(-1),lambda (MoKalpha)=0.71073 angstrom, final R1 and wR2 are 0.0470 and 0.1052, respectively. The piperidine rings adopt chair conformation. The planar phenyl rings are oriented equatorially at 2,6-positions of the piperidine ring. The molecular packing can be viewed as dimers held together by two N-H...S types of intermolecular hydrogen bonds. Weak C-H...pi interactions also support the stability of the molecules in the crystal in addition to van der Waals forces. (c) 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Conformations of three heterocyclic perhydropyrrolobenzofurans and polymeric assembly via co-operative inter-molecular C-H center dot center dot center dot O hydrogen bonds

In 1-cyclo-hexyl-6,6,8a-trimethyl-3a,6,7,8a-tetra-hydro-1H-1-benzofuro2, 3-b]pyrrole-2,4(3H,5H)-dione, C19H27NO3, (I), and the isomorphous compounds 6,6,8a-trimethyl-1-phenyl-3a,6,7,8a-tetra-hydro-1H-1-benzofuro2,3-b]p yrrole-2,4(3H,5H)-dione, C19H21NO3, (II), and 6,6,8a-trimethyl-1-(3-pyridyl)-3a,6,7,8a-tetra-hydro-1H-1-benzofuro2, 3-b]pyrrole-2,4(3H,5H)-dione, C18H20N2O3, (III), the tetra-hydro-benzo-dihydro-furo-pyrrolidine ring systems are folded at the cis junction of the five-membered rings, giving rise to a non-planar shape of the tricyclic cores. The dihydro-furan and pyrrolidine rings in (I) are puckered and adopt an envelope conformation. The cyclo-hexene rings adopt a half-chair conformation in all the mol-ecules, while the substituent N-cyclo-hexyl ring in (I) assumes a chair form. Short intra-molecular C-HcO contacts form S(5) and S(6) motifs. The isomorphous compounds (II) and (III) are effectively isostructural, and aggregate into chains via inter-molecular C-HcO hydrogen bonds.

Measurement of the ttbar production cross section with an in situ calibration of b-jet identification efficiency

A measurement of the top-quark pair-production cross section in ppbar collisions at sqrt{s}=1.96 TeV using data corresponding to an integrated luminosity of 1.12/fb collected with the Collider Detector at Fermilab is presented. Decays of top-quark pairs into the final states e nu + jets and mu nu + jets are selected, and the cross section and the b-jet identification efficiency are determined using a new measurement technique which requires that the measured cross sections with exactly one and multiple identified b-quarks from the top-quark decays agree. Assuming a top-quark mass of 175 GeV/c^2, a cross section of 8.5+/-0.6(stat.)+/-0.7(syst.) pb is measured.

Total syntheses of the fungal metabolites (+/-)-acremines A, B and I

A concise and diversity-oriented approach, incorporating elements of regio- and stereocontrol, to the recently isolated bioactive polyoxygenated cyclohexanoid natural products acremines A. B and I. from commercially accessible building blocks, is outlined. (c) 2010 Elsevier Ltd. All rights reserved.

Synthetic studies toward the PPAP natural products, prolifenones A and B and hyperforin: an Effenberger cyclization approach

A synthetic approach toward the geranylated PPAP natural products, prolifenones A and B. employing Effenberger cyclization as the key step, is delineated. The efficacy of this approach is further expanded through access to an advanced precursor of hyperforin. (C) 2010 Elsevier Ltd. All rights reserved.

Peptide models for b-turns.A circular dichroism study

The circular dichroism spectra of four 0-turn model peptides, Z-Aib-Pro-Aib-Pro- OMe (l), Piv-Pro-Aib-NHMe (2), Piv-Pro-D-Ala-NHMe (3) and Piv-Pro-Val-NHMe (4) have been examined under a wide range of solvent conditions, using methanol, hexafluoroisopropanol and cyclohexane. Type I and Type I1 0-turns have been observed for peptides 1 and 2 respectively, in the solid state, while the Pro-D-Ala sequence adopts a Type I1 Sturn in a related peptide crystal structure. A class C spectrum is observed for 1 in various solvents, suggesting a variant of a Type I(II1) structure. The Type I1 f3-turn is characterized by a CD spectrum having two positive CD bands at - 230 nm and - 202 nm, a feature observed in Piv-Pro- D-Ala-NHMe in cyclohexane and methanol and for Piv-Pro-Aib-NHMe in methanol. Peptide 2 exhibits solvent dependent CD spectra, which may be rationalized by considering Type 11, I11 and V reverse turn structures. Piv-Pro- Val-NHMe adopts nonaturn structures in polar solvents, but exhibits a class B spectrum in cyclohexane suggesting a population of Type I &turns.

Differences in the climatic adaptation of silver birch (Betula pendula) and downy birch (B. pubescens) in Finland based on male flowering phenology.

Male flowering was studied at the canopy level in 10 silver birch (Betula pendula Roth) stands from 8 localities and in 14 downy birch (B. pubescens Ehrh.) stands from 10 localities in Finland from 1963 to 1973. Distributions of cumulative pollen catches were compared to the normal Gaussian distribution. The basis for the timing of flowering was the 50 per cent point of the anthesis-fitted normal distribution. To eliminate effects of background pollen, only the central, normally distributed part of the cumulative distribution was used. Development up to the median point of the distribution was measured and tested in calendar days, in degree days (> 5 °C) and in period units. The count of each parameter began on and included March 19. Male flowering in silver birch occurred from late April to late June depending on latitude, and flowering in downy birch took place from early May to early July. The heat sums needed for male flowering varied in downy birch stands latitudinally but there was practically no latitudinal variation in heat sums needed for silver birch flowering. The amount of male flowering in stands of both birch species were found to have a large annual variation but without any clear periodicity. The between years pollen catch variation in stands of either birch species did not show any significant latitudinal correlation in contrast to Norway spruce stands. The period unit heat sum gave the most accurate forecast of the timing of flowering for 60 per cent of the silver birch stands and for 78.6 per cent of the for downy birch stands. Calendar days, however, gave the best forecast for silver birch in 25 per cent of the cases, while degree days gave the best forecast for downy birch in 21.4 per cent of the cases. Silver birch seems to have a local inclination for a more fixed flowering date compared to downy birch, which could mean a considerable photoperiodic influence on flowering time of silver birch. Silver birch and downy birch had different geographical correlations. Frequent hybridization of birch species occurs more often in northern Finland in than in more southern latitudes. The different timing in flowering caused increasing scatter in flowering times in the north, especially in the case of downy birch. The chance of simultaneous flowering of silver birch and downy birch so increased northwards due to a more variable climate and also higher altitudinal variations. Compared with conifers, the reproduction cycles of both birch species were found to be well protected from damage by frost.

b-Turn conformations in crystal structures of model peptides containing a,a-di-n-propylglycine (Dpg) and a,a-di-n-butyl-glycine (Dbg).

The crystal state conformations of three peptides containing the a,a-dialkylated residues, a,adi n-propylglycine (Dpg) and a,@-di-n-butylglycine (Dbg), have been established by x-ray diffraction. Boc-Ala-Dpg-Ala-OMe ( I ) and Boc-Ala-Dbg-Ala-OMe (III) adopt distorted type II @-turn conformations with Ala ( I ) and Dpg/Dbg (2) as the corner residues. In both peptides the conformational angles at the Dxg residue (I: 4 = 66.23 J/ = 19.3'; III: 4 = 66S0, J. = 21 .la)deviate appreciablyfrom ideal values for the i + 2 residue in a type II @-turn. In both peptides the observed(N. 0) distances between the Boc CO andAla(3) NHgroups are far too long (I:3.44 k; III: 3.63 k) for an intramolecular 4 + 1 hydrogen bond. Boc-Ala-Dpg-Ala-NHMe (II)crystallizes with two independent molecules in the asymmetric unit. Both molecules IIA and IIB adopt consecutive @-turn (type III-III in IIA and type III-I in IIB) or incipient 3,,,-helical structures, stabilized by two intramolecular 4 --t I hydrogen bonds. In all four molecules the bond angle N-C"-C' ( T ) at the Dxg residues are 2 1109 The observation of conformational angles in the helical region of 4,J/ space at these residues is consistent with theoretical predictions

HDL subspecies : association with low HDL-C, obesity, and metabolic syndrome

AIMS An independent, powerful coronary heart disease (CHD) predictor is a low level of high-density lipoprotein cholesterol (HDL-C). Discoidal preβ-HDL particles and large HDL2 particles are the primary cholesterol acceptors in reverse cholesterol transport, a key anti-atherogenic HDL mechanism. The quality of HDL subspecies may provide better markers of HDL functionality than does HDL-C alone. We aimed I) to study whether alterations in the HDL subspecies profile exist in low-HDL-C subjects II) to explore the relationship of any changes in HDL subspecies profile in relation to atherosclerosis and metabolic syndrome; III) to elucidate the impact of genetics and acquired obesity on HDL subspecies distribution. SUBJECTS The study consisted of 3 cohorts: A) Finnish families with low HDL-C and premature CHD (Study I: 67 subjects with familial low HDL-C and 64 controls; Study II: 83 subjects with familial low HDL-C, 65 family members with normal HDL-C, and 133 controls); B) a cohort of 113 low- and 133 high-HDL-C subjects from the Health 2000 Health Examination Survey carried out in Finland (Study III); and C) a Finnish cohort of healthy young adult twins (52 monozygotic and 89 dizygotic pairs) (Study IV). RESULTS AND CONCLUSIONS The subjects with familial low HDL-C had a lower preβ-HDL concentration than did controls, and the low-HDL-C subjects displayed a dramatic reduction (50-70%) in the proportion of large HDL2b particles. The subjects with familial low HDL-C had increased carotid atherosclerosis measured as intima-media-thickness (IMT), and HDL2b particles correlated negatively with IMT. The reduction in both key cholesterol acceptors, preβ-HDL and HDL2 particles, supports the concept of impaired reverse cholesterol transport contributing to the higher CHD risk in low-HDL-C subjects. The family members with normal HDL-C and the young adult twins with acquired obesity showed a reduction in large HDL2 particles and an increase in small HDL3 particles, which may be the first changes leading to the lowering of HDL-C. The low-HDL-C subjects had a higher serum apolipoprotein E (apoE) concentration, which correlated positively with the metabolic syndrome components (waist circumference, TG, and glucose), highlighting the need for a better understanding of apoE metabolism in human atherosclerosis. In the twin study, the increase in small HDL3b particles was associated with obesity independent of genetic effects. The heritability estimate, of 73% for HDL-C and 46 to 63% for HDL subspecies, however, demonstrated a strong genetic influence. These results suggest that the relationship between obesity and lipoproteins depends on different elements in each subject. Finally, instead of merely elevating HDL-C, large HDL2 particles and discoidal preβ-HDL particles may provide beneficial targets for HDL-targeted therapy.

Visualization of enantiomers and determination of homo- and hetero-nuclear residual dipolar and scalar couplings: The natural abundant C-13 edited J/D-resolved NMR techniques

The simple two dimensional C-13-satellite J/D-resolved experiments have been proposed for the visualization of enantiomers, extraction of homo- and hetero-nuclear residual dipolar couplings and also H-1 chemical shift differences between the enantiomers in the anisotropic medium. The significant advantages of the techniques are in the determination of scalar couplings of bigger organic molecules. The scalar couplings specific to a second abundant spin such as F-19 can be selectively extracted from the severely overlapped spectrum. The methodologies are demonstrated on a chiral molecule aligned in the chiral liquid crystal medium and two different organic molecules in the isotropic solutions. (C) 2010 Elsevier B.V. All rights reserved.

Fatigue in Ti-6Al-4V-B alloys

The addition of small amounts of B to Ti-6Al-4V alloy reduces the as-cast grain size by an order of magnitude and introduces TiB phase into the microstructure. The effects of these microstructural modifications on both the high cycle fatigue and cyclic stress-strain response were investigated. Experimental results show that B addition markedly enhances the fatigue strength of the alloy; however, the influence of prior-beta grain size was found to be only marginal. The presence of TiB particles in the matrix appears to be beneficial with the addition of 0.55 wt.% B to Ti-6Al-4V enhancing the fatigue strength by more than 50%. Strain-controlled fatigue experiments reveal softening in the cyclic stress-strain response, which increases with the B content in the alloy. Transmission electron microscopy of the fatigued specimens indicates that generation of dislocations during cyclic loading and creation of twins due to strain incompatibility between the matrix and the TiB phase are possible reasons for the observed softening. (c) 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Basic and translational studies on species B adenoviruses

Human adenoviruses (Ads) have been classified into six species (A to F) currently containing 55 serotypes. For almost 2 decades vectors derived from group C serotype Ad5 have been extensively used for gene transfer studies. These Ad5 based vectors are able to efficiently infect many mammalian cell types (including both mitotic and post-mitotic cells) through interaction with a primary attachment receptor, the coxsackie and adenovirus receptor (CAR). Despite the many advantages of Ad5 based vectors a number of limitations have affected their therapeutic application to many diseases. Although they can transduce many tissue types, Ad5 based vectors are unable to efficiently transduce several potential disease target cell types, including hematopoietic stem cells and malignant tumor cells. Therefore, newer vectors have been developed based on Ad serotypes other than Ad5. This thesis focuses on species B Ads. Species B Ads are comprised of three groups based on their receptor usage. Group 1 of species B Ads (Ad16, 21, 35, 50) nearly exclusively utilize CD46 as a receptor; Group 2 (Ad3, Ad7, 14) share a common, unidentified receptor/s, which is not CD46 and which was tentatively named receptor X; Group 3 (Ad11) preferentially interacts with CD46, but also utilizes receptor X if CD46 is blocked. Species B group Ads are important human pathogens. Species B group 2 serotypes are isolated from patients with respiratory tract infections, whereas the Group 1 viruses are described as causing kidney and urinary tract infections. B-group Ad infections often occur in immunocompromised patients, including AIDS patients, recipients of bone marrow transplants, or chemotherapy patients. Recent studies performed in U.S. military training facilities indicate an emergence of diverse species B serotypes at the majority of sites. This included the group 1 serotype 21 and the group 2 serotypes 3, 7, and 14. CD46-targeting vectors derived from Ad35 and Ad11 are important tools for in vitro gene transfer into human stem cells, including hematopoietic stem cells and induced pluripotent stem cells. Ad35 and Ad11 have been used as tools for cancer therapy, because CD46 appears to be uniformely overexpressed on many cancers. Furthermore, receptor X-targeting vectors, i.e vectors derived from Ad3 or vectors containing Ad3 fibers have shown superior in the transduction of tumor cells both in vitro and in vivo and are currently being used clinically in cancer patients. While extensive basic virology studies have been done on Ad5, the information of species B group 1 interaction with CD46 is limited. Furthermore, the receptor for a major subgroup of species B Ads (receptor X) is unknown. The goal of this thesis was it therefore to better understand virological and translational aspects of species B Ads. The specific findings described in this thesis include i) the identification of CD46 binding sites within the Ad35 fiber knob, ii) the study of the in vitro and in vivo properties of Ad vectors with increased affinity to CD46. iii) the study of the receptor usage of a newly emergent Ad14a, iv) the identification of desmoglein 2 as the receptor for Ad3, Ad7, Ad11, and Ad14, v) the delineation of structural details of Ad3 virus interaction with DSG2, and vi) the analysis of functional consequences of Ad3-DSG2 interaction. As a result of these basic virology studies two Ad-derived recombinant proteins have been generated that can be used to enhance cancer therapy by monoclonal antibodies.