Mais la polymyxine n'est pas du tout absorbée dans le sang du système gastro-intestinal et n'a d'effet que dans l'intestin et est utile pour le traitement des infections intestinales azithromycine prix Internet en y faisant des achats permettant d’économiser jusqu'à soixante-dix pour cent, tout en étant sûr de la qualité des produits pharmaceutiques.

A microporous lanthanide-organic framework

The total yield of the NAD adducts A ± E based on [7] D. A. Rozwarski, G. A. Grant, D. H. R. Barton, W. R. Jacobs, Jr., J. C.
consumed isoniazid is roughly 50% under the conditions Sacchettini, Science 1998, 279,98 ± 102.
shown in Figure 1 (micromolar concentrations of both iso- [8] F. Minisci, E. Vismara, F. Fontana, Heterocycles 1989, 28, 489 ± 519.
[9] Recombinant InhA was purified by using a N-terminal His-tag.[10] For niazid and NAD‡). The efficient formation of the inhibitor 2 the incubation experiments, InhA (5.4mm) was incubated with horse- in the absence of InhA is, in our opinion, of great importance radish peroxidase (44 mm), isoniazid (250mm), MnCl2 (7.5mm) and for an understanding of the mechanism of action of isoniazid.
either NAD‡ or NADH (each 47mm) at pH 7.5 (50mm Na2HPO4) and As the concentration of NAD‡ inside M. tuberculosis is also in 258C. The InhA activity was monitored by using a NADH-based assay.[6] After the activity dropped below 10% of the value at t the micromolar range,[15] we propose that inside the bacterium sample was dialyzed for 12 h at 4 8C in a microdialysis system 2 is formed by the fast addition of acyl radical 3 to electron- (GibcoBRL; Cut-off of the dialysis membrane: 12 ± 14 kD) against deficient heterocycles such as NAD‡ and outside the active 100 mm triethylammonium acetate, pH 7. MALDI-TOF spectra were site of InhA. Considering the low binding affinity of InhA for recorded by using a RP Biospectrometry Voyager DE; sinapinic acid, 2,5-dihydroxybenzoic acid, or 2-amino-5-nitropyridine were used as a I ˆ 4mm) and the resulting low concentration of InhA-bound NAD‡,[5] the also conceivable addition of 3 to [10] M. Wilming, Diploma thesis, Universität Bochum, 1998.
NAD‡ within the active site of InhA appears rather unlikely.
[11] HPLC analysis was performed on a Merck LiChroCART 250 ± 4 Furthermore, the catalase-peroxidase KatG does not play an Purospher RP-18e (5 mm) using a linear gradient from NH4OAc active role in the addition of 3 to NAD‡ (although it is (75 mm) to acetonitrile. UV spectra of the peaks were recorded using a required for oxidation of isoniazid), as the yield of isonico- tinoyl-NAD adducts as well as the product composition is I value of product B/E was determined by using 2-trans- octenoyl-CoA and NADH as substrates at pH 7.5 (100 mm Na2HPO4) about the same after oxidation of isoniazid by KatG or Mn3‡.
and 25 8C. At fixed concentrations of NADH and 2-trans-octenoyl- The mechanism of action of isoniazid therefore relies on CoA the concentration of B/E was varied.
the efficient formation of the isonicotinoyl ± NAD adducts [13] Y. Pocker, J. E. Meany, J. Am. Chem. Soc. 1967, 89, 631 ± 636.
[14] (4 ± 2H)-NAD‡ was synthesized according to the procedure of by a Minisci reaction as well as the inhibitory potential of Charlton et al.: P. A. Charlton, D. W. Young, B. Birdsall, J. Feeny, 2 (ˆB/E), whose KI value is about 100nm (see above) and G. C. K. Roberts, J. Chem. Soc. Perkin Trans. 1 1985, 1349 ± 1353.
therefore about a factor of 100 below the K [15] K. P. Gopinathan, M. Sirsi, T. Ramakrishnan, Biochem. J. 1963, 87, [16] a) L. Miesel, T. R. Weisbrod, J. A. Marcinkeviciene, R. Bittman, W. R.
The proposed reaction mechanism also allows one to Jacobs Jr., J. Bacteriol. 1998, 180, 2459 ± 2467; b) P. Chen, W. R. Bishai, reinterpret the observations that a number of isoniazid- Infect. Immun. 1998, 66, 5099 ± 5106.
resistant mycobacteria appear to possess a higher ratio of NADH/NAD‡ as the result of defects in NADH-dehydrogen- ases,[16a] and that overexpression of NAD‡-binding proteins might contribute to isoniazid-resistance.[16b] A lower intra- cellular concentration of NAD‡ should, according to our mechanism, directly lead to a diminished rate of formation of 2 and therefore to an increased resistance towards isoniazid.
In summary, the demonstrated spontaneous formation of the bioactive form of isoniazid significantly simplifies the proposed mechanism of action of the drug and should be helpful in obtaining a better understanding of the molecular The recent upsurge of reports on open metal ± organic events leading to isoniazid-resistance.
frameworks has provided compelling evidence for the ability to design and produce structures with unusual pore shape, size, composition, and function.[1] To realize the potential of these materials in host ± guest recognition, separation, and German version: Angew. Chem. 1999, 111, 2724 ± 2727 catalysis, it is essential that their frameworks exhibit perma- Keywords: bioorganic chemistry ´ cofactors ´ enzyme catal- [*] Prof. O. M. Yaghi,[‡] T. M. Reineke,[‡] Dr. M. Eddaoudi,[‡] [1] B. R. Bloom, C. J. L. Murray, Science 1992, 257, 1055 ± 1064.
[2] a) Y. Zhang, B. Heym, B. Allen, D. Young, S. Cole, Nature 1992, 258, Arizona State University, Box 871604, Tempe, AZ 85287 (USA) 591 ± 593; b) K. Johnsson, P. G. Schultz, J. Am. Chem. Soc. 1994, 116, [3] F. G. Winder, P. B. Collins, J. Gen. Microbiol. 1970, 63, 41 ± 48.
[4] a) A. Banerjee, E. Dubnau, A. Quemard, V. Balasubramanian, K.
Sun Um, T. Wilson, D. Collins, G. de Lisle, W. R. Jacobs, Jr., Science 1994, 263, 227 ± 230; b) K. Mdluli, R. A. Slayedn, Y. Zhu, S.
Ramaswamy, X. Pan, D. Mead, D. D. Crane, J. M. Musser, C. E.
[**] The financial support of this work by the National Science Foundation Barry III, Science 1998, 280, 1607 ± 1610.
(Grant CHE-9522303) and Department of Energy (Division of [5] A. Quemard, J. C. Sacchettini, A. Dessen, C. Vilcheze, R. Bittman, Chemical Sciences, Office of Basic Energy Sciences, Grant DE- W. R. Jacobs Jr., J. S. Blanchard, Biochemistry 1995, 34, 8235 ± 8241.
FG03-98ER14903), and the crystallographic work provided by Dr.
[6] K. Johnsson, D. S. King, P. G. Schultz, J. Am. Chem. Soc. 1995, 117, Fred Hollander (University of California-Berkeley) are gratefully  WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999 nent microporosity even in the absence of guests, an aspect that is routinely considered for zeolites[2] but has remained largely unexplored for the analogous metal ± organic materi- als.[3] In attempting to address this issue, we aimed at coupling our interest in designing new frameworks with the desire to achieve stable microporous structures. Here we report the synthesis and structure of Tb(bdc)NO3 ´ 2DMF (bdc ˆ 1,4- benzenedicarboxylate; DMF ˆ N,N-dimethylformamide) and show that its desolvated derivative Tb(bdc)NO3 has a stable zeolite-like framework that is capable of reversible molecular sorption and of maintaining microporosity in the absence of Previous studies on the copolymerization of ZnII with BDC have shown that stable frameworks can be produced.[3d, 4] This was attributed to the bis-bidentate functionality of BDC and its tendency to form large, tightly bound metal carboxylate cluster aggregates that ultimately act as building blocks in the crystal structure. We sought to extend this strategy to the pursuit of lanthanide ± organic open frameworks, which remain virtually unknown, despite the established role of lanthanide compounds sensor technology.[5] Deprotonation of the acid form of BDC (H2BDC) with pyridine followed by its copolymerization with TbIII in methanol/DMF at room temperature gave a crystalline color- less solid, which was formulated as Tb(bdc)NO3 ´ 2DMF on the basis of elemental analysis and single-crystal X-ray diffraction.[6, 7] Complete deprotonation of BDC was con- firmed by the absence of any strong absorption bands due to protonated carboxyl groups (1715 ± 1680 cmÀ1) in the FT-IR Figure 2. a) Tb ± BDC chains shown perpendicular to the c axis. b) A spectrum.[6] This material is stable in air and is insoluble in projection along the c axis with DMF shown in space-filling (C, shaded; N, common organic solvents such as methanol, ethanol, acetoni- cross-hatched; O, open) and the Tb ± BDC ± NO3 framework as ball-and- stick (Tb, filled; N, cross-hatched; C and O, open) representations.
Hydrogen atoms are omitted for clarity.
The single-crystal structure analysis revealed an extended Tb ± BDC framework with two crystallographically distinct Tb atoms, BDC units, nitrate ions, and four DMF ligands. The BDC to form a three-dimensional network (Figure 2b) in two Tb atoms are each coordinated by eight oxygen atoms: which the nitrate anions and DMF molecules point into the One each from four carboxylate groups of different BDC channels. The topology of the structure is best described in ligands, two from a nitrate anion, and one from each of two terms of a simple (3,4)-connected net derived from the DMF molecules (Figure 1). The framework is composed only 4-connected net of the PtS structure (Figure 3a and b). In this of Tb and BDC, whereby each carboxylate moiety bridges two case, each of the planar 4-connected vertices (filled circles) terbium atoms in a bis-monodentate fashion to form chains are split into pairs of 3-connected vertices that share a along the c axis (Figure 2a). These chains are cross-linked by common link.[8] As shown in Figure 3c, the 4-connected Figure 1. The asymmetric unit of crystalline Tb(bdc)NO3 ´ 2DMF; atoms labeled by the letter A are related by symmetry to those  WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999 195 K. When no further weight change was observed, a single isotherm point was recorded. A plot of weight sorbed per gram of Tb(bdc)NO3 versus p/p0 (p0 ˆ saturation pressure; 780 Torr for CO2) revealed a reversible type I isotherm (Figure 4), characteristic of a microporous material with Figure 3. a) The 4-connected net of PtS (S, open; Pt, filled). b) The (3,4)- connected net of Tb(bdc)NO3 ´ 2DMF that is derived from (a) by converting the planar 4-connected vertices (filled) to pairs of 3-connected vertices. c) Schematic identification of the atoms in the crystal structure of Tb(bdc)NO3 ´ 2DMF with net vertices; open circles are Tb atoms [4- connected vertices in (b)] and filled circles are carboxylate C atoms of BDC [3-connected vertices in (b)]; the benzene ring of BDC is super- imposed on the link between 3-connected vertices.
Figure 4. CO2 sorption (dark circles) and desorption (open circles) vertices are the Tb atoms which are connected through ÀOÀ isotherm for Tb(bdc)NO3 plotted with sorbed amount w versus relative links to the carboxylate C atoms of BDC (the 3-connected pressure p/p0 (p0 ˆ saturation pressure).
vertices); these are in turn joined in pairs by ÀC its highest symmetry form the network is tetragonal, space zeolite-like sorption behavior. The pore volume was estimat- group P42/mmc, but the symmetry is lower (P21/c) in the ed from this data by using the Dubinin ± Raduskhvich equation to be 0.032 cm3gÀ1, which is comparable to that of To create an open framework with accessible voids, we common zeolites.[2a] Applying the same technique at room examined the possibility of removing the DMF ligands by temperature for the vapor sorption, we found that dichloro- means of a thermogravimetric (TG) study. A sample of the as- methane (4 Š kinetic diameter) is readily sorbed into the synthesized material (46.87 mg) showed an onset of weight pores of Tb(bdc)NO3 with a type I isotherm. However, loss at 1208C that terminated at 2238C with 27.1% total weight sorption of cyclohexane was not observed due to its larger loss, which is equivalent to the removal of 1.97 DMF molecules per formula unit (calculated: 27.5%). The FT-IR The dissociation and removal of DMF from the channels spectrum of the remaining solid Tb(bdc)NO [9] means that terbium becomes coordinatively unsaturated in absorption bands to those of the original solid, albeit with the resulting porous solid. Exploring the chemistry of such minor differences due to the removal of DMF. Its X-ray Lewis acid sites may reveal their potential use in sensors or as powder diffraction pattern was significantly broadened with catalysts for organic transformations. On studying the solution only two discernible diffraction lines; this indicates a degra- stability of the porous framework, we observed that immer- dation of long-range order. However, the fact that sion of the evacuated solid in water results in its quantitative Tb(bdc)NO3 did not show any weight loss up to 3208C and irreversible conversion to another recently reported suggested the presence of a stable framework material. Re- porous solid, namely, Tb2(bdc)3 ´ 4H2O.[5a] Nevertheless, sorption of DMF into the solvent-free material resulted in Tb(bdc)NO3 appears to be unaffected by organic solvents, regeneration of the most prominent diffraction lines of the as- and this allowed allowed the study of its inclusion chemistry.
The solution sorption isotherms for methanol, ethanol, and To determine the microporosity of Tb(bdc)NO3, the gas isopropyl alcohol are shown in Figure 5. A known amount of sorption isotherm was measured. Initially, we confirmed the the evacuated solid (30 ± 40 mg) was immersed in a solution in loss of DMF from the original solid by placing a sample of toluene containing a specific amount of a potential guest Tb(bdc)NO3 ´ 2DMF (151.50 mg) in an electromicrogravimet- (0.10 ± 0.90m). The change in guest concentration was then ric balance (CAHN 1000) setup at room temperature under measured by gas chromatography with a thermal conductivity vacuum (5 Â 10À5 Torr). Then the loss of DMF was monitored detector. Each equilibrium point was obtained by monitoring by heating to 135 and 1858C at 0.15 KminÀ1. The total weight the change in guest concentration with time until no further losses of 18.68 (1.35DMF) and 26.97% (1.97DMF), respec- change was observed.[10] The sorption process was successfully tively, confirm the TG results. At this point, carbon dioxide modeled with a 1:1 complex as suggested by the Langmuir (UHP grade) was introduced into the sample chamber isotherm equation (assuming equivalent available sites), and containing the completely evacuated sample, and the weight all compounds showed good agreement to the model with changes were monitored at different pressure intervals at high nonlinear regression parameters (typically 0.99). The  WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999 Hoskins, J. Liu in Supramolecular Architecture: Synthetic Control in Thin Films and Solids (Ed.: T. Bein), American Chemical Society, Washington, DC, 1992, chap. 19; k) T. Iwamoto in Inclusion Com- pounds, Vol. 5 (Eds.: J. L. Atwood, J. Davies, D. D. MacNicol), Oxford University Press, New York, 1991, p.177.
[2] a) D. W. Breck in Zeolite Molecular Sieves, Structure, Chemistry, and Use, Wiley, New York, 1974; b) S. J. Gregg, K. S. W. Sing, Adsorption, Surface Area, Porosity, 2nd ed., Academic Press, London, 1982.
[3] a) S. A. Allison, R. M. Barrer, J. Chem. Soc. A 1969, 1717; b) D.
Ramprasad, G. P. Pez, B. H. Toby, T. J. Markley, R. M. Pearlstein, J.
Am. Chem. Soc. 1995, 117, 10 694; c) M. Kondo, T. Yoshitomi, K. Seki, H. Matsuzaka, S. Kitagawa, Angew. Chem. 1997, 109, 1844; Angew.
Chem. Int. Ed. Engl. 1997, 36, 1725; d) H. Li, M. Eddaoudi, T. L. Groy, O. M. Yaghi, J. Am. Chem. Soc. 1998, 120, 8571.
[4] H. Li, C. E. Davis, T. L. Groy, D. G. Kelley, O. M. Yaghi, J. Am. Chem.
[5] a) T. M. Reineke, M. Eddaoudi, M. Fehr, D. Kelley, O. M. Yaghi, J.
Figure 5. Room-temperature isotherms for the sorption of liquid alcohols Am. Chem. Soc. 1998, 121, 1999; b) Lanthanide Probes in Life, Chemical and Earth Sciences (Eds.: J.-C. G. Bünzli, G. R. Choppin), 3 . Molar ratio of guest to Tb(BDC)NO3 (y) versus equilibrium concentration of guest (x).
[6] Elemental analysis (%) calcd for C14H18O9N3Tb: Tb(bdc)(NO3) ´ 2DMF: C 31.65, H 3.42, N 7.91; found: C 31.33, H 3.35, N 7.90. FT- results show that the number of molecules sorbed per formula IR (KBr, 2000 ± 500 cmÀ1): nÄ ˆ 1702 (m), 1663 (vs), 1630 (s), 1591 (vs), unit decreases as the size of the guest increases, and a similar 1512 (w), 1440 (s), 1400 (vs), 1314 (s), 1255 (w), 1110 (m), 1064 (w), trend is observed for the association equilibrium constant K 1031 (w), 900 (w), 821 (m), 761 (s), 682 (m), 544 (m), 511 cmÀ1 (s). The europium analogue of this compound was also prepared by an (Figure 5). Both of these parameters indicate a size- and identical procedure and found to have the same composition and structure as the terbium compound. Elemental analysis (%) calcd for This study demonstrates that lanthanide carboxylate open C14H18O9N3Eu: Eu(bdc)(NO3) ´ 2DMF: C 32.07, H 3.46, N 8.01; frameworks can have sufficient stability to support zeolite- like microporosity. Current studies are focused on exploring [7] An X-ray single-crystal analysis was performed on a colorless the accessibility of the Lewis acid metal sites within the sions of 0.07  0.16  0.19 mm at À 115 Æ 18C: monoclinic, space group channels and the design of analogous frameworks with larger P21/c, a ˆ 17.5986(1), b ˆ 19.9964(3), c ˆ 10.5454(2) Š, b ˆ 91.283(1)8, V ˆ 3710.09(7) Š3, Z ˆ 8, 1calcd ˆ 1.90 gcmÀ3; m(MoKa) ˆ 38.57 mmÀ1.
All measurements were made on a SMART CCD area detector with graphite-monochromated MoKa radiation. Frames corresponding to an arbitrary hemisphere of data were collected by w scans of 0.308 counted for a total 10.0 s per frame. Cell constants and an orientation matrix, obtained from a least-square refinement of the measured positions of 7766 reflections in the range 3.00 ` 2q ` 45.008 corre- 3 ´ 2 DMF : 1,4-benzenedicarboxylic acid (H2BDC) (0.050 g, 0.30 mmol) and terbium(iii) nitrate pentahydrate (0.131 g, 0.30 mmol) sponded to a primitive monoclinic cell. Data were integrated by the were placed in a small vial and dissolved in a mixture of methanol (3 mL) program SAINT[11] to a maximum 2q value of 49.58 and corrected for and DMF (3 mL) with mild heating. The vial was then placed in a larger vial Lorentzian and polarization effects by using XPREP[12]. The data containing pyridine (4 mL), which was sealed and left undisturbed for 5 d at were corrected for absorption by comparison of redundant and room temperature. The resulting colorless block-shaped crystals were equivalent reflections by using SADABS[13] (Tmax ˆ 0.74, Tmin ˆ 0.47).
collected by filtration, washed with methanol (3  10 mL), and air dried to The structure was solved by direct methods. Terbium and oxygen atoms were refined with anisotropic displacement parameters, and 3 ´ 2 DMF (0.12 g, 73 % yield). The isostructural europium analogue was prepared by a similar procedure from europium(iii) nitrate carbon atoms with isotropic parameters. Hydrogen atoms of the organic ligands were included but not refined. The final cycle of full- matrix least-squares refinement was based on 3156 observed reflec- tions (I b 3.00s(I)) and 227 variables and refined to convergence R1 ˆ German version: Angew. Chem. 1999, 111, 2712 ± 2716 0.058 (unweighted, based on F)and Rw ˆ 0.065. The maximum and minimum peaks on the final difference Fourier map corresponded to Keywords: host ± guest chemistry ´ lanthanides ´ micro- 5.19 and À1.87 eÀ ŠÀ3, respectively. Crystallographic data (excluding structure factors) for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-119758. Copies of the data can be obtained free of charge on application to CCDC, 12 Union [1] a) D. M. L. Goodgame, D. A. Grachvogel, D. J. Williams, Angew.
Road, Cambridge CB21EZ, UK (fax: (‡44)1223-336-033; e-mail: Chem. 1999, 111, 217; Angew. Chem. Int. Ed. 1999, 38, 153; b) O. M.
Yaghi, H. Li, C. Davis, D. Richardson, T. L. Groy, Acc. Chem. Res.
[8] Generation of 3- and (3,4)-connected nets from 4-connected nets: M.
1998, 31, 874; c) J. Lu, T. Paliwala, S. C. Lim, C. Yu, T. Niu, A. J.
OKeeffe, B. G. Hyde, Crystal Structures I: Patterns and Symmetry, Jacobson, Inorg. Chem. 1997, 36, 923; d) C. Janiak, Angew. Chem. 1997, Mineralogical Society of America, Washington, DC, 1996, p. 359.
109, 1499; Angew. Chem. Int. Ed. Engl. 1997, 36, 1431; e) P. Losier, [9] Elemental analysis (%) calcd for C8H4O7NTb: Tb(bdc)(NO3) C 24.95, M. J. Zaworotko, Angew. Chem. 1996, 108, 2957; Angew. Chem. Int.
H 1.05, N 3.64; found: C 25.37, H 1.31, N 3.95. FT-IR (KBr, 2000 ± Ed. Engl. 1996, 35, 2779; f) G. B. Gardner, D. Venkataraman, J. S.
500 cmÀ1): nÄ ˆ 1630 (m), 1564 (s), 1512 (m), 1387 (vs), 1320 (w), 1163 Moore, S. Lee, Nature 1995, 374, 792; g) O. Yaghi, G. Li, H. Li, Nature (w), 1117 (w), 1025 (w), 893 (w), 847 (w), 814 (w), 761 (m), 518 cmÀ1 1995, 378, 703; h) M. Fujita, Y. J. Kwon, O. Sasaki, K. Yamaguchi, K.
(m). When this material is exposed to DMF vapor for 1 d, the original Ogura, J. Am. Chem. Soc. 1995, 117, 7287; i) L. Carlucci, G. Ciani, product is regenerated. Elemental analysis (%) calcd for the D. M. Proserpio, A. Sironi, J. Chem. Soc. Chem. Commun. 1994, 2755; regenerated product C14H18O9N3Tb: Tb(bdc)(NO3) ´ 2DMF: C 31.65, j) R. Robson, B. F. Abrahams, S. R. Batteen, R. W. Gable, B. F.
H 3.42, N 7.91; found: C 31.40, H 3.44, N 7.88.
 WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999 [10] A standard solution containing the same guest concentration was cally behaves like iodine azide (3b). Since the pioneering periodically checked with the same techniques employed for each work of Hassner et al.[12] azido-iodination of alkene double experiment. To further show that the alcohol guests were included bonds has become a very useful procedure for introducing a within the pores rather than on the crystal surface, the GC sample was filtered, washed with toluene, air dried, and then elemental micro- nitrogen functionality into a carbon skeleton. Iodine azide analysis was performed to confirm the presence of alcohol.
(3b) has commonly been generated in situ from sodium azide [11] SAX Area-Detector Integration Program (SAINT), V4.024, Siemens and iodine chloride in polar solvents.[12, 13] However, its Industrial Automation, Inc., Madison, WI, 1995.
explosive character is regarded to be a major disadvantage.
[12] XPREP, V 5.03, is part of the program SHELXTL Crystal Structure Our approach to iodine azide (3b) is based on the reaction Determination, Siemens Industrial Automation, Inc., Madison, WI, of (diacetoxyiodo)benzene with polystyrene-bound iodide [13] Siemens Area Detector ABSorption correction program (SADABS), 1 in dichloromethane at room temperature, which presum- G. Sheldrick, personal communication, 1996.
ably afforded polymer-bound di(acetyloxy)iodate(i) (2) (Scheme 1).[14, 15] Treatment of 2 with trimethylsilylazide furnished a resin which synthetically acts like immobilized iodine azide (3b). However, extensive washing of the resin does not result in deactivation thus we propose that polymer- bound bis(azido)iodate(i) (3a) is the active species. Reagent Stable Polymer-Bound Iodine Azide**Andreas Kirschning,* Holger Monenschein, and In addition to numerous methods for the syntheses of organic molecules on polymeric supports, there has been a recent upsurge in the interest in the use of polymer-bound reagents in organic chemistry.[1] The intrinsic advantage of this hybrid solid-/solution-phase technique lies in the simple work- up and isolation of the reaction products combined with the Scheme 1. Preperation of novel polymer-bound iodine azide.
flexibility of solution-phase chemistry. Furthermore, these reagents may be used in excess in order to drive the reaction to completion without making the isolation of the products 3a may also be generated by direct azido transfer after more difficult. Although stoichometric polymer-supported treatment of iodide 1 with (diazidoiodo)benzene. However, as reagents have been employed in organic synthesis for many PhI(N3)2 has to be prepared in situ from (diacetoxyiodo)ben- years, their application to the construction of small molecule zene and trimethylsilylazide efficient azido transfer to 1 is libraries is a relative recent phenomenon. This can be ascribed hampered by the presence of trimethylsilyl acetate in solution.
to the fact that the number of readily available reagents of this The IR spectrum of the new polymer 3a shows a pair of strong type is still small. Important developments in this field are bands at nÄ ˆ 2010 and 1943 cmÀ1, which confirm the presence polymer-supported reductants,[2] oxidants,[3] solution-phase of an azido group. It smoothly promotes azido-iodination of scavengers,[4] chelating proton donors,[5] carbodimide equiv- alkenes 4 ± 18 to give the anti addition product (Table 1).[16] alents,[6] or reagents that are capable of promoting CÀC bond- Except for electron-defficient alkenes 5 and 11 and for forming reactions.[7] However, polymer-bound reagents for methylenecyclopropane 17 (Table 1), sensitive b-iodo azides 1,2-cohalogentions[8, 9] of alkenes have not been described so 19, 21 ± 25, and 27 ± 33 are generated in good to excellent yield. They are conveniently purified by filtration and As an extension of our earlier work on ligand-transfer removal of the solvent.[17] The regioselectivity of the 1,2- reactions from hypervalent iodine(iii) reagents to halides in addition is governed by the more stable intermediate carben- solution,[11] we initiated a study on the development of the ium ion formed after electrophilic attack. Only when alkyl- first stable electrophilic polymer-bound reagent that syntheti- substituted alkenes 15 and 16 were subjected to the azido- iodination conditions, were small amounts of the anti- Markovnikov 1,2-adducts formed. Remarkably, free hydroxy groups in allyl or homoallyl position, such as in alkenes 7, 13, Institut für Organische Chemie der Technische Universität Clausthal Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld (Germany) and 14, are tolerated under the conditions employed. Addi- tion to methylenecyclopropane 17 proceeded in a highly E-mail: [email protected] regioselective and stereoselective manner to furnish 32.
Rearrangement products which may have originated from Bayer AG, Business Group Pharma PH-R-CR, D-42096 Wuppertal the very stable intermediate cyclopropylmethyl cation[18] were not isolated. The relative configuration of 32 was uneqivocally [**] This work was supported by the Fonds der Chemischen Industrie. We thank Bayer AG and particularly Dr. D. Häbich (Wuppertal) for assigned by nuclear Overhauser effect (NOE) experiments (Table 2). Finally, also 1,2-functionalization of carbohydrate-  WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999


Volantino tour siria

COMUNE DI MEDIGLIA SOGGIORNI TOUR CLASSICO “SUPERIOR” 5 STELLE dal 13/04/2011 al 20/04/2011 Prenotarsi entro il giorno 30 GENNAIO 2011 validità di almeno sei mesi dalla data di partenza. il visto è gratuito ed è ottenibile in loco. IMPORTANTE*** per l’ottenimento del visto di ingresso è indispensabile inviare i dati anagrafici, MINIMO PARTECIPANTI: 16

Mcq- reproduction

MCQ – Respiration Answers are shown in Bold 1.Simple binary fission is found in a. Paramecium b. Sponge c. Euglena d. Amoeba a. Simple binary fission b. Transverse binary fission c. Longitudinal binary fission d. Oblique binary fission 3. Which of the following animal show Longitudinal binary fission a. Euglena and Vorticella b. Opalina and Monocystis c. Volvox and Chlamydomonas d.

Copyright © 2010-2014 Medical Science