Synthesis and biological evaluation of 2,4-diaminopteridine derivatives as nitric oxide synthase inhibitor

A series of novel 2,4-diamino-pteridines(9a-1)were synthesized and evaluated as inhibitors of inducible nitric oxide synthase (iNOS)in vitro.It was found that 9a,9d,9e,9h,9i and 91 showed potent inhibitory activities similar to that of methotrexate(MTX),while the activities of 9b,9c,9f,9g,9j and 9k ale stronger than MTX.     

Multi-carbazole derivatives for two-photon absorption data storage:Synthesis,optical properties and theoretical calculation

Two novel quadrupolar organic compounds, 3-(4-((E)-2-(9-butyl-9H-carbazol-6-yl) vinyl)styryl)-9-propyl-9H-carbazole (BCSPC) and 3-(3-(3-((1E)-2-(4-((E)-2-(3-(3,5-bis(9-butyl-9H-carbazol-6-yl)phenyl)-9-butyl-9H-carbazol-6-yl)vinyl)phenyl) vinyl)-9-butyl-9H-carbazol-6-yl)-5-(9-butyl-9H-carbazol-6-yl)phenyl)-9-butyl-9H-carbazole (BCPBC), with different conjugated arms, have been designed and synthesized. Their one-and two-photon absorption (TPA) and excited fluorescence properties have been experimentally inve...     

Préparation de la 8,14-diméthyl 18-nor-testostérone

Les sécrétions de 4 espèces de Dipterocarpus Viêt-Namiens ont fourni un triterpène tétracyclique, identifié au diptérocarpol de van Itallie et à l'hydroxy-dammarénone-II (I) de Mills. Le diptérocarpol est dégradé (chaîne latérale) et modifié (cycle A) en un analogue de la testostérone (XXX). Sa stéréochimie est discutée.     

Design,Synthesis, and Biological Evaluation of New 8‐Trifluoromethylquinoline Containing Pyrazole‐3‐carboxamide Derivatives

The article describes the design, synthesis, and characterization of a new series of 8‐trifluoromethylquinoline substituted pyrazole‐3‐carboxamides ( 9a , 9b , 9c , 9d , 9e , 9f , 9g , 9h , 9i , 9j , 9k , 9l , 9m , 9n , 9o , 9p , 9q , 9r , 9s , 9t ) derived from different primary and secondary amines. The intermediate and target compounds were characterized using spectroscopic methods. The structures of intermediate 7 and target molecule 9d were evidenced by the single crystal X‐ray study. All the synthesized target compounds ( 9a , 9b , 9c , 9d , 9e , 9f , 9g , 9h , 9i , 9j , 9k , 9l , 9m , 9n , 9o , 9p , 9q , 9r , 9s , 9t ) and three intermediates ( 6 , 7 , 8 ) were screened for their in vitro antitubercular activity against Mycobacterium tuberculosis H₃₇Rv strain. Two compounds, 9k and 9t , showed significant inhibition activity with MIC of 3.13 µg/mL, which is comparable with the activity of standard drug, ethambutol. The carboxamides derived from benzylamine derivatives were more active than their aniline analogs. In general, the hybrid amides with a N‐methylene linkage (‐CONHCH₂‐) exhibited enhanced antitubercular activity. In the antibacterial screening, intermediate 3‐hydrazinyl‐2‐methyl‐8‐(trifluoromethyl)quinoline ( 6 ) displayed remarkable activity against the tested bacterial strains. Further, the active anti‐TB derivatives were non‐toxic to benign NIH 3T3 cells, which demonstrate the lack of general cellular toxicity and hence signifies their suitability for further lead development.     

Solvent-mediated generation of cobalt-cluster-stabilised propargyl cations and radicals: allyl migration versus peroxide formation

The protonation of [Co(2)(CO)(6){9-[(allyldimethylsilyl)ethynyl]-9H-fluoren-9-ol}] (4), with HBF(4) in CH(2)Cl(2) led to migration of the allyl group from silicon to the cobalt-stabilised cationic site to furnish [Co(2)(CO)(6){9-allyl-9-[(dimethylfluorosilyl)ethynyl]-9H-fluorene}] (17). However, under the same conditions, [Co(2)(CO)(6){9-[(benzyldimethylsilyl)ethynyl]-9H-fluoren-9-ol}] (5) underwent desilylation and rearrangement of the resulting terminal alkyne-dicobalt complex to give [Co(3)(CO)(9)(9H-fluorenylmethylcarbynyl)] (24); moreover, dimerisation of the (benzyldimethylsilyl)ethynyl-9H-fluorenyl moiety led to the propargyl-allene 26. In contrast, protonation of 5 in THF yielded [{Co(2)(CO)(6){[(benzyldimethylsilyl)ethynyl-9H-fluorenyl])}(2)peroxide] (27) through a radical coupling process. Analogously, protonation of [Co(2)(CO)(6){9-[(vinyldimethylsilyl)ethynyl]-9H-fluoren-9-ol}] (6) yields the corresponding peroxide 28. X-ray crystallographic data are reported for, among others, complexes 17, 24, 26, 27 and 28.     

Overcrowded 1,8-diazafluorenylidene-chalcoxanthenes. Introducing nitrogens at the fjord regions of bistricyclic aromatic enes

The effects of introducing nitrogen atoms in the fjord regions and chalcogen bridges on the conformations of overcrowded bistricyclic aromatic enes (1, X not equal to Y) (BAEs) were studied. 9-(9'H-1',8'-Diazafluoren-9'-ylidene)-9H-thioxanthene (12), 9-(9H-1',8'-diazafluoren-9'-ylidene)-9H-selenoxanthene (13), 9-(9'H-1',8'-diazafluoren-9'-ylidene)-9H-telluroxanthene (14), 9-(9' H-1',8'-fluoren-9-ylidene)-9H-xanthene (15) and 9-(9' H-1',8'-fluoren-9'-ylidene)-9H-fluorene (16) were synthesized by two-fold extrusion coupling reactions of 1,8-diaza-9H-fluoren-9-one (19)/chalcoxanthenthiones (24-27) (or /9H-fluorene-9-thione (30)). The 1',8'-diazafluoren-9-ylidene-chalcoxanthenes (11) were compared with the respective fluoren-9-ylidene-chalcoxanthenes (10). The structures of 12-16 were established by 1H, 13C, 77Se, and 125Te NMR spectroscopies. The crystal and molecular structures of 12-14 were determined by X-ray analysis. The yellow molecules of 12-14 adopted mono-folded conformations with folding dihedrals in the chalocoxanthylidene moieties of 62.7 degrees (12), 62.4 degrees (13) and 59.9 degrees (14). The folding dihedrals in the respective 1',8'-diazafluorenylidene moieties were very small, ca. 2 degrees, compared with 10.2/8.0 degrees in (9'H-fluoren-9'-ylidene)-9H-selenoxanthene (7). A 5 degree pure twist of C9=C9' in 14 is noted. The degrees of overcrowding in the fjord regions of 12-14 (intramolecular non-bonding distances) were relatively small. The degrees of pyramidalization of C9 and C9' were 17.0/3.0 degrees (12), 17.4/2.4 degrees (13) and 2.2/2.2 degrees (14). These high values in 12 and 13 stem from the resistance of the 1.8-diazafluorenylidene moiety to fold and from the limits in the degrees of folding of the thioxanthylidene and selenoxanthylidene moieties (due to shorter S10-C4a/S10-C10a and Se10-C4a/Se10-C10a bonds, as compared with the respective Te-C bonds in 14). The molecules of 15 and 16 adopt twisted conformations, a conclusion drawn from the 1H NMR chemical shifts of the fjord regions protons (H1 and H8) at 8.70 (15) and 9.00 ppm (16) and from their colors and UV/VIS spectra: 15 is purple (lambdamax = 521 nm) and 16 is orange-red. A comparison of the NMR spectra of 11 and 10 (deltadelta = delta(11) -delta(10)) showed substantial downfield shifts of 0.56-0.62 ppm of the fjord regions protons of twisted 15 and 16: deltadelta (C9) were negative (upfield): -4.0 (12), -3.7 (13), -3.4 (14), -7.1 (15), -5.0 ppm (16), while deltadelta (C9') were positive (downfield) = +6.8 (12), +6.5 (13), +5.8 (14), + 11.7 (15), +7.7 ppm (16). In 15, deltadelta (C9) - deltadelta (C9') = + 18.8 ppm, attributed to a push-pull character and significant contributions of zwitterionic structures in the twisted conformation. The 77Se and 125Te NMR signals of 13 and 14 were shifted upfield relative to the respective fluorenylidene-chalcoxanthene derivatives: deltadelta77Se = 17.2 ppm and deltadelta125Te = 22.0 ppm. The presence of the nitrogen atoms (N1' and N8') in 13 and 14 causes shielding of the selenium and tellurium nuclei.     

Probing the limits of the Zintl concept: structure and bonding in rare-earth and alkaline-earth zinc-antimonides Yb9Zn4+xSb9 and Ca9Zn4.5Sb9

A new transition metal Zintl phase, Yb(9)Zn(4+x)Sb(9), was prepared by high-temperature flux syntheses as large single crystals, or by direct fusion of the corresponding elements in polycrystalline form. Its crystal structure was determined by single-crystal X-ray diffraction. Its Ca-counterpart, hitherto known as Ca(9)Zn(4)Sb(9), and the presence of nonstoichiometry in it were also studied. Yb(9)Zn(4+x)Sb(9) was found to exist in a narrow homogeneity range, as suggested from the crystallographic data at 90(3) K (orthorhombic, space group Pbam (No. 55), Z = 2): (1) a = 21.677(2) A, b = 12.3223(10) A, c = 4.5259(4) A, R1 = 3.09%, wR2 = 7.18% for Yb(9)Zn(4.23(2))Sb(9); (2) a = 21.706(2) A, b = 12.3381(13) A, c = 4.5297(5) A, R1 = 2.98%, wR2 = 5.63% for Yb(9)Zn(4.380(12))Sb(9); and (3) a = 21.700(2) A, b = 12.3400(9) A, c = 4.5339(4) A, R1 = 2.75%, wR2 = 5.65% for Yb(9)Zn(4.384(14))Sb(9). The isostructural Ca(9)Zn(4.478(8))Sb(9) has unit cell parameters a = 21.830(2) A, b = 12.4476(9) A, and c = 4.5414(3) A (R1 = 3.33%, wR2 = 5.83%). The structure type in which these compounds crystallize is related to the Ca(9)Mn(4)Bi(9) type, and can be considered an interstitially stabilized variant. Formal electron count suggests that the Yb or Ca cations are in the +2 oxidation state. This is supported by the virtually temperature-independent magnetization for Yb(9)Zn(4.5)Sb(9). Electrical resistivity data show that Yb(9)Zn(4.5)Sb(9) and Ca(9)Zn(4.5)Sb(9) are poor metals with room-temperature resistivity of 10.2 and 19.6 mOmega.cm, respectively.     

Eine kinetische analysenmethode unter verwendung katalysierter systeme im stationären zustand Die bestimmung von jodid, osmium, quecksilber, silber und l-cystin im p.p.b.-p.p.m.-bereich

A new kinetic method of analysis based on catalysed reactions is described. The principle is as follows: to a reaction mixture containing the catalyst to be determined and a large excess of one reactant is added the other reactant at a constant rate; the concentration of the second reactant reaches a steady-state value which can be measured to provide a measure of the catalyst concentration. Iodide and osmium were determined in the p.p.b. range by their catalytic effect on the cerium(IV)-arsenic(III) reaction, the cerium(IV) concentration in the steady state being determined photometrically. Mercury(II) and silver(I) prevent the catalytic action of iodide and so can be determined indirectly. L-Cystine was determined in the p.p.m. range by means of its catalytic action on the iodine-azide reaction; the iodine concentration prevailing in the steady state was followed potentiometrically.

Résumé

On décrit une nouvelle méthode d'analyse cinétique, basée sur des réactions de catalyse: on ajoute, à un mélange contenant catalyseur à doser et un réactant en grand excès, l'autre réactant à vitesse constante. La concentration en catalyseur est fonction de la quantité du deuxième réactant nécessaire pour atteindre une valeur constante. Iodure et osmium, en quantité de l'ordre du p.p.b., ont pu être dosés grâce ù leur effet catalytique sur la réaction cérium(IV) -arsenic(III) ; la concentration en cérium(IV) est déterminée par photométrie. Mercure(II) et argent(I) empêchent l'action catalytique de l'iodure et peuvent être dosés indirectement. La L-cystine est dosée grâce à son action catalytique sur la réaction iode-azoture. La concentration en iode est déterminée par potentiométrie.     

Surprising acid/base and ion-sequestration chemistry of Sn9(4-): HSn9(3-), Ni@HSn9(3-), and the Sn9(3-) ion revisited

K(4)Sn(9) dissolves in ethylenediamine (en) to give equilibrium mixtures of the diamagnetic HSn(9)(3-) ion along with K(x)Sn(9)((4-x)-) ion pairs, where x = 0, 1, 2, 3. The HSn(9)(3-) cluster is formed from the deprotonation of the en solvent and is the conjugate acid of Sn(9)(4-). DFT studies show that the structure is quite similar to the known isoelectronic RSn(9)(3-) ions (e.g., R = i-Pr). The hydrogen atom of HSn(9)(3-) (δ = 6.18 ppm) rapidly migrates among all nine Sn atoms in an intramolecular fashion; the Sn(9) core is also highly dynamic on the NMR time scale. The HSn(9)(3-) cluster reacts with Ni(cod)(2) to give the Ni@HSn(9)(3-) ion containing a hydridic hydrogen (δ = -28.3 ppm) that also scrambles across the Sn(9) cluster. The Sn(9)(4-) ion competes effectively with 2,2,2-crypt for binding K(+) in en solutions, and the pK(a) of HSn(9)(3-) is similar to that of en (i.e., Sn(9)(4-) is a very strong Br?nsted base with a pK(b) comparable to that of the NH(2)CH(2)CH(2)NH(-) anion). Competition studies show that the HSn(9)(3-) ? Sn(9)(4-) + H(+) equilibrium is fully reversible. The HSn(9)(3-) anion is present in significant concentrations in en solutions containing 2,2,2-crypt, yet it has gone undetected for over 30 years.     

Synthesis and hydrolysis of p‐toluoyl and acetyl 9‐triptycyl diselenides: A study on generation of triptycene‐9‐selenenoselenoic acid

p‐Toluoyl 9‐triptycyl diselenide ( 9 ) was prepared by reaction of Se‐9‐triptycyl triptycene‐9‐selenoseleninate ( 7 ) with p‐toluenecarboselenoic acid ( 8 ) and by reaction of triptycene‐9‐selenenoselenolate salt with p‐toluoyl chloride. Acetyl 9‐triptycyl diselenide ( 13 ) was prepared by reaction of triptycene‐9‐selenenoselenolate salt with acetyl chloride. Hydrolysis of the two diselenides, 9 and 13 , provided triptycene‐9‐selenol ( 10 ) and di‐9‐triptycyl triselenide ( 12 ), suggesting the generation of triptycene‐9‐selenenoselenoic acid ( 3 ). © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:525–528, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20155     

Monocarbaborane anion chemistry. [COOH], [CH2OH] and [CHO] units as functional groups on ten-vertex monocarbaborane anionic compounds

B(10)H(14) reacts with para-C(6)H(4)(CHO)(COOH) in aqueous KOH solution to give the [nido-6-CB(9)H(11)-6-(C(6)H(4)-para-COOH)](-) anion 1, which undergoes cage closure with iodine in alkaline solution to give the [closo-2-CB(9)H(9)-2-(C(6)H(4)-para-COOH)](-) anion 2. Upon heating, anion 2 rearranges to form the [closo-1-CB(9)H(9)-1-(C(6)H(4)-para-COOH)](-) anion 3. Similarly, B(10)H(14) with glyoxylic acid OHCCOOH in aqueous KOH gives the [arachno-6-CB(9)H(13)-6-(COOH)](-) anion 4, which undergoes cage closure with iodine in alkaline solution to give the [closo-2-CB(9)H(9)-2-(COOH)](-) anion 5. Upon heating, anion 5 rearranges to give the [closo-1-CB(9)H(9)-1-(COOH)](-) anion 6. Reduction of the [COOH] anions 3 and 6 with diisobutylaluminium hydride gives the [CH(2)OH] hydroxy anions [closo-1-CB(9)H(9)-1-(C(6)H(4)-para-CH(2)OH)](-) and [closo-1-CB(9)H(9)-1-(CH(2)OH)](-) 8 respectively. The [closo-1-CB(9)H(9)-1-(C(6)H(4)-para-CH(2)OH)](-) anion 7 can also be made via isomerisation of the [closo-2-CB(9)H(9)-2-(C(6)H(4)-para-CH(2)OH)](-) anion 9, in turn obtained from the [nido-6-CB(9)H(11)-6-(C(6)H(4)-para-CH(2)OH)](-) anion 10, which is obtained from the reaction of B(10)H(14) with terephthaldicarboxaldehyde, C(6)H(4)-para-(CHO)(2), in aqueous KOH solution. Oxidation of the hydroxy anions 7 and 8 with pyridinium dichromate gives the aldehydic [closo-1-CB(9)H(9)-1-(C(6)H(4)-para-CHO)](-) anion 11 and the aldehydic [closo-1-CB(9)H(9)-1-(CHO)](-) anion 12 respectively, characterised as their 2,4-dinitrophenylhydrazone derivatives, the [closo-1-CB(9)H(9)-1-C(6)H(4)-para-CH=N-NHC(6)H(3)(NO(2))(2)](-) anion 13 and the [closo-1-CB(9)H(9)-1-CH=N-NHC(6)H(3)(NO(2))(2)](-) anion respectively.     

Association patterns of platinated purine nucleobases in metal-modified pairs and triples

Blocking of Watson-Crick or Hoogsteen edges in purine nucleobases by a metal entity precludes involvement of these sites in interbase hydrogen bonding, thereby leaving the respective other edge or the sugar edge as potential H bonding sites. In mixed guanine, adenine complexes of trans-a2PtII (a = NH3 or CH3NH2) of composition trans-[(NH3)2Pt(9-EtA-N1)(9-MeGH-N7)](NO3)2 (1a), trans-[(NH3)2Pt(9-EtA-N1)(9-MeGH-N7)](ClO4)2 (1b), and trans,trans-[(CH3NH2)2(9-MeGH-N7)Pt(N1-9-MeA-N7)Pt(9-MeGH-N7)(CH3NH2)2](ClO4)4*2H2O (2) (with 9-EtA = 9-ethyladenine, 9-MeA= 9-methyladenine, 9-MeGH = 9-methylguanine), this aspect is studied. Thus, in 1b pairing of two adenine ligands via Hoogsteen edges and in 2 pairing of two guanine bases via sugar edges is realized. These situations are compared with those found in a series of related complexes.     

The elusive vanadate (V(3)O(9))(3-): isolation, crystal structure, and nonaqueous solution behavior.

The isolation, crystal structure, and nonaqueous solution characteristics of the first trinuclear vanadate are presented. The crystal structure reveals a six-membered cyclic arrangement of alternating vanadium and oxygen atoms for the anion of [(C(4)H(9))(4)N](3)(V(3)O(9)). The (51)V NMR spectrum of this compound in CD(3)CN exhibits multiple peaks. The relative intensities of each resonance can be altered by concentration and temperature changes, the later of which are reversible. Addition of [(C(4)H(9))(4)N]Br and NaClO(4) also perturbs the equilibria between species observed. Conductivity data for [(C(4)H(9))(4)N](3)(V(3)O(9)) in CH(3)CN as a function of concentration display pronounced curvature and indicate formation of a neutral species in solution at the highest concentrations studied. Stoichiometric mixtures of [(C(4)H(9))(4)N](3)(V(3)O(9)) with the known vanadates [(C(4)H(9))(4)N](3)(HV(4)O(12)), [(C(4)H(9))(4)N](3)(V(5)O(14)), and [(C(4)H(9))(4)N](3)(H(3)V(10)O(28)) are prepared and examined by (51)V NMR. Equilibration between the various vanadates is observed and characterized. Resonances for these known vanadates, however, cannot be used to identify the peaks found for [(C(4)H(9))(4)N](3)(V(3)O(9)), alone, in solution. The existence of ion pairs in acetonitrile is the only interpretation for the solution behavior of [(C(4)H(9))(4)N](3)(V(3)O(9)) consistent with all data. As such, we can directly observe each possible ion pairing state by (51)V NMR: (V(3)O(9))(3-) at -555 ppm, [[(C(4)H(9))(4)N](V(3)O(9))] (2-) at -569 ppm, [[(C(4)H(9))(4)N](2)(V(3)O(9))](-) at -576 ppm, and [(C(4)H(9))(4)N](3)(V(3)O(9)) at -628 ppm. To the best of our knowledge, [(C(4)H(9))(4)N](3)(V(3)O(9)) presents the first case in which every possible ion paired state can be observed directly from a parent polyion. Isolation and characterization of this simple metal oxo moiety may now facilitate efforts to design functional polyoxometalates.     

Etudes theoriques de molecules interstellaires soufrees

The potential value of quantum chemical methods in the study of interstellar molecules is illustrated by ab initio calculations on sulphur compounds of astrophysical interest. This work includes: (1) assignments of rotation lines from “non-terrestrial” molecules (i.e., those for which laboratory spectra were lacking, such as the HCS⁺ ion and its metastable isomer HSC⁺), through structure computations; (2) energy balances for the formation and dissociation reactions of protonated species from simpler sulphur-containing molecules, and (3) a determination of the energy curves for the first Σ and Π states of the (H---S)⁺ system, to be used later in a collision treatment of the charge-exchange reaction between the sulphur and hydrogen atoms. ab]Lea possibilités deg méthodes de la chimie quantique dans le domaine des molécules interstellaires sont illustrées par des calculs relatifs á des composés soufrés d'intérêt astrophysique. Les recherches effectuées comprennent: (1) des attributions de raies de rotation provenant de molécules “non-terrestres” (c'est à dire de composés pour lesquels on manquait de données de laboratoire, tels l'ion HCS⁺ et son isomzère métastable (HSC⁺), à l'aide de calculs de structure; (2) des évaluations de bilans énerg étiques pour lea réactions de formation et de destruction des espcés protonés dans l'espace à partir de molécules soufrées plus simples, et (3) une détermination des courbes d'énergle des premiers états Σ et Π du système (H---S)⁺ pour une étude collisionnelle ult erieure de la réaction d'échange de charge entre les atomes de soufre et d'hydrogène.     

Mixed-crystal packing calculations. 9-methoxyanthracene in host 9-cyanoanthracene

Packing calculations by the atom-atom interaction method are reported for 9-methoxyanthracene (9MeOA) as a guest in host crystalline 9-cyanoanthracene (9CNA). The lower-energy local packing has approximately parallel anthracene nuclei, and substituents in head-to-head (“cis”) registry, in agreement with the structure found experimentally for the photochemical 9MeOA-9CNA complex. Electronic excitation of a host 9CNA adjacent to the guest 9MeOA causes an impulsive, short-lived, displacement of 9CNA*, giving dynamic preformation of either (9CNA)₂ excimer, or 9CNA-9MeOA exciplex. Over longer times, the structural response to excitation is followed by calculations including the successive relaxation of neighbour molecules, converging to an equilibrium structure for the locally excited crystal.     

Direkte komplexometrische eisenbestimmung mit xylenolorange als indikator

The complexometric determination of iron^III, based on a new end-point procedure, has been developed. Xylenol orange was used as the indicator. This forms a stable violet-blue complex. By the addition of iron^II to the titrated solution the usual displacement reaction at the end-point of the titration is replaced by a redox process which gives a very sharp end-point. The new procedure makes possible an accurate and very selective determination of iron^III. Only bismuth, thallium^III and large amounts of copper require to be removed before the titration.

Résumé

L'auteur décrit un dosage par complexométrie du fer(III), basé sur un nouveau procédé de détermination du point équivalent. On utilise comme indicateur l'orangé de xylénol qui forme un complexe violet-bleu stable. En ajoutant du fer(II) à la solution à titrer, la réaction de déplacement usuelle au point équivalent du titrage est remplacée par un processus d'oxydoréduction qui donne un point équivalent très net. Ce nouveau procédé rend possible un dosage du fer(III) précis et très sélectif. Seuls le bismuth, le thallium(III) et de grandes quantités de cuivre doivent être séparés avant le titrage.     

Über die Bromierung von 9-Vinylcarbazol

Zusammenfassung Bei der Bromierung von N-Vinylcarbazol wird unter verschiedenen Reaktionsbedingungen 3.6-Dibromcarbazol, 3.6-Dibrom-9-(1.2-dibromäthyl)carbazol, 3.6-Dibrom-9-(1-methoxy-2-bromäthyl)-carbazol und 3.6-Dibrom-9-(1-äthoxy-2-bromäthyl)-carbazol erhalten. Aus 9-Äthylcarbazol wurde 3.6-Dibrom-9-äthylcarbazol, aus 1.2-Bis(9-carbazyl)cyclobutan 1.2-Bis[9-(3.6-dibromcarbazyl)]cyclobutan und aus Poly-N-vinylcarbazol Poly-3.6-dibrom-9-vinylcarbazol dargestellt. Der Bromierungsmechanismus wird diskutiert.

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Bromination of N-vinylcarbazole

Bromination of N-vinylcarbazole under various conditions gives 3.6-dibromocarbazole, 3.6-dibromo-9-(1.2-dibromoethyl)-carbazole, 3.6-dibromo-9-(1-methoxy-2-bromoethyl)carbazole, and 3.6-dibromo-9-(1-ethoxy-2-bromoethyl)carbazole. 3.6-Dibromo-9-ethylcarbazole and 1.2-bis[9-(3.6-dibromocarbazyl)]-cyclobutane have been obtained from the corresponding carbazole derivatives, and poly-N-vinylcarbazole was brominated to poly-3.6-dibromo-9-vinylcarbazole. The bromination mechanism is discussed.

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An dieser Arbeit nahm ich als UNO-Stipendiat teil, wofür ich der UNO sehr zu Dank verpflichtet bin.     

Studies on the metabolism of the Δ9‐tetrahydrocannabinol precursor Δ9‐tetrahydrocannabinolic acid A (Δ9‐THCA‐A) in rat using LC‐MS/MS,LC‐QTOF MS and GC‐MS techniques

In Cannabis sativa, Δ9‐Tetrahydrocannabinolic acid‐A (Δ9‐THCA‐A) is the non‐psychoactive precursor of Δ9‐tetrahydrocannabinol (Δ9‐THC). In fresh plant material, about 90% of the total Δ9‐THC is available as Δ9‐THCA‐A. When heated (smoked or baked), Δ9‐THCA‐A is only partially converted to Δ9‐THC and therefore, Δ9‐THCA‐A can be detected in serum and urine of cannabis consumers. The aim of the presented study was to identify the metabolites of Δ9‐THCA‐A and to examine particularly whether oral intake of Δ9‐THCA‐A leads to in vivo formation of Δ9‐THC in a rat model. After oral application of pure Δ9‐THCA‐A to rats (15 mg/kg body mass), urine samples were collected and metabolites were isolated and identified by liquid chromatography‐mass spectrometry (LC‐MS), liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) and high resolution LC‐MS using time of flight‐mass spectrometry (TOF‐MS) for accurate mass measurement. For detection of Δ9‐THC and its metabolites, urine extracts were analyzed by gas chromatography‐mass spectrometry (GC‐MS). The identified metabolites show that Δ9‐THCA‐A undergoes a hydroxylation in position 11 to 11‐hydroxy‐Δ9‐tetrahydrocannabinolic acid‐A (11‐OH‐Δ9‐THCA‐A), which is further oxidized via the intermediate aldehyde 11‐oxo‐Δ9‐THCA‐A to 11‐nor‐9‐carboxy‐Δ9‐tetrahydrocannabinolic acid‐A (Δ9‐THCA‐A‐COOH). Glucuronides of the parent compound and both main metabolites were identified in the rat urine as well. Furthermore, Δ9‐THCA‐A undergoes hydroxylation in position 8 to 8‐alpha‐ and 8‐beta‐hydroxy‐Δ9‐tetrahydrocannabinolic acid‐A, respectively, (8α‐Hydroxy‐Δ9‐THCA‐A and 8β‐Hydroxy‐Δ9‐THCA‐A, respectively) followed by dehydration. Both monohydroxylated metabolites were further oxidized to their bishydroxylated forms. Several glucuronidation conjugates of these metabolites were identified. In vivo conversion of Δ9‐THCA‐A to Δ9‐THC was not observed. Copyright © 2009 John Wiley & Sons, Ltd.     

Diversity-oriented asymmetric synthesis of hapalosin: construction of three small C9/C4/C3-modified hapalosin analogue libraries

A flexible approach to the beta-hydroxy gamma-amino acid residue (fragment C) of hapalosin has been developed on the basis of the the regio- and diastereoselective Grignard reaction. The method allows the introduction of different side chains at the C9 of hapalosin. Asymmetric syntheses of hapalosin (1a), 9-homohapalosin (1b), 9-i-butyl-hapalosin (1c), 8-epi-hapalosin (epi-1a), and three small libraries diversified at C9 (3-member, 1L3), C9/ C4 (9-member, 1L9), or C9/C4/C3 (27-member, 1L27) have been produced using this method.     

The synthesis of 1H-benzimidazole derivatives containing a 9H-xanthene or 9H-thioxanthene ring

2-(9H-Xanthen-9-ylmethyl)-1H-benzimidazole ( 2a ) was prepared by condensing 9H-xanthene-9-acetic acid ( 1a ) with 1,2-benzenediamine. Similarly, 2-(9H-thioxanthen-9-ylmethyl)-1H-benzimidazole ( 2b ) and its S,S-dioxide ( 2d ) were obtained. Compound 2d was also prepared by oxidizing 2b with hydrogen peroxide in acetic acid. Heating of 9H-thioxanthene-9-acetic acid 10-oxide ( 1c ) with 1,2-benzenediamine gave 9-methylene-9H-thioxanthene ( 3 ). 2-(9H-Thioxanthen-9-ylmethyl)-1H-benzimidazole S-oxide ( 2c ) was obtained by oxidizing 2b with m-chloroperbenzoic acid in acetone.