Biomedical subjects
Publications and source records attributed to Martin Nieger.
The title compound, C(18)H(35)NO(4), is a new bioactive amphiphilic lipid with a cis-substituted 1,3-oxazolidin-2-one head group. In the crystal structure, the molecules form intercalating bilayers in which the oxazolidinone head groups are joined together by hydrogen bonds into chains.
The synthesis of a new tetralactam macrocycle and the simultaneous formation of catenanes and larger octalactam macrocycles is reported. These species bear 2,2'-biquinoline moieties suitably positioned to bind a metal center at the outer periphery of the macrocycles. (1)H NMR chemical shifts permit the unambiguous distinction of transoid and cisoid conformations of the biquinoline moiety, thereby allowing an unequivocal identification of the catenane and octalactam structures, despite the fact that both have the same elemental composition and bear identical structural subunits. With the aid of an anion template effect, rotaxanes can be prepared from the smaller tetralactam macrocycle. These reveal significantly altered requirements in terms of the stopper size as compared to previously reported tetralactam wheels. Several copper(I)-mediated dimers and a (bpy)(2)Ru(II) complex (bpy=2,2'-bipyridine) have been synthesized from the tetralactam macrocycle and the rotaxanes. The anion binding abilities of the tetralactam macrocycle and its (bpy)(2)Ru(II) complex in DMSO have been compared by (1)H NMR titration experiments, which revealed significantly enhanced binding by the metal complex. Mass spectrometry has been used to study the potential formation of larger assemblies of copper(I) and the catenane built-up from two tetralactam macrocycles. Indeed, a 2:2 complex was identified. In contrast, the octalactam macrocycle of the same elemental composition yields only 1:1 complexes, with the Cu(I) ion connecting its two biquinoline moieties in the center of a figure-eight-shaped molecule. Molecular modeling studies support the structural assignments made.
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1-Triphenylphosphoniobenzo[c]phospholide 1 reacts with [M(CO)(5)Br] (M = Mn, Re) and [Mn(CO)(3)(naphthalene)][BF(4)] to give complexes cis-[M(CO)(4)(1)Br] (5 a,b) and [Mn(CO)(3)(1)][BF(4)] (6 a[BF(4)]), respectively, featuring eta(1)(P)- and eta(5)(pi)-coordination of the phosphole ring. The corresponding reactions with [M(2)(CO)(10)] proceed with conservation of the metal-metal bond and yield, depending on the reaction temperature, dinuclear complexes [M(2)(CO)(8)(1)] (M=Mn, 7 a) or [M(2)(CO)(6)(1)(2)] (M=Mn, Re, 8 a,b) with mu(2)-bridging eta(1)(P):eta(2)(Pdbond;C) coordination of the phosphole moiety. All complexes formed were characterized by spectroscopic data; 5 b, 6 a[BF(4)], and 8 a,b were characterized by X-ray diffraction studies as well. The structural and (31)P NMR data of the dinuclear manganese complex 8 a suggest that the interaction between the metal atoms and the eta(2)-bound Pdbond;C double bond moieties is dominated by the L-->M charge-transfer contribution; this hints at a very low back-donation ability of the central M(2)(CO)(6) fragment. Investigation of the reactions of the Mn complexes 6 a and 8 a with Mg or ferrocenium hexafluorophosphate ([Fc][PF(6)]), respectively, revealed that the chemically reversible mutual interconversion between both species was feasible. Likewise, oxidation of the rhenium complex 8 b with [Fc][PF(6)] gave spectroscopic evidence for the formation of a Re analogue of 6 a. Electrochemical studies suggested that the oxidation 8 a-->2 6 a involves two consecutive single-electron-transfer steps, the first of which is electrochemically reversible and produces a metastable radical cation that is detectable by ESR spectroscopy. The mutual interconversion between 6 a and 8 a represents the first case of a reversible coordination isomerization of a phosphaarene that is triggered by a redox process and might stimulate further studies directed at the use of dinuclear phosphaarene complexes in redox-catalysis.
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For the first time, knot molecules (of the amide type) are synthesized, which bear one to three dendritic units of various generations at their periphery. They were obtained through two different routes: i) attachment of dendritic wedges to new mono-, di- and trihydroxy functionalized dodecaamide knots that have been obtained by selective debenzylation of oligobenzyloxy substituted knots, or ii) cyclization of already dendron substituted pyridine-2,6-dicarbonyl dichlorides with an "extended diamine" to directly yield the "tri-dendroknots". The derivatization of knot molecules by functional substituents and even large dendritic units is an important advance in the synthesis and property variation of molecular knots. This holds true in particular for substitution of the pyridine units of the knots, whereas the isophthalic acid units seem not to tolerate larger substitutents, as reflected in lower knot yields. These syntheses also demonstrate knots to be accessible indirectly by substitution of the corresponding mono-, di- and tri-functionalized knot skeleton. An advantage of dendritic "decoration" is the control of solubility and chromatographic behaviour of the molecular knots (knotanes). Suggestions are made about the threading mechanism by supramolecular template effects leading to the formation of amide-based molecular knots. The topological chirality of the new "dendroknots" is shown by efficient enantioseparations (separation factor alpha between 1.22 and 1.48). For this purpose (commercially unavailable) chiral column material of the Chiralpak type was used, in which the chiral component is covalently bonded to the silica gel support. The racemate splittings provide additional evidence for the knotted structure, as all other conceivable isomers such as macromonocyclic or catenated dodecaamides would not be chiral. The pure enantiomers obtained exhibit pronounced Cotton effects in their circular dichroism spectra. By comparison with the unsubstituted knot, the absolute configuration (Lambda, Delta) of all new knots is derived.
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The first stable phosphaarene pi-complex of copper displays unusual 31P NMR data that suggest a novel interpretation of 31P coordination shifts in pi-complexes of phosphorus containing multiple bonds.
Reaction of the 1,3-diphosphacyclobutane-2,4-diyl-2-ide 1 with chromium or tungsten hexacarbonyl afforded the anionic complexes [cyclo-[P(Mes*)-C(SiMe(3))-P(Mes*)-C(O)-C[M(CO)(5)]]](-) (3 a,b: M=Cr, W) by the formal insertion of CO into the four membered ring. Computational analysis suggests that this reaction proceeds via two intermediates that can be formulated as a cyclic metal acyl and an acyclic ketenyl complex. The anionic complexes 3 a,b further reacted with electrophiles to afford the neutral complexes [cyclo-(P(Mes*)-C(SiMe(3))-P(Mes*)-C(OR)-C[M(CO)(5)])] (4 a,b: M=Cr, W, R=Me; 5, 6: M=Cr, R=SiMe(3), H). All products were characterized by standard spectroscopic (NMR and MS) techniques, and 4 a,b further by extensive one- and two-dimensional multinuclear ((1)H, (13)C, (31)P, (183)W) NMR studies. From these investigations, an unequivocal assignment of chemical shifts and coupling constants was derived, confirming unusually large shielding for the formal carbenic carbon atoms which exceed even those in complexes of imidazoyl carbenes. Single-crystal X-ray diffraction analyses of 3 a, 4 a,b, and 5 revealed that all of these compounds contain planar P(2)C(3) rings. The phosphorus atoms are slightly pyramidal, and the carbon-metal distances (C-Cr 218 pm, C-W 230 pm) suggest low bond orders. Comparison of the structural parameters of 3 a with those of the O-substitution products 4 a, 5 revealed substantial changes in endocyclic P-C bond lengths and the degree of pyramidal character of bonding at the phosphorus atoms. In line with the spectroscopic and computational results, these effects were interpreted in terms of a considerable reorganization of pi electrons in the ring, which induces a substantial degree of aromatic character in the neutral complexes 4-6.
Bimetallic, pentel-bridged complexes of the type [(dmap)Me2M-E(SiMe3)2-M'(CO)n] (M=Al, Ga; E=P, As, Sb; M'=Cr, Fe, Ni; DMAP=4-(dimethylamino)pyridine) are formed by reactions of DMAP-coordinated monomeric Group 13/15 compounds [(dmap)Me2M-E(SiMe3)2] with the transition metal complexes [(Me3N)Cr(CO)5], [Fe3(CO)12], and [Ni(CO)4]. For the first time, this reaction offers a general pathway to compounds containing a Group 13 metal and a transition metal bridged by a pentel atom. Complexes prepared in this way were characterized by IR and multinuclear NMR spectroscopy and by single-crystal X-ray structure analysis. Their electronic and structural properties are discussed in detail. The Group 13/15 ligands are very weak acceptors, which is likely to be due to the electropositive Group 13 metal, and the complexes feature comparatively long pentel-transition metal bonds. In addition, the synthesis and structural characterization of the parent DMAP-coordinated gallanes [(dmap)Me2Ga-E(SiMe3)2] (E=P, As) are reported.
A new synthesis of ent-senepoxide and iso-crotepoxide starting from microbially produced(+)-trans-2,3-dihydroxy-2,3-dihydrobenzoic acid via regio- and stereoselective epoxidation is described.
LE 300 represents a structurally novel type of antagonist acting preferentially at the dopamine D1/D5 receptors and the serotonin 5-HT2A receptor. The compound consists of a 10-membered central azecine ring fused to indole on one and to benzene on the other side. To estimate the importance of the indole moiety in this highly active benz-indolo-azepine, the indole has to be removed and the "de-indolised" analog reinvestigated pharmacologically. Accordingly, we synthesized 3-benzazecines and in addition some homologuous 3-benzazonines. Methoxylated beta-phenylethylamines were treated with ethyl omega-bromo-butanoates and -pentanoates, respectively, to give the corresponding lactams which were cyclized (POCl3) and reduced (NaBH4), yielding the cis-annelated (X-ray) benzindolizines and -quinolizines. The 10- and 9-membered rings were obtained by cleavage of the central C-N bond, which was performed in the following two ways: Quarternisaion with methyl iodide and cleavage with sodium in liquid ammonia gave the NCH3 derivatives, reaction with benzyloxycarbonyl chloride/NaBH4 followed by catalytic debenzylation yielded a corresponding NH compound. Functional experiments on rat artery segments precontracted with ketanserin and radioligand binding experiments using human cloned dopamine receptor subtypes were conducted with all of the benzazecine and benzazonine derivatives. In contrast to the benz-indolo-compound LE 300 they did not show any significant affinity towards the D1, D2, D4, and D5 receptors and only moderate antagonistic activity at the 5-HT2A receptor. It can be concluded from our study that an indole moiety or at least another second aromatic system at the central azecine ring is part of the pharmacophore and thus essential for high biological activity.
Bis(triphenylphosphonio)isophosphindolide triflate (1[CF(3)SO(3)]) reacted with HgCl(2) and H(2)O or MeOH to give a phosphinito complex which was converted with excess HgCl(2) into the dimercury complex 5. In contrast, methanolysis of 1[X] (X = CF(3)SO(3), Br) in the presence of Hg(OAc)(2) afforded the phosphonium cation 9. A mercury complex 8 was isolated for X = Br as a reaction intermediate. Salts of a macrocyclic cation with a constitution similar to that of 9 were obtained by reaction of 1[CF(3)SO(3)] with Hg(OAc)(2) and triethylene glycol. The products were characterised by (1)H, (13)C, and (31)P NMR spectroscopy; in addition, (199)Hg NMR data of some complexes were obtained from 2D (31)P,(199)Hg shift correlations. Complexes 5 (space group P2(1)2(1)2(1), Z = 4, a = 12.449(2) Å, b = 17.583(3) Å, c = 23.111(3) Å, V = 5058.8(14) Å(3), 8917 reflections refined to R(w2) = 0.103) and 8 (space group C2/c, Z = 8, a = 20.028(2) Å, b = 15.513(2) Å, c = 30.247(8) Å, beta = 91.91(1) degrees, V = 9392(3) Å(3), 7955 reflections refined to R(w2) = 0.177) were further characterized by single crystal X-ray diffractommetry. Compound 8 is the first example of a monomeric complex of the type LHgX(2) (L = phosphine donor, X = halogen); formation of a halide bridged dimer is presumably prevented by the extraordinarily sterically demanding ligand. A reaction mechanism for the formation of 5 and 8 is proposed which involves the formation of mercury complexes of 1 as the initial step.
The structure of P,P-bis(diisopropylamino)-4-phenyl-1,3,2lambda(5)-diazaphosphete, 1a, has been determined by a single-crystal X-ray diffraction study (C(19)H(33)N(4)P, monoclinic system, space group P2(1), a = 9.482(1) Å, b = 11.374(3) Å, c = 9.668(2) Å, beta = 97.16(1) degrees, Z = 2). According to quantum chemical calculations at an RHF level of optimization utilizing the 6-31g(d,p) basis set, 1a has a zwitterionic structure with the negative charge delocalized on the NCN allylic fragment and the positive charge localized at the phosphorus. Heterocycle 1a reacts with water and benzaldehyde affording N-phosphoranylbenzamidine 3 (95% yield) and the expected aza-Wittig adduct 4 (85% yield), respectively. Addition of 1 equiv of methyl trifluoromethanesulfonate and of 2 equiv of BH(3).THF to 1a affords cyclic phosphonium salt 5 (94% yield) and the bis(borane) adduct 6a (90% yield), respectively. Dimethyl acetylenedicarboxylate slowly reacts with 1a giving rise to 1,3,4lambda(5)-diazaphosphinine, 9, in 70% yield. The X-ray crystal structures of products 2,3, and 6a are reported (2: C(26)H(38)N(5)P, monoclinic system, space group C2/c, a = 16.337(8) Å, b = 19.810(2) Å, c = 8.800(2) Å, beta = 117.68(2) degrees, Z = 4. 3: C(19)H(35)N(4)OP, orthorhombic system, space group P2(1)2(1)2(1), a = 9.090(1) Å, b = 12.955(2) Å, c = 17.860(3) Å, Z = 4. 6a: C(19)H(39)B(2)N(4)P, orthorhombic system, space group P2(1)2(1)2(1), a = 10.340(1) Å, b = 13.247(1) Å, c = 16.996(1) Å, Z = 4).