E- or Z-Selective synthesis of 4-fluorovinyl-1,2,3-triazoles with fluorinated second-generation Julia-Kocienski reagents.

A highly modular approach to N-substituted 4-(1-fluorovinyl)triazoles is described. In situ desilylation and Cu-catalyzed ligation reaction of TMS-protected α-fluoropropargyl benzothiazole sulfone with aryl, alkyl, and metallocenyl azides furnished second-generation Julia-Kocienski reagents in good to excellent yields. Condensation reactions of these reagents with aldehydes can be tuned to yield E or Z-alkenes selectively. Under mild conditions with DBU as the base, reactions of aldehydes furnished E-alkenes as the major isomer. On the other hand, in condensation reactions with LHMDS as the base and in appropriate solvents, both aldehydes and ketones reacted to yield fluoroalkenes with Z-selectivity. Stereochemical assignment of E/Z olefins obtained in the reaction of a ketone with two Julia reagents was performed via X-ray crystallographic analysis and comparisons of NMR data. The method allows efficient and ready diversification of the N1-substituent and substituents at the double bond.

High-yielding aqueous 18F-labeling of peptides via Al18F chelation.

The coordination chemistry of a new pentadentate bifunctional chelator (BFC), NODA-MPAA 1, containing the 1,4,7-triazacyclononane-1,4-diacetate (NODA) motif with a methylphenylacetic acid (MPAA) backbone, and its ability to form stable Al(18)F chelates were investigated. The organofluoroaluminates were easily accessible from the reaction of 1 and AlF(3). X-ray diffraction studies revealed aluminum at the center of a slightly distorted octahedron, with fluorine occupying one of the axial positions. The tert-butyl protected prochelator 7, which can be synthesized in one step, is useful for coupling to biomolecules on solid phase or in solution. High yield (55-89%) aqueous (18)F-labeling was achieved in 10-15 min with a tumor-targeting peptide 4 covalently linked to 1. Defluorination was not observed for at least 4 h in human serum at 37 °C. These results demonstrate the facile application of Al(18)F chelation using BFC 1 as a versatile labeling method for radiofluorinating other heat-stable peptides for positron emission imaging.

Synthesis of an A'B' Precursor to Angelmicin B: Product Diversification in the Suárez Lactol Fragmentation.

We describe a synthetic strategy for the angelimicin family of anthraquinoid natural products that involves converting a central highly oxygenated decalin intermediate to the AB and A'B' subunits. Herein, we report the synthesis of the bicyclic A'B' subunit that complements our earlier route to the tricyclic AB framework. The differentiating tact in the two syntheses focused on controlling the Suárez radical fragmentation of lactol precursors by modulating the substrate's structural rigidity. A more flexible lactol gave the tricyclic AB framework, whereas a more rigid substrate led to the bicyclic A'B' precursor, presumably through divergent pathways from the radical produced in the initial fragmentation step. These results establish a versatile advanced synthetic precursor for the angelimicins, and on a more general note, illustrate strategies for applying the Suárez fragmentation to diverse and complex molecular frameworks.

Ternary Porphyrinato Hf(IV) and Zr(IV) - Polyoxometalate Complexes.

We report a facile, high yield synthesis and characterization of discrete, ternary porphyrin-metal-polyoxometalate (Por-M-POM) complexes where a group (IV) transition metal ion is bound both to the porphyrin core and to the lacunary site of a Keggin POM, PW(11)O(39) (-7). The remarkably robust complexes exploit the fact that Hf(IV) and Zr(IV) are 7-8 coordinate and reside outside the plane of the porphyrin macrocycle, thus enabling the simultaneous coordination to meso-tetraphenylporphyrin (TPP) or meso-tetra(4-pyridyl)porphyrin (TPyP) and to the defect site in the Keggin framework. The physical properties of the (TPP)Hf(PW(11)O(39))[TBA](5), (TPyP)Hf(PW(11)O(39))[TBA](5), and (TPP)Zr(PW(11)O(39))[TBA](5) complexes are similar because the metal ions have similar oxidation states, and coordination chemistry.This architecture couples the photonic properties of the porphyrin to the POM because the metal ion is incorporated into both frameworks. Thus the ternary complexes can serve as a basis for the characterization of Hf(IV) and Zr(IV) porphyrins bound to oxide surfaces via the group (IV) metal ions. The Hf(Por) and Zr(Por) bind strongly to TiO(2) nanoparticles and indium tin oxide (ITO) surfaces, but significantly less binds to crystalline SiO(2) or TiO(2) surfaces. Together, the strong binding of the metalloporphyrins to the POM, nanoparticles, and the ITO surfaces, and paucity of binding to crystalline surfaces, suggests that the 3-4 open coordination sites on the Hf(Por) and Zr(Por) are predominantly bound at surface defect sites.

Self-organization of a new fluorous porphyrin and C60 films on indium-tin-oxide electrode.

The highly fluorinated alkyl moieties of a new porphyrin drive the self-organization of thin films with C(60) on ITO electrodes.

On the two-component microwave-mediated reaction of isonitriles with carboxylic acids: regarding alleged formimidate carboxylate mixed anhydrides.

Microwave induced two-component coupling (2CC) reaction of carboxylic acids with isonitriles gives rise to various N-formylamides. The formimidate carboxylate mixed anhydride (FCMA) is proposed as the reactive intermediate, which undergoes 1,3-O-->N acyl transfer to give the observed product. The formation and survival of the labile FCMA system has been evaluated.

Synthesis of the AB subunit of angelmicin B through a tandem alkoxy radical fragmentation-etherification sequence.

The synthesis of the tricyclic enone 2, corresponding to the AB subunit of the novel tyrosine kinase inhibitor angelmicin B, is described. The strategy centers on an intramolecular Diels-Alder (IMDA) reaction on triene 4 to provide the complex decalin 3, which is elaborated to 2. Other key steps are the formation of the THF ring in 2 through a tandem alkoxy radical fragmentation-etherification on the lactol derived from 3, and the synthesis of 4 via a ring-closing ene-yne metathesis (RCEYM).

31P magic angle spinning NMR spectroscopy of paramagnetic rare-earth-substituted Keggin and Wells-Dawson solids.

Paramagnetic rare-earth elements have been examined as NMR structural probes in polyoxoanionic solids, which have a variety of applications as luminescent materials that are usually disordered and therefore intractable by traditional structural methods. Thirteen Keggin and Wells-Dawson polyoxotungstates containing substitutions with lanthanides of different effective magnetic moments have been examined by 31P magic angle spinning NMR spectroscopy. The electron-nuclear dipolar interaction dominating the spinning sideband envelopes is determined by the lanthanide's magnetic moment and was found to be a sensitive probe of the nature of the polyoxoanion, of the positional isomerism, and of the ion stoichiometry. Electron-nuclear dipolar anisotropies computed based on the point-dipole approximation are generally in good agreement with the experimental results. The choice of a specific lanthanide as a structural probe can be tailored to the desired distance range between the phosphorus atoms and the paramagnetic centers to be probed. This approach is expected to be particularly useful in the paramagnetic polyoxoanionic materials lacking long-range order.

Routes to new hafnium(IV) tetraaryl porphyrins and crystal structures of unusual phosphate-, sulfate-, and peroxide-bridged dimers.

New routes for the synthesis of mono tetraaryl porphyrinato hafnium(IV) complexes, Hf(IV)Por(L)(2), are reported, where the secondary ligands, L, are determined by the method of purification. These synthetic routes cater to the solubility of the macrocycles and provide access to Hf(IV) complexes of meso tetraaryl porphyrins bearing diverse functional groups such as phenyl, tolyl, pyridyl, pentafluorophenyl, and carboxyphenyl. The latter three derivatives significantly expand the repertoire of hafnium porphyrinates. One route refluxes the porphyrin with HfCl(4) in 1-chloronaphthalene or in a mixed solvent of 1-chloronaphthalene and o-cresol. A second, solventless method is also reported wherein the porphyrin is mixed with Hf(cp)(2)Cl(2) and heated to give the metalated porphyrin in good yields. Simultaneous purification and formation of stable porphyrinato hafnium(IV) diacetate complexes, Hf(Por)OAc(2), is accomplished by elution over silica gel using 3-5% acetic acid in the eluent. Exchange of the acetate ligands for other oxo-bearing ligands can be nearly quantitative, such as p-aminobenzoate (PABA), pentanoate (pent), or octanoate (oct). Notably, we find that two to three of a variety of small multitopic dianions such as peroxo (O(2)(-2)), SO(4)(-2), and HPO(4)(-2) serve to bridge between two Hf(Por) moieties to form stable dimers. The crystal structures of this library of Hf(Por) complexes are reported, and we note that careful analysis of crystallography data reveals (Por)Hf(micro-eta(2)-O(2))(2)Hf(Por) rather than four bridging oxo or hydroxy ions.

New Drimane Sesquiterpenoids from Tidestromia oblongifolia.

From an acetone extract of the aerial parts of Tidestromia oblongifolia (Amaranthaceae), a new drimane sesquiterpenoid bearing an 11,12,13-trihydroxydrimene skeleton (1) as well as the 11,12 acetonide of 1 were isolated. Three known stigmastane triterpenoids were also isolated. Structures were elucidated with the aid of 1D and 2D NMR spectroscopic techniques. The absolute configuration of 1 was confirmed by single-crystal x-ray crystallography. This is the first report on phytochemical constituents from any plant of the genus Tidestromia and is the first report of the occurrence of drimanes in the Amaranthaceae.

MO tripeptide diastereomers (M=99/99mTc, Re): models to identify the structure of 99mTc peptide targeted radiopharmaceuticals.

Biologically active molecules, such as many peptides, serve as targeting vectors for radiopharmaceuticals based on 99mTc. Tripeptides can be suitable chelates and are easily and conveniently synthesized and linked to peptide targeting vectors through solid-phase peptide synthesis and form stable TcVO complexes. Upon complexation with [TcO]3+, two products form; these are syn and anti diastereomers, and they often have different biological behavior. This is the case with the approved radiopharmaceutical [99mTcO]depreotide ([99mTcO]P829, NeoTect) that is used to image lung cancer. [99mTcO]depreotide indeed exhibits two product peaks in its HPLC profile, but assignment of the product peaks to the diastereomers has proven to be difficult because the metal peptide complex is difficult to crystallize for structural analysis. In this study, we isolated diastereomers of [99TcO] and [ReO] complexes of several tripeptide ligands that model the metal chelator region of [99mTcO]depreotide. Using X-ray crystallography, we observed that the early eluting peak (A) corresponds to the anti diastereomer, where the Tc=O group is on the opposite side of the plane formed by the ligand backbone relative to the pendant groups of the tripeptide ligand, and the later eluting peak (B) corresponds to the syn diastereomer, where the Tc=O group is on the same side of the plane as the residues of the tripeptide. 1H NMR and circular dichroism (CD) spectroscopy report on the metal environment and prove to be diagnostic for syn or anti diastereomers, and we identified characteristic features from these techniques that can be used to assign the diastereomer profile in 99mTc peptide radiopharmaceuticals like [99mTcO]depreotide and in 188Re peptide radiotherapeutic agents. Crystallography, potentiometric titration, and NMR results presented insights into the chemistry occurring under physiological conditions. The tripeptide complexes where lysine is the second amino acid crystallized in a deprotonated metallo-amide form, possessing a short N1-M bond. The pKa measurements of the N1 amine (pKa approximately 5.6) suggested that this amine is rendered more acidic by both metal complexation and the presence of the lysine residue. Furthermore, peptide chelators incorporating a lysine (like the chelator of [TcO]depreotide) likely exist in the deprotonated form in vivo, comprising a neutral metal center. Deprotonation possibly mediates the interconversion process between the syn and anti diastereomers. The N1 amine group on non-lysine-containing metallopeptides is not as acidic (pKa approximately 6.8) and does not deprotonate and crystallize as do the metallo-amide species. Three of the tripeptide ligands (FGC, FSC, and FKC) were radiolabeled with 99mTc, and the individual syn and anti isomers were isolated for biodistribution studies in normal female nude mice. The main organs of uptake were the liver, intestines, and kidneys, with the FGC compounds exhibiting the highest liver uptake. In comparing the diastereomers, the syn compounds had substantially higher organ uptake and slower blood clearance than the anti compounds.

Cyclic peptoids.

Foldamers are an intriguing family of biomimetic oligomers that exhibit a propensity to adopt stable secondary structures. N-Substituted glycine oligomers, or "peptoids", are a prototypical example of these foldamer systems and are known to form a helix resembling that of polyproline type I. Ongoing studies seek to improve the stability of peptoid folding and to discover new secondary structure motifs. Here, we report that peptoids undergo highly efficient head-to-tail macrocyclization reactions. A diverse array of peptoid sequences from pentamers to 20mers were converted to macrocyclic products within 5 min at room temperature. The introduction of the covalent constraint enhances conformational ordering, allowing for the crystallization of a cyclic peptoid hexamer and octamer. We present the first X-ray crystallographic structures of peptoid hetero-oligomers, revealing that peptoid macrocycles can form a reverse-turn conformation.

Efficient microwave-assisted synthesis of amine-substituted tetrakis(pentafluorophenyl)porphyrin.

We report an efficient and rapid means for the synthesis of tetrakis(pentafluorophenyl)porphyrin (TPPF(20)) derivatives by microwave irradiation in an environmentally acceptable solvent. The selective displacement of the para-fluorine groups in TPPF(20) by primary amines occurs in yields between 70 and 95%. This method demonstrates that TPPF(20) is an ideal platform for the rapid formation of porphyrin conjugates for therapeutic, catalytic, and other applications. [reaction: see text]

Influence of steric and electronic properties of the defect site, lanthanide ionic radii, and solution conditions on the composition of lanthanide(III) alpha1-P2W17O6110- polyoxometalates.

This study identifies the principles that govern the formation and stability of Ln complexes of the (alpha(1)-P(2)W(17)O(61))(10-) isomer. The conditional stability constants for the stepwise formation equilibria, K(1cond) and K(2cond), determined by (31)P NMR spectroscopy, show that the high log K(1cond)/log K(2cond) ratio predicts the stabilization of the 1:1 Ln/ (alpha(1)-P(2)W(17)O(61))(10-) species. The value of log K(1cond) increases as the Ln series is traversed, consistent with the high charge/size requirement of the basic alpha(1) defect site. The conditional stability constants, K(2), are very low and are highly dependent on the countercations in the buffer. The source of the instability is understood from the crystal structures of the early-mid lanthanide analogues, where the close contact of the (alpha(1)-P(2)W(17)O(61))(10-) units result in severe steric encumbrance. The electronic properties of the alpha(1) defect along with the lanthanide ionic radii and countercation composition are important parameters that need to be considered for a rational synthesis of lanthanide polyoxometalates.

The use of squaric acid as a scaffold for cofacial phenyl rings.

[structure: see text] To examine the possibility of using squaric acid as a scaffold for organizing phenyl rings in a cofacial orientation, we undertook an investigation of the conformational preferences of secondary and tertiary N-phenylsquaramides. In secondary squaramides, the extended ZZ conformation is preferred, while in the N-methyl derivative, the folded EE conformation with cofacial phenyl rings is preferred. This conformational switch is likely driven by a combination of steric and electronic factors.

Aqueous speciation studies of europium(III) phosphotungstate.

The incorporation of lanthanide ions into polyoxometalates may be a unique approach to generate new luminescent, magnetic, and catalytic functional materials. To realize these new applications of lanthanide polyoxometalates, it is imperative to understand the solution speciation chemistry and its impact on solid-state materials. In this study we find that the aqueous speciation of europium(III) and the trivacant polyoxometalate, PW9O34 9-, is a function of pH, countercation, and stoichiometry. For example, at low pH, the lacunary (PW11O39)7- predominates and the 1:1 Eu(PW11O39)4-, 2, forms. As the pH is increased, the 1:2 complex, Eu(PW11O39)2 11- species, 3, and (NH4)22[(Eu2PW10O38)4(W3O8(H2O)2(OH)4].44H2O, a Eu8 hydroxo/oxo cluster, 1, form. Countercations modulate this effect; large countercations, such as K+ and Cs+, promote the formation of species 3 and 1. Addition of Al(III) as a counterion results in low pH and formation of [Eu(H2O)3(alpha-2-P2W17O61)]2, 4, with Al(III) counterions bound to terminal W-O bonds. The four species observed in these speciation studies have been isolated, crystallized, and characterized by X-ray crystallography, solution multinuclear NMR spectroscopy, and other appropriate tech-niques. These species are 1, (NH4)22[(Eu2PW10O38)4(W3O8(H2O)2(OH)4].44H2O (P; a=20.2000(0), b=22.6951(6), c=25.3200(7) A; alpha=65.6760(10), beta=88.5240(10), gamma=86.0369(10) degrees; V=10550.0(5) A3; Z=2), 2, Al(H3O)[Eu(H2O)2PW11O34].20H2O (P, a=11.4280(23), b=11.5930(23), c=19.754(4) A; alpha=103.66(3), beta=95.29(3), gamma=102.31(3) degrees; V =2456.4(9) A3; Z=2), 3, Cs11Eu(PW11O34)2.28H2O (P; a=12.8663(14), b=19.8235(22), c=21.7060(23) A; alpha=114.57(0), beta=91.86(0), gamma=102.91(0) degrees ; V=4858.3(9) A3; Z=2), 4, Al2(H3O)8[Eu(H2O)3(alpha-2-P2W17O61)]2.29H2O (P; a=12.649(6), b=16.230(8), c=21.518(9) A; alpha=111.223(16), beta=94.182(18), gamma=107.581(17) degrees ; V=3842(3) A3; Z=1).

Stereoselective synthesis of P-chiral phosphorus compounds from N-tert-butoxycarbonyl amino acids.

Reaction of the N-t-Boc amino acids alanine and valine with PhPCl(2) gives the P-chiral trans-1,3,2-oxazaphospholidinones exclusively. Variable-temperature NMR and examination of the glycine derivative shows that the isomers observed are due to t-Boc rotation.

51V magic angle spinning NMR spectroscopy of Keggin anions [PVnW12-nO40](3+n)-: effect of countercation and vanadium substitution on fine structure constants.

Vanadium environments in Keggin oxopolytungstates were characterized by (51)V solid-state MAS NMR spectroscopy. (C(4)H(9))(4)N(+)-, K(+)-, Cs(+)-, as well as mixed Na(+)/Cs(+)- salts of the mono-, di-, and trivanadium substituted oxotungstates, [VW(11)O(40)](4-), [V(2)W(10)O(40)](5-), and [V(3)W(9)O(40)](6-), have been prepared as microcrystalline and crystalline solids. Solid-state NMR spectra report on the local environment of the vanadium site in these Keggin ions via their anisotropic quadrupolar and chemical-shielding interactions. These (51)V fine structure constants in the solid state are determined by the number of vanadium atoms present in the oxoanion core. Surprisingly, the quadrupolar anisotropy tensors do not depend to any significant extent on the nature of the countercations. On the other hand, the chemical-shielding anisotropy tensors, as well as the isotropic chemical shifts, display large variations as a function of the cationic environment. This information can be used as a probe of the local cationic environment in the vanadium-substituted Keggin solids.

Why are silyl ethers conformationally different from alkyl ethers? Chair-chair conformational equilibria in silyloxycyclohexanes and their dependence on the substituents on silicon. The wider roles of eclipsing, of 1,3-repulsive steric interactions, and of attractive steric interactions.

An NMR study of the diaxial/diequatorial chair equilibrium in a range of silylated derivatives of trans-1,4- and trans-1,2-dihydroxycyclohexane is reported and discussed with a view to explaining unusually large populations of chair conformations with axial substituents, noted previously for some monosilyloxycyclohexanes and in some silylated sugars. X-ray diffraction studies of three bis-triphenylsilyloxycyclohexanes are reported and show both axial and equatorial silyloxy groups with the exocyclic bonds eclipsed. Eclipsing is also suggested by molecular mechanics (MM3) calculations on such derivatives. Both axial and equatorial tertiary silyl groups have 1,3-repulsive interactions with whatever substituents or hydrogen atoms are at the two adjacent equatorial positions, and these are relieved by rotation toward the eclipsed conformation of the exocyclic C-O bond. The three substituents on silicon interact attractively with the nine atoms at the 3, 4, and 5-positions of the cyclohexane ring and calculations suggest that these stabilizing interactions are significantly greater in the axial than in the equatorial conformation. An equatorial C-OSiR(3) bond with one or two equatorial neighbors has a restricted potential energy well that becomes much broader when the bond is axial without any equatorial neighbors in the alternative chair. Adjacent silyl groups in the 1,2-disubstituted series interact in a stabilizing way overall in all conformations, this being particularly marked in the diaxial conformation of the more complex ethers. These factors lead to unusually large axial populations.

51V magic angle spinning NMR spectroscopy of six-coordinate Lindqvist oxoanions: a sensitive probe for the electronic environment in vanadium-containing polyoxometalates. Counterions dictate the 51V fine structure constants in polyoxometalate solids.

Geometric and electronic environments of vanadium have been addressed by (51)V magic angle spinning NMR spectroscopy of six-coordinated polyoxometalate solids. (C(4)H(9))(4)N(+) and mixed Na(+)/Cs(+) salts of the Lindqvist-type mono- and divanadium-substituted oxotungstates, [VW(5)O(19)](3-) and [V(2)W(4)O(19)](4-), have been prepared as microcrystalline and crystalline solids. The solid-state NMR spectra reflect the details of the local environment of the vanadium site in these hexametalate solids via the anisotropic quadrupolar and chemical shielding interactions. Remarkably, these (51)V fine structure constants in the solid state are dictated by the nature and geometry of the countercations. Electrostatic calculations of the electric field gradients at the vanadium atoms have been performed. Experimental trends are well reproduced with the simple electrostatic model, and explain the sensitivity of the anisotropic NMR parameters to the changes in the cationic environment at the vanadium site.