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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.

[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.

Rhenium is technetium`s third row congener and exhibits many of the chemical properties that technetium displays. Theoretically, a Re-PhAT complex will be isostructural with the {sup 99m}Tc PhAT complexes that have been prepared for use as brain imaging agents. A series of neutral rhenium(V) oxo complexes was synthesized by the reaction of ReOBr{sub 4}{sup {minus}} with diamino-thiol-thioether ligands of the type (RSC(CH{sub 3}){sub 2})CH{sub 2}NH(o-C{sub 6}H{sub 4})NHCH{sub 2}C(CH{sub 3}){sub 2}SH. The complexes were characterized by IR, UV/visible, and {sup 1}H and {sup 13}C NMR spectroscopy and by fast-atom-bombardment mass spectroscopy. The single-crystal X-ray structure determination on two of the complexes, where R = CH{sub 2}CH{double_bond}CH{sub 2} and CH{sub 2}CH{sub 2}-CH{sub 3}, showed them to consist of a square pyramidal Re{sup V}ON{sub 2}S{sub 2} core. ReO[CH{sub 2}{double_bond}CHCH{sub 2}SC(CH{sub 3}){sub 2}CH{sub 2}N(o-C{sub 6}H{sub 4})NCH{sub 2}C(CH{sub 3}){sub 2}S], C{sub 17}H{sub 25}N{sub 2}OS{sub 2}Re, crystallizes in the monoclinic space group P2{sub 1}/a with {alpha} = 17.899(3) {angstrom}, b = 13.910(1) {angstrom}, c = 15.936(1) {angstrom}, {beta} = 104.70(1){degrees}, Z = 8, D{sub calc} = 1.813 g cm{sup {minus}3}, and {mu}(Cu K{alpha}) = 139.8 cm{sup {minus}1}. The propyl complex, C{sub 17}H{sub 27}N{sub 2}OS{sub 2}Re, crystallizes in the monoclinic space group P2{sub 1}/a with a =more » 18.076(1) {angstrom}, b = 13.920(1) {angstrom}, c = 15.994(1) {angstrom}, {beta} = 105.09(1){degrees}, Z = 8, D{sub calc} = 1.797 g cm{sup {minus}3}, and {mu}(Cu K{alpha}) = 138.0 cm{sup {minus}1}. The combination of the steric and electronic effects of the aromatic ring fused to the backbone of the N-C-C-N ligand and the S-substitution result in deprotonation of both amine nitrogens and coplanarity of the base of the square pyramidal complex.« less

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.

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.

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.

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.