1-Hydroxymethyl-4-phenylsulfonybutadiene, a versatile building block for the synthesis of 2,3,4-trisusbtituted tetrahydrothiophenes

A method to synthesize chiral 2,3,4-trisusbtituted tetrahydrothiophenes in both enantiomerically pure forms starting from 1-hydroxymethyl-4-phenylsulfonylbutadiene is described.     

The normalizer of the level (2,2)-Heisenberg Group

The level (2, 2)-Heisenberg GroupG(2, 2) as first introduced by Mumford in [Mu] is a subgroup inSL(4,ℂ) of order 32. LetN be the normalizer ofG(2, 2) inSL(4,ℂ). This note describes explicitely the two natural isomorphisms fromN/G(2, 2) to the symmetric group of 6 elements. These identifications clarify the computations in the classical treatises as for example in the theory of Kummer surfaces in [Hu] and the theory of the quadric line complex as in [Je] and will be used in [Nie] to describe the moduli space for abelian surfaces with a level (2, 6)-structure.     

Nucleophilic aromatic substitution of hydrogen through lithiated phosphine borane complexes and N-phosphorylphosphazenes

Organophosphorus compounds containing nitroaryl and cyanoaryl groups have been prepared in good yield through nucleophilic aromatic substitution of hydrogen using α-lithiated phosphazenes and phosphine borane complexes as nucleophiles. In all cases, nearly exclusive replacement of the hydrogen in the para position with respect to the activating group has been observed.     

Highly enantioselective ruthenium-catalyzed reduction of ketones employing readily available Peptide ligands

Highly efficient and selective catalysts for the asymmetric reduction of aryl alkyl ketones under hydrogen-transfer conditions (2-propanol) were obtained by combining a novel class of pseudo-dipeptide ligands with [[RuCl(2)(p-cymene)](2)]. A library of 36 dipeptide-like ligands was prepared from N-Boc-protected alpha-amino acids and the enantiomers of 2-amino-1-phenylethanol and 1-amino-2-propanol. The catalyst library was evaluated with the reduction of acetophenone and excellent enantioselectivity of 1-phenylethanol was obtained with several of the novel catalysts. A ligand based on the combination of N-Boc-L-alanine and (S)-1-amino-2-propanol (ligand A-(S)-4) was found to be particular effective. When the situ formed ruthenium complex of this ligand was employed as the catalyst in the hydrogen-transfer reaction of various aryl alkyl ketones, the corresponding alcohol products were achieved in excellent enantioselectivity (up to 98 % ee).     

Similar molecular constitutions but different conformations and different supramolecular assemblies in two related fused tetracyclic benzo[b]pyrimido[5,4‐f]azepine derivatives

A simple and effective two‐step approach to tricyclic pyrimidine‐fused benzazepines has been adapted to give the tetracyclic analogues. In (RS)‐8‐chloro‐6‐methyl‐1,2,6,7‐tetrahydropyrimido[5′,4′:6,7]azepino[3,2,1‐hi]indole, C₁₅H₁₄ClN₃, (I), the five‐membered ring adopts an envelope conformation, as does the reduced pyridine ring in (RS)‐9‐chloro‐7‐methyl‐2,3,7,8‐tetrahydro‐1H‐pyrimido[5′,4′:6,7]azepino[3,2,1‐ij]quinoline, C₁₆H₁₆ClN₃, (II). However, the seven‐membered rings in (I) and (II) adopt very different conformations, with the result that the methyl substituent occupies a quasi‐axial site in (I) but a quasi‐equatorial site in (II). The molecules of (I) are linked by C—H...N hydrogen bonds to form C(5) chains and inversion‐related pairs of chains are linked by a π–π stacking interaction. A combination of a C—H...π hydrogen bond and two C—Cl...π interactions links the molecules of (II) into complex sheets. Comparisons are made with some similar fused heterocyclic compounds.     

Surface Tension of Liquid Organic Acids: An Artificial Neural Network Model

An artificial neural network model is proposed for the surface tension of liquid organic fatty acids covering a wide temperature range. A set of 2051 data collected for 98 acids (including carboxylic, aliphatic, and polyfunctional) was considered for the training, testing, and prediction of the resulting network model. Different architectures were explored, with the final choice giving the best results, in which the input layer has the reduced temperature (temperature divided by the critical point temperature), boiling temperature, and acentric factor as an independent variable, a 41-neuron hidden layer, and an output layer consisting of one neuron. The overall absolute percentage deviation is 1.33%, and the maximum percentage deviation is 14.53%. These results constitute a major improvement over the accuracy obtained using corresponding-states correlations from the literature.     

Synthesis of an ent-halimanolide from ent-halimic acid

An efficient synthesis of ent-halimanolide 2 (15,16-epoxy-12-oxo-ent-halima- 5(10),13(16),14-trien-18,2beta-olide), from ent-halimic acid has been achieved, corroborating the structure of the natural compound and establishing its absolute configuration.     

Ternary Polymer Solutions with Hydrogen Bonds, 2

Experimental ternary phase diagrams for ternary systems CHL/PS‐MAA/PVPy with diverse MAA contents have been determined by GPC. The presence of MAA in the copolymers gives rise to specific interactions, by hydrogen bond formation between both polymeric components, so strong that the isotherm for the system with the highest MAA content so far studied, CHL/PS‐MAA(8%)/PVPy, is representative of a complex coacervation situation. By applying the theoretical background deduced by coupling the Flory‐Huggins lattice model to the AET developed for ternary polymeric systems SPP with specific intermolecular interactions (via hydrogen bonds), free energy surfaces for the CHL/PS‐MAA/PVPy systems are constructed. From these plots theoretical ternary phase diagrams are deduced and a fair agreement with those obtained experimentally is observed.

     

A High Separation Factor for 165Er from Ho for Targeted Radionuclide Therapy

Background: Radionuclides emitting Auger electrons (AEs) with low (0.02–50 keV) energy, short (0.0007–40 µm) range, and high (1–10 keV/µm) linear energy transfer may have an important role in the targeted radionuclide therapy of metastatic and disseminated disease. Erbium-165 is a pure AE-emitting radionuclide that is chemically matched to clinical therapeutic radionuclide ¹⁷⁷Lu, making it a useful tool for fundamental studies on the biological effects of AEs. This work develops new biomedical cyclotron irradiation and radiochemical isolation methods to produce ¹⁶⁵Er suitable for targeted radionuclide therapeutic studies and characterizes a new such agent targeting prostate-specific membrane antigen. Methods: Biomedical cyclotrons proton-irradiated spot-welded Ho_(m) targets to produce ¹⁶⁵Er, which was isolated via cation exchange chromatography (AG 50W-X8, 200–400 mesh, 20 mL) using alpha-hydroxyisobutyrate (70 mM, pH 4.7) followed by LN2 (20–50 µm, 1.3 mL) and bDGA (50–100 µm, 0.2 mL) extraction chromatography. The purified ¹⁶⁵Er was radiolabeled with standard radiometal chelators and used to produce and characterize a new AE-emitting radiopharmaceutical, [¹⁶⁵Er]PSMA-617. Results: Irradiation of 80–180 mg ^natHo targets with 40 µA of 11–12.5 MeV protons produced ¹⁶⁵Er at 20–30 MBq·µA⁻¹·h⁻¹. The 4.9 ± 0.7 h radiochemical isolation yielded ¹⁶⁵Er in 0.01 M HCl (400 µL) with decay-corrected (DC) yield of 64 ± 2% and a Ho/¹⁶⁵Er separation factor of (2.8 ± 1.1) · 10⁵. Radiolabeling experiments synthesized [¹⁶⁵Er]PSMA-617 at DC molar activities of 37–130 GBq·µmol⁻¹. Conclusions: A 2 h biomedical cyclotron irradiation and 5 h radiochemical separation produced GBq-scale ¹⁶⁵Er suitable for producing radiopharmaceuticals at molar activities satisfactory for investigations of targeted radionuclide therapeutics. This will enable fundamental radiation biology experiments of pure AE-emitting therapeutic radiopharmaceuticals such as [¹⁶⁵Er]PSMA-617, which will be used to understand the impact of AEs in PSMA-targeted radionuclide therapy of prostate cancer.