Estrogen receptor ligands. 12. Synthesis of the major metabolites of an ERalpha-selective, dihydrobenzoxathiin antagonist for osteoporosis

[reaction: see text] During the course of drug metabolism studies, a major metabolite of compound 1 was detected in rhesus monkeys and assigned structure 4. The intriguing biotransformation of 1 leading to 4 was confirmed by a 19-step total synthesis starting from resorcinol (11), the key feature of which was the construction of the oxygen bridge utilizing a phenolic oxidation and trapping sequence. In addition, the synthesis of a related metabolite (5) is described.     

The coherent potential approximation is a realizable effective medium scheme

The effective electrical conductivity of an aggregate, composed of grains of various conductivities, is frequently estimated by the coherent potential approximation, which embodies a local effective medium concept. It is proved rigorously that this approximation is exact for a wide class of hierarchical model composites made of spherical grains: the starting material 0 in the hierarchy is chosen arbitrarily, otherwise, materialj=1, 2, ... consists of equisized spheres, sayj-spheres, of arbitrary conductivities embedded in materialj — 1. The spatial distribution of thej-spheres must satisfy a mild homogeneity condition and their radiusr _j must, asymptotically, increase faster than exponentially withj. Furthermore, the minimum spacing, 2s _j , between thej-spheres is such that the ratios _j /r _j diverges. On the basis of these and some further ancillary conditions it is established that the coherent potential approximation becomes asymptotically exact for the effective conductivity of materialj. The results extend to other effective parameters of the composites, including the thermal conductivity, dielectric constant and magnetic permeability. In addition, the model composites and the proof of realizability may be generalized to allow non-spherical grains.     

Neutron activation analysis of semiconductor materials

Two examples of the use of neutron activation analysis for the characterization of semiconductor materials are given. 23 elements were determined in ASTM silicon intercomparison samples. Most elements are below the detection limits, which vary between 0.009–300 ng/g. CdS/CdTe thin films have been characterized by determining the Cd, Te, Cl, I and In concentrations of dissolved films. Parallel determinations in different samples of films prepared under identical conditions agreed within 0–53% (average deviation 21%) for Cl, Cd, In and I in CdS and 1.6–22% (average 8.7%) for Cd and Te in CdS/CdTe, respectively. It was determined both by NAA and resonance ionization spectrometry (RIS). The order of magnitude of the results was 1 ng/g and they agree within the range 7–64% (average difference 25%). The analytical procedures are described and discussed.     

Ligand dynamics and reactivity in trimetallic clusters

The general relationships between trinuclear cluster reactivity and the ligand dynamical processes in these systems are explored. Three specific mechanistic studies are presented: (1) the rate and stereochemistry of ligand addition to ₃-imidoyl complexes, (2) the factors influencing the rate of carbon-hydrogen bond activation in ₃-alkyne complexes, and (3) the origin of anomalously large kinetic deuterium isotope effect in metal to ligand and ligand to metal hydrogen transfer in trinuclear and binuclear complexes. In all three cases, the current state of the mechanistic studies are summarized and the possible rate of specific ligand dynamical processes in controlling the mechanism are put forth.