c 2.1, H20) (lit.3 [a]22D -86.9°(c 2.1, H20)).

An intermediate containing the ACE ring system of quassimarin was prepared. The isopropylidene malonate 8 reacted with diene 2 to afford two Diels-Alder adducts. The major adduct was converted into lactone 11 by a sequence involving epoxidation followed by acid-mediated epoxide opening and lactonization.

Carbaryl, an N-methyl carbamate (NMC), is a common insecticide that reversibly inhibits neuronal cholinesterase activity. The objective of this work was to use a hierarchical Bayesian approach to estimate the parameters in a physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model from experimental measurements of carbaryl in rats. A PBPK/PD model was developed to describe the tissue dosimetry of carbaryl and its metabolites (1-naphthol and "other hydroxylated metabolites") and subsequently to predict the carbaryl-induced inhibition of cholinesterase activity, in particular in the brain and blood. In support of the model parameterization, kinetic tracer studies were undertaken to determine total radioactive tissue levels of carbaryl and metabolites in rats exposed by oral or intravenous routes at doses ranging from 0.8 to 9.2 mg/kg body weight. Inhibition of cholinesterase activity in blood and brain was also measured from the exposed rats. Markov Chain Monte Carlo (MCMC) calibration of the rat model parameters was implemented using prior information from literature for physiological parameter distributions together with kinetic and inhibition data on carbaryl. The posterior estimates of the parameters displayed at most a twofold deviation from the mean. Monte Carlo simulations of the PBPK/PD model with the posterior distribution estimates predicted a 95% credible interval of tissue doses for carbaryl and 1-naphthol within the range of observed data. Similar prediction results were achieved for cholinesterase inhibition by carbaryl. This initial model will be used to determine the experimental studies that may provide the highest added value for model refinement. The Bayesian PBPK/PD modeling approach developed here will serve as a prototype for developing mechanism-based risk models for the other NMCs.

4‐Methoxy‐3‐penten‐2‐one product: 4‐methoxy‐3‐penten‐1‐one

No abstract

The application of high-resolution Fourier-transform nuclear magnetic resonance (NMR) spectroscopy to the identification of metabolites of the phosphorodithioate ester pesticide sulprofos (Bolster) was investigated. While differentiation between the various metabolites using either or 13C NMR was unsuccessful, 31P NMR proved to be an exquisitely sensitive probe for these compounds. Treatment of soil samples with sulprofos at a concentration of 7.4 ppm, followed by incubation for up to 90 days, led to the formation of two major metabolites. The residues were extracted, characterized, and quantitated using 31P NMR. Use of 14C radiolabeled material and analysis of extracts by high-performance liquid chromatography and liquid scintillation counting confirmed the results obtained by 31P NMR.

Syntheses of 5'-acyl furanosteroids are described from the corresponding unsubstituted [3,2-b]furanosteroids using acid anhydrides and acid chlorides in the presence or absence of Lewis acids. New methods have been developed to prepare 5'-acetyl derivatives: reduction of a 5'-trichloroacetyl intermediate either by sodium formaldehyde sulfoxylate or with 10% Pd/C. Most of these 5'-acyl derivatives bind to the rat ventral prostate androgen receptor. However the antiandrogenic activity was diminished when compared with 4,5'-methylsulfonyl furanosteroid. Biological studies revealed that 5'-acyl furanosteroids were either androgens or modest antiandrogens. The electrostatic potential maps of the substructures of 3, 4, and 5'-acetyl syn- and anti-furanosteroids showed striking differences which may explain, to some extent, the lack of significant antiandrogenic activity of 5'-acyl furanosteroids.

No abstract