Synthesis and single cell pharmacology of potential heterocyclic bioisosteres of the excitatory amino acid antagonist glutamic acid diethyl ester

A series of heterocyclic analogues of glutamic acid diethyl ester (GDEE), an antagonist at central excitatory amino acid receptors, have been synthesized and tested biologically. (RS)-Ethyl alpha-amino-alpha-(3-ethoxyisoxazol-5-yl)acetate (7), (RS)-ethyl 2-amino-3-(3-ethoxy-5-methylisoxazol-4-yl)propionate (16) and closely related analogues were synthesized. Compound 7, a diethyl derivative of the naturally occurring excitatory amino acid ibotenic acid (IBO), was synthesized from 3-hydroxy-5-methylisoxazole (1) via 3-ethoxyisoxazol-5-ylacetic acid (5) and its ethyl ester. Nitrosation of this ester followed by catalytic reduction gave 7. The ethyl ester of IBO, 9, was synthesized in a similar manner from 3-benzyloxyisoxazol-5-ylacetic acid (8). Ethyl derivatives of the synthetic excitatory amino acid 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) were synthesized from 3-hydroxy-4,5-dimethylisoxazole (10) through a diethyl acetylaminomalonate derivative, which upon deprotection gave the 3-ethoxy derivative of AMPA (15). Esterification of 15 gave the diethyl derivative 16 and the ethyl ester of AMPA (18) as well as N-ethylated derivatives of AMPA, 21 and 22 were synthesized. The final products were tested microelectrophoretically. The derivatives 7, 9, 15, 16 and 18 were weak and non-selective excitatory amino acid antagonists, whereas 21 and 22 were found to be inactive.     

Determination of ergosterol on mouldy building materials using isotope dilution and gas chromatography-tandem mass spectrometry

Ergosterol content of building materials was quantified using gas chromatography-tandem mass spectrometry (GC-MS-MS) in an ion trap with external ionisation. Hydrolysing the samples by classic extraction at 85 degrees C for 90 min in vials was faster, more precise and safer than microwave assisted extraction. [4-2H2]ergosterol was synthesised and used as internal standard, giving method standard deviation of 5-10% from 10 to 30 ng to 10-15 microg ergosterol in the sample. The use of GC-MS-MS meant that no solid-phase extraction clean-up was needed, so one person could easily prepare 40-80 samples per day.     

An unusual cosmological solution for λφ4 theory with broken symmetry

A particular solution to the Einstein equations is presented for an isotropic, spatially homogeneous and spatially flat space-time in the case that the matter field is that of a simple scalar ⁴ theory. The solution possesses unusual properties.