Application of the Cleavable Isocyanide in Efficient Approach to Pyroglutamic Acid Analogues with Potential Biological Activity

Two efficient procedures have been developed for the synthesis of pyroglutamic acid analogues 28, 29, and 34. According to the first method the Ugi (4C3C) reaction is followed by a post-transformation reaction, and the second method involves the Michael addition reaction. The present methodologies demonstrate the applicability of 1-(2,2-dimethoxyethyl)-2-isocyanobenzene (15) as a cleavable isocyanide in the Ugi/ post-transformation reaction and a strong nucleophile in the Michael addition reaction. The framework of pyroglutamic acid analogues has been constructed by the selective cleavage of the C-terminal amide bond and nucleophilic addition to the activated α,β-unsaturated carbonyl group.

     

Titrimetric Microdetermination of chloral hydrate by amplification reactions

A simple titrimetric method for estimation of 0.1–5 mg of chloral hydrate is presented. It depends on oxidation of an alkaline solution of chloral hydrate with a chloroform solution of iodine, removal of excess of iodine, oxidation of the resulting iodide with bromine, and iodometric titration of the iodate produced, giving 6-fold amplification. Alternatively, the iodide formed is oxidized with periodate, masking of the excess of periodate with molybdate at pH 3, and iodometric titration of the iodate, giving 24-fold amplification. The coefficient of variation does not usually exceed 2%, for above 1 mg of chloral hydrate but increases to 3.8% at the 0.1-mg level.