Synthesis, stereochemical analysis, and neuromuscular blocking activity of oximino ether derivatives of progesterone

This study consists of the synthesis, separation, and stereochemical analysis of oximino ethers, followed by a preliminary pharmacological evaluation for neuromuscular blockade. Synthesis of the compounds began with the double oximation of progesterone, which yielded EE and ZE dioximes as major products. Both stereoisomers were separated and purified by chromatography followed by crystallization. The diether of each dioxime was prepared by O-alkylation with 2-dimethylaminoethyl chloride hydrochloride, using a mixture of potassium tert-butoxide and sodium hydride as base. The diethers were separated from the monoethers by vacuum chromatography. Configurational assignments of all compounds were based on 1HNMR and 13CNMR spectroscopy. Quaternization with methyl bromide yielded the salts which were purified via fractional crystallization. A preliminary pharmacological evaluation was conducted by using mice on a treadmill apparatus. Structure-activity relationships are discussed on the basis of similarities to succinylcholine.