4-(2-Piperidyl)-1,3-dioxolanes with Local Anesthetic, Spasmolytic, and Central Nervous System Activity¹

Convenient Synthesis of Building-Blocks for Pyridine/Piperidine-Decorated Crown Ethers

“…While trying to hydrogenate 1-(pyridin-2-yl)ethane-1,2-diol hydrochloride in aqueous media according to the method of Hardie and co-authors, [17] we have observed no absorption of hydrogen at a pressure up to 130 bar and temperature of 110 o C. Also we tried to do hydrogenation in the presence of the Adams catalyst, and found that the results obtained were in a full agreement with the pioneer data of Adams, who stated, that platinum dioxide was effective for reduction of the pyridine ring under anhydrous conditions. [18] An attempt to carry out the above mentioned hydrogenation procedure with a mixture of palladium on charcoal and platinum oxide, according to the method of Jacobson and co-authors, [10] was also unsuccessful.…”

“…These improvements led us to a simple and effective protocol for the hydrogenation reaction, which avoids use of both high pressure and an external source of hydrogen. Moreover, to exclude the step of separation of two racemic mixtures of the target product, via formation and fractional crystallization and subsequent hydrolysis of their diphenylketals, [17] we have simply resolved them by subsequent fractional crystallizations from methyl tertbutyl and diethyl ethers ( Figure 5). Building-Blocks for Pyridine/Piperidine-Decorated Crown Ethers Conclusions 1-(Pyridine-2-yl)ethane-1,2-diol, 2-(oxirane-2-yl)pyridine and 1-(piperidine-2-yl)ethane-1,2-diol are considered as valuable starting materials for construction of crown ethers, decorated with pyridine and/or piperidine rings.…”

Synthesis and NMDA receptor affinity of fluorinated dioxadrol analogues

“…Dexoxadrol was synthesized by Hardie et al in the 1960s and revealed local anesthetic, spasmolytic, and central nervous system activity. 11 Later phencyclidine like dissociative anesthetic activities were found. 12 Unfortunately, clinical trials of dexoxadrol had to be stopped because of the psychotomimetic side effects.…”

Synthesis and NMDA Receptor Affinity of Ring and Side Chain Homologues of Dexoxadrol

“…[5] These efforts led to the enantiomerically pure compounds dexoxadrol and etoxadrol (Figure 1), which were clinically evaluated as analgesic and anesthetic drugs. [6,7] Unfortunately, in the clinical studies psychotomimetic side effects, unpleasant dreams and aberrations were observed, which brought the clinical evaluation to an end.…”