The synthesis of lactam-containing derivatives of arylsulfonylglycine
Yu.E. Anisina, E.P. Kramarova, и Vad.V. Negrebetsky
Pirogov Russian National Research Medical University, 117997, Russia, Moscow,
Ostrovitianov str., 1
E-mail: julia4912@mail.ru
The interest in N-substituted lactams is their extremely wide spectrum of biological activity.
As examples of the variety of their physiological effects can shown nootropics «Nootropil»
(«Piracetam») and «Phenotropil», antiepileptic drug «Keppra», anticoagulant «Apixaban». The
most perspective among the methods of synthesis of these compounds is the reaction of N-silylated
lactams with various alkylating and acylating agents.
In the first stage there were synthesized N-trimethylsilyllactams (1a-d) by treatment of
lactams, which are the unsubstituted on nitrogen, by trimethylchlorosilane or hexamethyldisilazane
under reflux [1], and also there were synthesized N-organosulfonyl derivatives of amino acid
glycine in water at the Schotten-Baumann reaction [2]. Next N-substituted acids were converted
into the corresponding acid chlorides using thionyl chloride and a catalytic amount of DMF (2a-d).
After synthesis of the starting compounds was possible to obtain a target sulfonamides. All
reactions were carried out in absolute solvents [1, 3]. At the first there was synthesized a number of
derivatives of 4-phenylpyrrolidin-2-one (3aa-ad), then there was synthesized a number of
pyrrolidin-2-one (3ba-bd). However in the case of derivatives of piperidin-2-one (3ca-cd), only
methyl derivative (3ca) has been allocated with a good yield, synthesis of derivatives azepan-2-one
(3da-dd) did not result in the target products (even by varying of conditions).
Structures of new compounds were confirmed by IR spectroscopy, NMR (1H and
elemental analysis.
References
[1] M. Rothe, Chemische Berichte. 1966, 99, 3820-3829.
[2] J. DeRuiter, Journal of pharmaceutical sciences. 1987, 76, 149-152.
[3] L. Birkofer, Chemische Berichte. 1960, 93, 2804-2809.
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