Synthesis of 3,5-disubstituted-4-phenyl-2-pyrrolidones and their structural analogues

5-Alkil-4-fenil-3-metilēn-2-pirolidonu un to strukturālo analogu sintēze. Baškevičs V., Darba vadītājs: Dr. ķīm. Maksims Vorona. Maģistra darbs. 102 lappuses, 18 attēli, 30 pielikumi, 32 literatūras avoti. Latviešu valodā. Uz Morita-Baylis-Hillman reakcijas produktu bāzes realizēta to acilēšana un nitroalkānu pievienošanas starpproduktam. Iegūtie starpprodukti tika pakļauti reducēšanas reakcijai un iekšmolekulārai ciklizācijai ar eksometilēn grupu saturošo 2-pirolidonu veidošanu. Šim nolūkam bija izmēģinātas vairākas literatūrā eksistējošas 5-alkil-4-fenil-3-metilēn-2-pirolidonu iegūšanas metodes, no kuriem tika izvēlēta reducēšanas reakcija ar dzelzs pulvera palīdzību ledus etiķskābē. Iegūtie 3-metilēn-5-metil-4-fenil-2-pirolidoni un 3-metilēn-5-etil-4-fenil-2-pirolidoni bija sadalīti individuālos syn- un anti- stereoizomēros. Sintezētie 3,4,5-trīsaizvietotie pirolidoni tika transformēti attiecīgos N-acetamidos, alkilējot heterociklus ar brometiķskābes etilesteri un apstrādājot etil-2-(5-alkil-3-metilēn-4-fenil-2-oksopirolidīn-1-il)acetātus ar amonjaku. Sintezēto savienojumu struktūras tika pierādītas ar 1H un 13C KMR, 2d KMR, AIMS kā arī FTIR spektriem In vitro minēto 2-(2-oksopirolidīn-1-il)acetamīdu| 1R receptora alostērisko modulējošo īpašību testēšana paradīja to zemo efektivitāti šīs bioloģiskās aktivitātes jomā.Synthesis of 3,5-disubstituted-4-phenyl-2-pyrrolidones and their structural analogues. Baškevičs V., supervisor Dr. ķīm. Maksims Vorona. Master’s thesis. 102 pages, 18 figures, 32 literature references, 30 appendices. In Latvian. On the base of products obtained from Morita-Baylis-Hillman reaction there was realized their acylation and intermediates preparation by nitroalkane addition. Thus obtained derivatves were subjected to nitro group reduction and to intramolecular cyclization with the formation of 2-pyrrolidones containing exomethylene group in 3C position. Various methods mentioned in literature were tested for the preparation of 5-alkyl-4-phenyl-3-methylene-2-pyrrolidones. Reduction with iron powder in glacial acetic acid turned up to be most effective for this purpose. Thus obtained 3-methylen-5-methyl-4-phenyl-2-pyrrolydone and 3-methylen-5-ethyl-4-phenyl-2-pyrrolydone were separated into individual syn- and anti- stereo isomers. Synthesized 3,4,5-substituted pyrrolidones were transformed into corresponding N-acetamides by the alkylation of heterocyles with ethyl bromoacetate and following treatment of ethyl 2-(5-alkyl-3-methylene-4-phenyl-2-oxopirolidin-1-yl)acetates with ammonia. The structure of thus obtained compounds was proved by 1H and 13C NMR, 2d NMR, HRMS as well as with Thin Film Infra Red spectra. In vitro testing of 1R receptor allosteric modulating properties for synthesized 2-(2-oxopyrrolidin-1-yl)acetamides demonstrated their low effectiveness in this type of biological activity