В умовах перегрупування Шмідта дією азиду натрію на основі циклопентанону та циклогексанону із 2-піридиновим замісником у положенні а отримано 2-піридилзаміщені [формула], відповідно. Унаслідок кислотного гідролізу утворених лактамів отримано нові амінокислоти: відповідно 5-аміно-5-(піридин-2-іл)пентанову та 6-аміно-6-(піридин-2-іл)гексанову. Указані кислоти було вилучено й охарактеризовано як у формі гідрохлоридів, так і у вигляді електронейтрального цвітеріона.
В условиях перегруппировки Шмидта действием азида натрия исходя из циклопентанона и циклогексанона с 2-пиридиновым заместителем в положении а получены 2-пиридилзамещенные [формула], соответственно. Вследствие кислотного гидролиза лактамов получены новые аминокислоты: соответственно 5-амино-5-(пиридин-2-ил)пентановая и 6-амино-6-(пиридин-2-ил)гексановая. Данные кислоты были выделены и охарактеризованы как в форме гидрохлоридов, так и в виде електронейтрального цвиттериона.
This paper reports on the synthesis of new derivatives of 2-aminocaproic and 2-aminobutyric acid modified with a pyridin-2-yl substituent at the [formula]-position of the main chain. The hemostatic activity of both [formula]-aminocaproic acid itself and its various synthetic analogues is widely known. Likewise, numero&us [формула]- aminobutyric acid derivatives are strong neurotransmitters extensively used in the treatment of the nervous system disorders. No less popular are biologically active substances containing a pyridine or piperidine fragment; among which t&here are antibiotics, antimalarial, anti-sclerotic and antiallergic drugs, as well as anti-depressants and analgesics. Therefore, the introduction of the pyridine fragment into the amino acid structures is interesting in terms of their potential biol&ogical activity investigation. So, a method for the synthesis of 5-amino-5-(pyridin-2-yl)pentanoic and 6-amino-6-(pyridin-2-yl)hexanoic acid has been developed by us. The proposed scheme is based on the available reagents using. The key stage is the &Schmidt rearrangement of 2-(pyridin-2-yl)cyclopentanone and 2-(pyridin-2-yl)cyclohexanone, previously synthesized from pyridine N-oxide and cycloalkenyl morpholinide. For synthesized pyridine substituted cycloalkanones according to NMR spectroscopy, &the presence of keto-enol tautomerism was established. As a result of Schmidt rearrangement, lactams (2-(pyridin-2-yl)piperidone and 2-(pyridin-2-yl)azepanone) are formed, and the last ones had been hydrolyzed in an acidic medium to open the lactam c&ycle. Thus, 5-amino-5-(pyridin-2-yl)pentanoic and 6-amino-6-(pyridin-2-yl)hexanoic acid were isolated as hydrochlorides and the hydrochlorides were converted to the zwitterion form using propylene oxide. The first stage of the developed scheme (prepa&ration of pyridylalkanones) occurs in rather low yields, about 35 %. But, after the rearrangement, hydrolysis and the formation of zwitterion do not cause difficulties and are characterized by high yields. Consequently, the proposed synthetic sequenc&e is preparatively advantageous.
