| Sažetak | U ovom radu opisan je dizajn i razvoj nove, ekonomične i brze elektrokemijske sinteze supstituiranih 1,3-oksazolidina iz vicinalnih amino-alkohola. Priređeni su derivati oksazolidina fuzionirani na desozamin (6 - 8) ili makrolaktonski prsten (11) azitromicina, koji su već ranije priređeni klasičnim metodama organske sinteze. Spomenuti spojevi pokazali su veliki potencijal za protuupalne primjene, stoga je ova efikasnija „zelena“ metoda odlična alternativa za sintezu ovih obećavajućih spojeva. Također, ova metoda testirana je i na manjim molekulama, pri čemu su uspješno priređeni (4S,5R)-N-benzil-3,4-dimetil-5-fenil-oksazolidin-2-imin 14 i N-benzil-1,3a,4,8b-tetrahidroindeno[1,2-d]oksazol-2-imin 17, kao nove potencijalno biološki aktivne molekule. Polazni materijali (odgovarajući amino-alkoholi) za sintezu makrolidnih oksazolidina (6, 7, 8 i 11) bili su demetilirani derivati azitromicina 1, 2 i 9, dok su za sintezu malih molekula 14 i 17 korišteni efedrin-hidroklorid 12 i
(1S,2R)-1-amino-2-indanol 15. Elektrociklizaciji je prethodila klasična sinteza odgovarajućih intermedijera metodama ranije opisanim u literaturi. Korišteni su benzil-izotiocijanat ili fenil-kloroformat kao reagensi, a reakcije su provođene u acetonitrilu uz trietilamin na sobnoj ili povišenoj temperaturi. Sve elektrociklizacijske reakcije provođene su u nepodijeljenoj ćeliji uređaja IKA ElectraSyn 2.0 uz C(+) – C(-) sustav elektroda i acetonitril kao otapalo te koncentraciju elektrolita (LiBr ili NaI) od 0.1 mM. Reakcije su provođene pri konstantnoj struji 5 – 10 mA s promjenom polariteta svakih 15 min. Za elektrokemijsku sintezu spojeva 6 i 14 isproban je i one-pot pristup polazeći od odgovarajućeg vicinalnog amino-alkohola (1 ili 12). Izvedba ovih one-pot reakcija provođena je na povišenoj temperaturi što je znatno usporilo sam korak ciklizacije. Ova metoda pokazala se boljom ne samo zbog svoje brzine i „zelenijeg“ pristupa, već je rezultirala i boljim iskorištenjima od klasičnih procesa. Strukture svih priređenih spojeva potvrđene su 1D i 2D NMR tehnikama. |
| Sažetak (engleski) | This paper describes the design and development of a new, economical and rapid electrochemical synthesis of substituted 1,3-oxazolidines from vicinal amino alcohols. Using this method, oxazolidine derivatives fused to desosamine (6 - 8) or macrolactone ring (11) of azithromycin, which had prior been prepared by classical methods, were synthesized. These compounds showed great potential for anti-inflammatory applications; therefore, this more efficient "green" method is an excellent alternative for the synthesis of these promising agents. Moreover, to test this method on smaller molecules,
(4S,5R)-N-benzyl-3,4-dimethyl-5-phenyloxazolidin-2-imine 14 and
N-benzyl-1,3a,4,8b-tetrahydroindeno[1,2-d]oxazol-2-imine 17 were prepared, as new potentially biologically active molecules. Starting materials (corresponding amino alcohols), for the synthesis of macrolide oxazolidines (6, 7, 8 and 11), were demethylated derivatives of azithromycin 1, 2 and 9, whereas for the synthesis of small molecules 14 and 17, ephedrine hydrochloride 12 and (1S,2R)-1-amino-2-indanol 15 were used. Electrocyclization was preceded by the classical synthesis of the corresponding intermediates, using methods previously described in the literature. Benzyl isothiocyanate or phenyl chloroformate were used as reagents, and reactions were carried out in acetonitrile with triethylamine at room or increased temperature. All electrocyclization reactions were carried out in an undivided cell of the IKA ElectraSyn 2.0 device with a C(+) – C(-) electrode system, acetonitrile as solvent and an electrolyte concentration (LiBr or NaI) of 0.1 mM. Reactions were carried out at a constant current of 5-10 mA with a change of polarity every 15 min. For the electrochemical synthesis of compounds 6 and 14, one-pot approach, starting from the corresponding vicinal amino alcohol (1 or 12), was tested as well. These one-pot reactions were carried out at an increased temperature, which significantly slowed down the cyclization step itself. This method proved itself to be better than classical synthesis not only because of its speed and "greener" approach, but also due to its greater yields. The structures of all compounds were confirmed by 1D and 2D NMR techniques. |
