Résumé confidentiel / Résumé confidentiel

MSc (Chemistry) / Department of Chemistry

<p>Within this doctoral thesis, eighteen new compounds, polycyclic polyprenylated<br />acylphloroglucinols, were isolated from petrol ether extract of <em>Hypericum barbatum</em><br />plant. The compounds are named hyperibarbins A&ndash;R. For hyperibarbins A&ndash;D,<br />cytotoxicity towards carcinogenic cells and antibacterial activity were evaluated. All<br />four compounds exhibited intermediate activity towards tumor cells in vitro. Although<br />inactive towards Gram negative bacteria, examined compounds have expressed<br />extraordinary bacteriostatic activity towards Gram positive bacterial strains.<br />Hyperibarbins C, E, N and K were, since having endoperoxide bridge in their structures,<br />tested for antiprotozoal activity, but shown intermediate activity towards the examined<br />parasite strains. All goals set for this doctoral thesis at the beginning have been fully<br />met, with isolation of new compounds, described andcompletely chemically<br />characterized for the first time.</p> / <p>U okviru ove doktorske disertacije izolovano je osamnaest novih jedinjenja, policikličnih&nbsp; poliprenilovanih acilfloroglucinola, iz petroletarskog ekstrakta biljke <em>Hypericum&nbsp; barbatum</em>. Imena jedinjenja su hiperibarbini A&ndash;R. Za hiperibarbine A&ndash;D, ispitana je&nbsp; citotoksičnost prema kancerogenim ćelijama i antibakterijska aktivnost. Sva četiri&nbsp; jedinjenja su ispoljila srednju aktivnost prema tumorskim ćelijama <em>in vitro</em>.&nbsp; Iako neaktivni&nbsp; prema Gram negativnim bakterijama, ispitana jedinjenja su ispoljila izuzetnu bakteriostatsku aktivnost prema sojevima Gram pozitivnih bakterija. Hiperibarbini C, E, N i K su, zbog posedovanja endoperoksidnog prstena u svojoj strukturi, testirana na antiprotozoalnu aktivnost, ali su pokazali srednju aktivnost prema ispitanim sojevima parazita. Svi ciljevi postavljeni na početku izrade ove doktorske disertacije su do kraja ispunjeni, sa izolacijom novih, prvi put opisanih i u potpunosti hemijski okarakterisanih jedinjenja.</p>

Polycyclic polyprenylated acylphloroglucinols (PPAPs) are plant- (Guttiferae) derived natural products. They have fascinating bicyclo[3.3.1]nonane-2,4,9-trione or [3.2.1]nonane-2,4,8-trione cores decorated with prenyl or geranyl groups. More than 200 PPAPs have been isolated, but only a few of them have been synthesized, although most of the synthesized PPAPs are of type A and have an exo substituent at C (7). Here, we are trying to make a type B 7-endo PPAP, 7-epi-clusianone. The synthetic plan involves an alkynylation–aldol strategy to construct the bicyclic core. Having established the bicyclic core, the synthesis presents a new challenge: the oxidation of a very hindered 2-alkenone to the β-hydroxy 2-alkenone.