Disubstituted butanolides as potential antitumour agents: Design, synthesis and SAR investigation

U okviru ove doktorske disertacije ostvarena je prva totalna sinteza prirodnog γ-laktona, (-)-kleistanolata. Korigovana je predložena struktura prirodnog molekula primenom NMR spektroskopije, rendgeno-stukturne analize i merenjem ugla optičke rotacije. Sintetizovane su četiri serije analoga kleistanolata, uključujući i seriju enantiomernih analoga. Ispitana je antitumorska aktivnost sintetizovanih jedinjenja korišćenjem MTT testa. Primenom SAR analize, uspostavljene su korelacije između strukturnih fragmenata i antitumorske aktivnosti ka sintezi novog potentnijog osnovnog molekula.Within this doctoral dissertation, the first total synthesis of natural (-)- cleistanolate was done. Revision of the proposed structure of the natural molecule was done by NMR spectroscopy, X-ray analysis and optical rotation. Four series of cleistanolate analogues were synthesized. The antitumor activity of the synthesized compounds was investigated using MTT assay. In an attempt to identify structural features useful for cytotoxicity, the change of stereochemistry as well as the introduction of functional groups were studied for the possible structure-activity relationship