Sintese do sesterterpeno hyrtiosal a partir do acido copalico : determinação da configuração absoluta do produto natural
AUTOR(ES)
Ines Lunardi
DATA DE PUBLICAÇÃO
2002
RESUMO
In this work we reported the synthesis of sesterterpenes (-)-hyrtiosal, (+)-ent-hyrtiosal and their C-16 epimers, starting from 32% ee copalic acid isolated from comercial copaiba oil. Our interest for the synthesis of (-)-hyrtiosal and its enantiomer began due to its cytotoxic activity exhibited against KB cell in vitro and due to the absolute configuration was not established when the isolation was reported. During the course of synthesis, it was possible to make a resolution of mixture containing both enantiomeric alcohols at C-16, through (S)-O-methylmandelate esters, and also a mixture of C-16 epimeric alcohols. The determination of absolute configuration at C-16 of four stereoisomers was accomplished according to the model proposed by Trost using H NMR spectroscopy. The comparison of H and C NMR data and mainly the value of optical rotation observed for four final products with those reported in the literature for (-)-hyrtiosal, it was possible to confirm the absolute configuration of natural product. It was also accomplished a bioautography assays to evaluate antibacterial and antifungical activity and a cytotoxicity activity against larvae of brine shrimp Artemia salina with majority of synthesized compounds. None of assays exhibited significant bioactivities. The synthesized products (-)-hyrtiosal, (+)-ent-hyrtiosal, (-)-epi-hyrtiosal and (+)-epi-ent-hyrtiosal were also submitted for in vitro screening against nine lineage of cancerous cell at CPQBA/UNICAMP. Except for HT29, all compounds showed significant activity (0,1-25 mg/mL) against 8 lines of cancer cells. Major selectivity was observed for UACC (melanoma) cells and (-)-hyrtiosal showed to be the most active compound. (-)-Hyrtiosal and (-)-epi-hyrtiosal also showed best selectivity against leukemia cells. For the purpose of use isocopaladiene obtained in reasonable amount at the beginning of the synthesis of (-)-hyrtiosal as raw material in organic synthesis, it was performed several chemical reactions such ozonolysis and oxidation with OsO4, in order to obtain an useful intermediary for the synthesis of some marine norditerpenoids.
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ACESSO AO ARTIGO
http://libdigi.unicamp.br/document/?code=vtls000295342Documentos Relacionados
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