Goh, Teik Beng
(2015)
Isolation And Selective Reduction Of Mitragynine, Synthesis And Characterization Of New Indole Derivatives And Their Selected Biological Activity Studies.
PhD thesis, Universiti Sains Malaysia.
Abstract
Mitraginina (MGT) memiliki sifat analgesik yang poten tetapi ketoksikan MGT telah juga dilaporkan. Objektif utama tesis ini adalah untuk memencilkan MGT bagi pengubahsuaian lanjutan struktur dan juga untuk mensintesis terbitan indolnya bagi menilai aktiviti antiproliferatif, antioksida dan antinosiseptif masing-masing. MGT telah dipencilkan daripada daun M. speciosa dengan menggunakan prosedur penulenan yang ringkas dan berkesan. Pelbagai silana telah digunakan untuk menurunkan kumpulan karbonil dan ikatan dubel indol bagi MGT tetapi hanya ikatan berkembar indol telah berjaya diturunkan kepada indolina [CDR80 ((E)-metil 2-((2S,3S,12bS)-3-etil-8-metoksi-1,2,3,4,6,7,7a,12,12a,12b-dekahidroindolo[2,3-a]quinolizin-2-il)-3-metoksiakrilat)]. Tindak balas Pictet-Spengler telah diubahsuai dengan menggunakan 5-metoksitriptamina dan asid trifluoroasetik dalam medium akueus untuk mensintesis terbitan indol yang baru yang telah dicirikan dan dikenalpastikan sebagai CDR81 (6- metoksi-1-fenil-2,3,4,9-tetrahidro-1H-pyrido[3,4-b]indol) , CDR83 (6-metoksi-1-metil-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol), CDR82 (6-metoksi-1-(4-metoksifenil)-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol) dan CDR84 (2-metoksi-4-(6-metoksi-2,3,4,9-tetrahidro-1H-pirido[3,4-b]indol-1-l) fenol).
Mitragynine (MTG) possesses potent analgesic properties but the toxic effects of MTG have also been reported. The main objective of this thesis is to isolate MTG for further structural modification and also to synthesize its indole derivatives and evaluate their antiproliferative, antioxidant and antinociceptive activities. MTG was isolated from M. speciosa leaves using a simple and effective purification procedure. Various silanes were used to reduce the carbonyl and indole double bonds of MTG but only the indole double bond was successfully reduced to indoline [CDR80 ((E)-methyl 2-((2S,3S,12bS)-3-ethyl-8-methoxy-1,2,3,4,6,7,7a,12,12a,12b-decahydroindolo[2,3-a]quinolizin-2-yl)-3-methoxy acryl ate)]. The Pictet-Spengler reaction was modified using 5-methoxytryptamine and trifluoroacetic acid in an aqueous medium to synthesize new indole derivatives which were identified and characterized as CDR81 (6- methoxy-1-phenyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole), CDR82 (6-methoxy-1-(4-methoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole), CDR83 (6-methoxy-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole) and CDR84 (2-methoxy-4-(6-methoxy-2,3,4,9-tetrahydro-1H-pyrido[3,4- b]indol-1-l)phenol).
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