Year
2015
Degree Name
Doctor of Philosophy
Department
School of Chemistry
Recommended Citation
Shakoori, Alireza, Diversity oriented synthesis of fused heterocycles from the cascade reactions of indigo with allylic and propargylic systems, Doctor of Philosophy thesis, School of Chemistry, University of Wollongong, 2015. https://ro.uow.edu.au/theses/4497
Abstract
Diversity-oriented synthesis based on the cascade allylation chemistry of indigo, with its 2,2'-bisindolic system, has resulted in rapid access to new examples of the hydroxy- 8a,13-dihydroazepino[1,2-a:3,4-b']diindol-14(8H)-one (248-250) skeleton in up to 51% yield. Additionally the presence of the terminal substituent on the allylic substrates provided selectivity in production of 1-allyl-5'-allyloxy-3',4'-dihydrospiroindoline- pyrido[1,2-a]indol-ones systems (227-231) in up to 69%, where as the absence of the substituent on the terminal position of the allylic systems resulted in production of pyridoindolo-azepino[1,2-a]indol-11(7H)-ones heterocycles (232-236) in up to 72% yield. Quantitative generation of N-substituted indigo provided the mechanistic insights and preliminary measures to control the outcome of the cascade reactions. The base- induced propargylation of indigo resulted in the rapid one-pot synthesis of three different classes of heterocycles. The pyrazinodiindole 264 in 14%, pyridodiindole 265 in 17% yield and benzoindolonaphthyridinone 266 in 31% yield. The compounds 265 and 266 are possess the same framework of fascaplycin and ring B homologue, respectively. Further optimisation via alteration of the leaving group of the propargylic system from bromine to mesylate resulted in synthesis of the 265 and 266 with higher yields, 28% and 52% respectively. The presence of a phenyl substituent on the terminal alkynic position of the propargyl unit resulted in formation of oxadiazocinodiindole 271 in 62%. Initial biological activity studies with these new heterocyclic derivatives indicated promising in vitro antiplasmodial activity as well as good anticancer activity. The chemistry described is new for the indigo moiety and cascade reactions from this readily available and cheap starting material should be more broadly applicable in the synthesis of additional new heterocyclic systems, difficult to access by other means.
FoR codes (2008)
0304 MEDICINAL AND BIOMOLECULAR CHEMISTRY, 0305 ORGANIC CHEMISTRY
Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.