Domino approach to complex heterocycles
LE3 .A278 2015
Master of Science
In general, the work embodied in this thesis describes synthesis of two heterocyclic skeletons through a cascade approach. This work is a part of our work in devising new ways to generate novel quasisteroidal frameworks. Plausible mechanisms of the cascade process are proposed in both chapters. The first chapter investigates an efficient, environmentally benign, transition-metal free, tandem, C–N and C–O bond formation reaction development for the synthesis of tricyclic 7-oxa-2-azatricyclo[7.4.0.02,6]trideca-1(9),10,12-trien-3-ones and their analogs from easily available starting materials, including the renewable levulinic acid, a keto acid. The reaction of keto acids with methyl chloroformate and variously substituted o-aminobenzyl alcohols using triethylamine as a base in toluene at room temperature gave good to excellent yields. This newly developed protocol was successfully used for synthesis of a variety of polycyclic 7-oxa-2-azatricyclo-[7.4.0.02,6]trideca-1(9),10,12-trien-3-ones and related compounds. The desired tricyclic structure is considered as the building block of several plant alkaloids with different biological activities. The second chapter describes a concise method for synthesis of 14-azasteroid analogues with angular methyl group at C-13 of the steroidal nucleus. An interesting cascade reaction of arylacetylenes and N-(naphthalen-2-yl)pent-4-ynamides under gold(III)-catalysis to produce tetracyclic 12a-methyl-11-aryl-1,2-dihydrobenzo[f]pyrrolo[1,2-a]quinolin-3(12aH)-ones has been developed. xvi These tetracyclic compounds may be viewed as 14-azaestrogen analogs which would be employed in the development of selective estrogen receptor modulator for the treatment of breast cancer and osteoporosis.
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