Studies On The Synthesis Of Natural Bis-indole Alkaloid Analogs And On The Cyclization Of α, β-unsaturated Indolones

This dissertation aims at the studies on synthesis of natural bis-indole alkaloid analogs and on cyclization of α,β-unsaturated indolones. It consists of the following four parts;I . 1. Synthesis of the key precursor (57) of analogues of yuehchukene, a bis -indole alkaloid having anti -implantation activity and anti-inflammatory activity,was accomplished starting from indole and acrylic acid through Severn steps by employing the Diels -Alder cycloaddition reaction of indole diene (5) with acrylic acid and the cyclization of compound (48) in PPE as key steps. The unexpected product (51) was also obtained and its reaction mechanism indicated that it was an unusual "dehydration": the lose of two H's and concomitant exocyclic (to the aromatized carbocycle) removal of the carbonylic oxygen-2. Synthesis of the key precursor (28) of yuehchukene was accomplished starting from indole and malonic acid through nine steps by employing the Diels -Alder cycloaddition reaction of indole diene (5) with compound (61) and the cyclization of compound (63) in PPE as key steps.II . Seven new bis-indole alkaloids were synthesized from indole through five steps. The key step in the synthesis is the cyclization of α,β-unsaturated indolone in lewis acid The comformation of the reduction product of indole cyclic ketone (70) with NaBH₄ was described and their corresponding ¹H-NMR and NOE spectra were explained.III . The cyclization of α,β-unsaturated indolones in different lewis acids was studied carefully by changing the side chain , electron density and space volume of α,β-unsaturated indolones. The results indicated that :(1)α,β-unsaturated indolones were treated in proton lewis acids and aprotic lewis acids respectively to give products with different structural features . (2) Treated with ACl₃. The product of the cyclization of α,β-unsaturated indolones relied on the moleculer bulk. (3) The reaction mechanism of the cyclization of α,β - unsaturated indolones in lewis acids was the formation of carbonium ion was firstly induced by lewis acid and the the carbonium ion attacked the indole or the carbonium ion rearranged to the new carbonium ion and then the new carbonium ion attacked the indole to form the indole cyclic ketone.IV. Some of synthesized compound were tested for anti-inflammatory activity and the results indicated that the inhibition ratio of compound (48) is 100% to LTB₄ at 10^-4M.Finally, the thesis concerns the synthesis of sixty-seven compounds among which fourty - three were previously unreported.