Gold-catalyzed Cascade Cylization Of Ynones And Its Applications

The past decade has witnessed the significant progress of homogeneous gold catalysis as a powerful tool in organic synthesis for the construction of molecules of varying complexity.In particular,gold-catalyzed alkyne oxidative cascade cyclization reactions have been also systematically developed.In this thesis,a novel gold?III?-catalyzed oxidative cascade reaction of ynones with distinctive reaction mechanism was developed accoding to the unique properties of gold?III?and the conjugated acetylenic ketones.Moreover,five novel types of polycyclic compound libraries with potential bioactivities were constructed and the biological activities of the obtained products were tested and several bioactive candidates possessing potential antibacterial activity were screened out.The specific results are as follows:1)A selective oxidation of ynone moiety of 1,6-diynes-8-one derivatives to trigger cascade cyclization to construct furan-fused 2H-pyrone derivatives was achieved with KAuCl₄ 2H₂O as catalyst and 2,6-dichloropyridine N-oxide as oxidant.This reaction showed a broad substrate scope and 31 desired products were obtained.In particular,substrates bearing skeletons of natural products such as Menthol and Sterol were also well tolerated.Moreover,these products were easily subjected to further transformations and structurally diverse derivatives could be obtained via reduction,oximation reaction,Aldol reaction and Diels-Alder reaction.When it comes to the reaction mechanism,kinds of control experiments were carried out and the results indicated that the mechanism of this reaction was a concerted S_N2'type process,which was different from the classical mechanism that involving carbene intermediate.Therefore,we have sought out a novel action mechanism between gold?III?and ynones in the cyclization reactions.2)An oxidative cyclization of?-phenoxyl ynone derivatives to construct 4-substituted chroman-3-one derivatives was developed using PicAuCl₂ as catalyst and2,6-dichloropyridine N-oxide as oxidant.This reaction showed a broad functional group tolerance and the target products having novel structures involving stable enol unites were obtained in high yields.Additionally,1-phenoxyl-2,5-diyne-4-one derivatives were successfully employed to construct the potential bioactive chroman-fused pyranone derivatives via cascade reactions that triggered by PicAuCl₂ catalyzed selective oxidation of2-alkynyl groups.Moreover,several control experiments were carried out and the results indicated that this reaction proceed via a novel concerted S_N2'process through the allenyloxy-gold?III?intermediate,which was different from the classical sp² C-H insertion mechanism.Further,the derivation of product 3-3e paved a novel and efficient way for synthesizing the skeleton of rotenone.3)An unprecedented gold?III?-catalyzed cyclization for the selective assembly of polycyclic compounds from ynones bearing alkylidenecyclopropane moiety was accomplished.The substrates underwent a formal[3+2]cycloaddition reaction to establish the cyclopentene-fused indene derivatives under the catalysis of PicAuCl₂ combined with2,6-dichloropyridine N-oxide which did not act as an oxidant but still played a vital role in this reaction.When the oxidant was changed to 8-Me-quinoline N-oxide,an oxidative cyclization reaction occurred to construct cyclobutane-fused naphthalenone derivatives.This reaction showed a broad functional group tolerance and high selectivity and the desired products were obtained in high yileds.Subsequent mechanism studies indicated that the N-oxides played a decisive role in this reaction.4)Finally,we tested the biological activities of the obtained products.The cytotoxicity of these products were evaluated by the MTT method against two cancer cell lines:A549and HT29.The results indicated that compounds 2-3m,3-3l and 3-4x exhibited moderated cytotoxic activity against A549 cell lines and compounds 2-3j,2-3l,3-3l and 3-4x showed moderated cytotoxic activity against HT29 cell lines at a concentration of 10?M.Moreover,the antibacterial activities of all the products were evaluated against five pathogens:Bacillus cereus?B.c?,Bacillus subtilis?B.s?,Ralstonia solanacearum?R.s?,Pseudomonas solanacearum,Methicillin-resistant Staphylococcus aureus?MRSA?,Staphylococcus aureus?S.a?.The results indicated that compound 3-3l exhibited strong inhibition against S.a with an inhibition rate of 99%at a concentration of 35?g/mL.Compound 4-3h showed promising inhibition against the five pathogens with inhibition rates around 90%.Further,the minimal inhibitory concentrations?MICs?of compounds 3-3l and 4-3h were tested.And the results showed that the MICs of compounds 3-3l and 4-3h were 32?g/mL and 2?g/mL,which was comparable to the positive control,against Staphylococcus aureus and Ralstonia solanacearum,respectively.