Studies On The Construction Of The Common Core Scaffolds Of A Series Of Biologically Active Natural Products Based On The Domino Reactions Involving α-Isocyanoacetates

cis-3a,8a-Hexahydropyrrolo[2,3-b]indole and cis-3a,8a-hexahydropyrrolo[2,3-b]benzofuran are common core scaffolds of a large array of biologically active natural products. Regarding the shortcomings that the starting materials were always not easily available, the synthetic routes were always lengthy, the overall synthetic efficiency was always very low, and the atom economy was often very bad, accompanied with the traditional construction methods of these scaffolds, this thesis develops two kinds of novle, mild and efficient syntheitc methods by taking advantage of readily available substrates as starting materials. The main content includes:First, the studies on the construction of hexahydropyrrolo[2,3-b]indole scaffold based on Cu(I) or Ag(I) catalyzed domino reactions involving isocyanoacetates and2-(2-amidophenyl)acrylates. By taking advantage of readily available2-(2-amidophenyl)acrylates and isocyanoacetates as substrates, a novle, mild, efficient and atom-economic method for the synthesis of hexahydropyrrolo[2,3-b]indole scaffold, which was the key common scaffold in many biologically active natural products, had been developed. The reaction could be performed under the conditons that CuI and K2CO3 were used as cocatalysts, acetonitrile was used as a solvent, the reaction temparature was 80 oC, and the reaction time was 3 hours, or that Ag2 O and K2CO3 were used as cocatalysts, and the reaction temparature was room temparatre,giving the desired products in high yields. The studies on the reaction scope reveald that a large variety of functional groups were compatible with this reaction. Based on the series of experimental results, a possible reaction mechanism had been proposed.Second, the studies on the efficient assembly of enantioenriched hexahydropyrrolo[2,3-b]indole scaffolds by Ag(I)-catalyzed asymmetric domino reaction in the presence of chiral P ligands. By employing cincona-derived chiral P ligands, a novel method for the assembly of enantioenriched hexahydropyrrolo[2,3-b]indole scaffolds, taking advantage of a novel and efficient asymmetric domino reaction, had been developed. When using AgNO3 or Ag2 O as acatalyst, this reaction could be conducted in acetonitrile at room temparature for 6 to24 hours by utilizing cincona-derived chiral P as chiral ligands, producing the desired products in high yields and good enantioselectivities. The studies on the reaction scope indicated that various functionalities could be tolerated in this reaction,affording a novel pathway for the construction of enantioenriched hexahydropyrrolo[2,3-b]indole scaffolds with divergent functionalities.Third, the studies on the synthesis of enantioenriched hexahydropyrrolo[2,3-b]benzofuran scaffolds through Ag(I)-catalyzed asymmetric domino reaction. By using cincona-derived chiral P ligands, a novel asymmetric domino reaction involving isocyanoacetates and 2-(2-hydroxyphenyl)acrylates, which could be used for the efficient assembly of enantioenriched hexahydropyrrolo[2,3-b]benzofuran scaffolds, had been investigated. Under the conditions that Ag2 O was used as a catalyst, and cincona-derived P ligands was used as a chirality-controlling element, the reaction could be performed in acetonitrile at-20 oC for 24 hours, producing the disired products in high yields and good enantioselectivities. Preliminary reaction scope studies indicated that this reaction was compatible with a variety of functional groups, offerring a novel and economic synthetic method for the chiral hexahydropyrrolo[2,3-b]benzofuran scaffolds.