ABSTRACT
A total synthesis of (+)-conolidine has been achieved via the gold(I)-catalyzed cascade cyclization of a conjugated enyne. Remarkably, this strategy allowed for the simultaneous formation of the indole ring and the ethylidene-substituted piperidine moiety of (+)-conolidine under homogeneous gold catalysis in an enantioselective manner (88-91% ee).
ABSTRACT
A gold-catalyzed cascade cyclization of aniline derivatives bearing a conjugated diyne moiety was developed. Following the 5-endo-dig indole formation, subsequent 7-endo-dig cyclization predominated over 6-exo-dig cyclization to give the indole fused with a seven-membered ring in good yields.
Subject(s)
Aniline Compounds/chemistry , Diynes/chemistry , Gold/chemistry , Heterocyclic Compounds/chemical synthesis , Indoles/chemical synthesis , Catalysis , Cyclization , Heterocyclic Compounds/chemistry , Indoles/chemistry , Molecular StructureABSTRACT
Indole synthesis by a gold(I)-catalyzed intermolecular formal [4+2] reaction between 1,3-diynes and pyrroles has been developed. This reaction involves the hydroarylation of 1,3-diynes with pyrroles followed by an intramolecular hydroarylation to give the 4,7-disubstituted indoles. This reaction can also be applied to the synthesis of carbazoles when indoles are used as the nucleophiles instead of pyrroles.
Subject(s)
Diynes/chemistry , Gold/chemistry , Indoles/chemical synthesis , Pyrroles/chemistry , Catalysis , Diynes/chemical synthesis , Indoles/chemistry , Pyrroles/chemical synthesisABSTRACT
Two classes of fused nitrogen heterocycles were designed as CK2 inhibitor candidates on the basis of previous structure-activity relationship (SAR) studies. Various dipyrrolo[3,2-b:2',3'-e]pyridine and benzo[g]indazole derivatives were prepared using transition-metal-catalysed cascade and/or multicomponent reactions. Biological evaluation of these candidates revealed that benzo[g]indazole is a promising scaffold for potent CK2 inhibitors. The inhibitory activities on cell proliferation of these potent CK2 inhibitors are also presented.
Subject(s)
Casein Kinase II/antagonists & inhibitors , Copper/chemistry , Gold/chemistry , Heterocyclic Compounds/chemistry , Nitrogen Compounds/chemistry , Protein Kinase Inhibitors/chemical synthesis , Catalysis , Cell Line, Tumor , Cell Proliferation/drug effects , Heterocyclic Compounds/pharmacology , Humans , Models, Molecular , Molecular Structure , Nitrogen Compounds/pharmacology , Protein Kinase Inhibitors/pharmacology , Structure-Activity RelationshipABSTRACT
The gold-catalyzed cascade intermolecular addition-intramolecular carbocyclization reaction of dialkynylbenzenes was developed. In this reaction, regioselective addition of an external nucleophile toward the terminal alkyne and subsequent 6-endo-dig cyclization proceeded to give the 1,3-disubstituted naphthalenes in good yields. The direct synthesis of disubstituted chrysenes via a gold-catalyzed addition and double cyclization cascade using a triyne-type substrate was also achieved.
Subject(s)
Alkynes/chemistry , Gold/chemistry , Naphthalenes/chemistry , Naphthalenes/chemical synthesis , Catalysis , Cyclization , Molecular Structure , StereoisomerismABSTRACT
Polysubstituted dihydropyrazoles were directly obtained by a gold-catalyzed three-component annulation. This reaction consists of a Mannich-type coupling of alkynes with N,N'-disubstituted hydrazines and aldehydes/ketones followed by intramolecular hydroamination. Cascade cyclization using 1,2-dialkynylbenzene derivatives as the alkyne component was also performed producing fused tricyclic dihydropyrazoles in good yields.
