Synthesis of New 2,3-Disubstituted 4-Chloro-1-hydroxyindoles

The syntheses of new 2,3-disubstituted 4-chloro-1-hydroxyindoles were described. The conjugate nitro ketoester was reacted with various thiol and alcohol nucleophiles by the action of stannous chloride dihydrate through the unique processes of reduction of nitro group, intramolecular condensation, and addition of nucleophiles in one pot, to provide multisubstituted 1-hydroxyindoles. The reactions with thiol nucleophiles provided better results than those with alcohols, and, in particular, secondary and tertiary thiols provided best yields.

[1]  P. Hergenrother,et al.  Assessing the differential action on cancer cells of LDH-A inhibitors based on the N-hydroxyindole-2-carboxylate (NHI) and malonic (Mal) scaffolds. , 2013, Organic & biomolecular chemistry.

[2]  E. Giovannetti,et al.  Discovery of N-hydroxyindole-based inhibitors of human lactate dehydrogenase isoform A (LDH-A) as starvation agents against cancer cells. , 2011, Journal of medicinal chemistry.

[3]  K. Nicolaou,et al.  New synthetic technology for the construction of N-hydroxyindoles and synthesis of nocathiacin I model systems. , 2007, Tetrahedron.

[4]  K. Nicolaou,et al.  Synthesis of highly substituted N-hydroxyindoles through 1,5-addition of carbon nucleophiles to in situ generated unsaturated nitrones. , 2006, Angewandte Chemie.

[5]  K. Nicolaou,et al.  Construction of substituted N-hydroxyindoles: synthesis of a nocathiacin I model system. , 2005, Angewandte Chemie.

[6]  M. Spiteller,et al.  Birnbaumin A and B: two unusual 1-hydroxyindole pigments from the "flower pot parasol" Leucocoprinus birnbaumii. , 2005, Angewandte Chemie.

[7]  M. Somei.  Recent Advances in the Chemistry of 1-Hydroxyindoles, 1-Hydroxytryptophans, and 1-Hydroxytryptamines , 2002 .

[8]  M. Preobrazhenskaya,et al.  O-GLYCOSIDES OF N-HYDROXYINDOLES[1] , 2001 .

[9]  T. Takeuchi,et al.  MJ347-81F4 A & B, novel antibiotics from Amycolatopsis sp.: taxonomic characteristics, fermentation, and antimicrobial activity. , 1998, The Journal of antibiotics.

[10]  M. Somei,et al.  PREPARATIONS OF 1-HYDROXYINDOLE DERIVATIVES AND THEIR POTENT INHIBITORY ACTIVITIES ON PLATELET AGGREGATION , 1996 .

[11]  F. Bellamy,et al.  Selective reduction of aromatic nitro compounds with stannous chloride in non acidic and non aqueous medium , 1984 .