862718-99-8

Upstream product

• 55289-35-5 2-bromo-6-nitrotoluene 
• 762-42-5 dimethyl acetylenedicarboxylate 
• 553-90-2 Dimethyl oxalate 

Downstream Products

• 850694-33-6 methyl 3-(2'-bromo-6'-nitrophenyl)-2-oxobut-3-enoate 
• 944472-32-6 (2S)-2-{[(2-{(1S)-1-[(tert-butoxycarbonyl)amino]-2-hydroxyethyl}-1,3-thiazol-4-yl)carbonyl]amino}-2-[4-(methoxymethyl)-1,3-thiazol-2-yl]ethyl 3-(2-bromo-6-nitrophenyl)-2-oxobut-3-enoate 
• 944472-31-5 tert-butyl (4S)-4-{4-[({(1S)-2-{[3-(2-bromo-6-nitrophenyl)-2-oxobut-3-enoyl]oxy}-1-[4-(methoxymethyl)-1,3-thiazol-2-yl]ethyl}amino)carbonyl]-1,3-thiazol-2-yl}-2,2-dimethyl-1,3-oxazolidine-3-carboxylate 
• 850694-42-7 3-(2-bromo-6-nitro-phenyl)-2-oxo-but-3-enoic acid 

Relevant academic research and scientific papers

One-pot synthesis of novel multisubstituted 1-alkoxyindoles

Studies on a one-pot synthesis of novel multisubstituted 1-alkoxyindoles 1 and their mechanistic investigations are presented. The synthesis of 1 was successfully achieved through consecutive four step reactions from substrates 2. The substrates 2, prepar

Synthesis and Antiproliferative Activities of 1-Hydroxyindole-2-Carboxylates

Synthesis and evaluation of antiproliferative activities of 1-hydroxyindole-2-carboxylates 1 were described. The toluene compounds 3 were treated with dimethyl oxalate and then, dimethylmethyleneammonium chloride to give intermediates 2. Compounds 2 were

Synthesis of New 1-Hydroxyindole-2-Carboxylates and Mechanistic Studies on Reaction Pathways

Synthesis of new 1-hydroxyindole-2-carboxylates 1 and mechanistic studies on the reaction pathways were described. The substrates 2, prepared through two-step synthetic sequences, were treated with nucleophiles in the presence of SnCl2 · 2H2O to obtain compounds 1. In particular, the mechanistic studies led to a significant finding that reactions with thiol nucleophiles occur through a newly proposed pathway (path B: 1,4-addition followed by reduction/condensation) rather than through a previously assumed pathway (path A: reduction/condensation followed by 1,5-addition). Further mechanistic investigations revealed steric effects of o-substituents in 2 governing the ratio of products (1i/7).

Synthesis of new highly substituted and hindered 1-hydroxyindole-2-carboxylates

The synthesis of new, highly substituted, and hindered 1-hydroxyindole-2-carboxylates 1 is described. Substrates 2, prepared through a two-step synthetic sequence, were treated with relatively weak nucleophiles in the presence of SnCl2 · 2H2O to afford compounds 1. In particular, nucleophiles of low reactivity and/or high steric hindrance reacted efficiently to give 1 in good to modest yields.

Discovery of N-hydroxyindole-based inhibitors of human lactate dehydrogenase isoform A (LDH-A) as starvation agents against cancer cells

Highly invasive tumor cells are characterized by a metabolic switch, known as the Warburg effect, from "normal" oxidative phosphorylation to increased glycolysis even under sufficiently oxygenated conditions. This dependence on glycolysis also confers a growth advantage to cells present in hypoxic regions of the tumor. One of the key enzymes involved in glycolysis, the muscle isoform of lactate dehydrogenase (LDH-A), is overexpressed by metastatic cancer cells and is linked to the vitality of tumors in hypoxia. This enzyme may be considered as a potential target for new anticancer agents, since its inhibition cuts cancer energetic and anabolic supply, thus reducing the metastatic and invasive potential of cancer cells. We have discovered new and efficient N-hydroxyindole-based inhibitors of LDH-A, which are isoform-selective (over LDH-B) and competitive with both the substrate (pyruvate) and the cofactor (NADH). The antiproliferative activity of these compounds was confirmed on a series of cancer cell lines, and they proved to be particularly effective under hypoxic conditions. Moreover, NMR experiments showed that these compounds are able to reduce the glucose-to-lactate conversion inside the cell.

New synthetic technology for the construction of N-hydroxyindoles and synthesis of nocathiacin I model systems

A new synthetic method providing expedient access to a wide range of polyfunctionalized N-hydroxyindoles (IV) is reported. These unique constructs are assembled by nucleophilic additions to in situ generated α,β-unsaturated nitrones (III) through carbon-carbon and carbon-heteroatom bond formation. The new synthetic technology was applied to the synthesis of nocathiacin I (1) model systems (2 and 3a-c) containing the N-hydroxyindole structural motif.

Synthesis of highly substituted N-hydroxyindoles through 1,5-Addition of carbon nucleophiles to in situ generated unsaturated nitrones

(Chemical Equation Presented) As easy as 1→2→3: Generation (1→2) and subsequent capture (2→3) of the reactive α,β-unsaturated nitrone species 2 with silyl enol ethers, silanes, and stannanes leads to a facile and direct entry to a variety of highly substi

Construction of substituted N-hydroxyindoles: Synthesis of a nocathiacin I model system

(Chemical Equation Presented) Generation (1→2) and trapping (2→3) of the fleeting α,β-unsaturated nitrone system 2 leads to the rare, biologically important N-hydroxyindole 3 in synthetically useful yields. This structural motif is found within the molecu