Indole-3-carbinol → Indole-3-carbinol

Participants

Reaction Steps

As mentioned herein, many of the compounds studied were obtained from ChemBridge Corporation or from the NCI's Drug Synthesis and Chemistry Branch. The inventors also synthesized several dozens of analogs in their laboratory, e.g., 1-[1-(2-chlorobenzyl)-1H-indol-3-yl]ethanone, 1-[1-(3-chlorobenzyl)-1H-indol-3-yl]ethanone, 1-[1-(4-chlorobenzyl)-1H-indol-3-yl]ethanone, {1-[4-(trifluoromethyl)benzyl]-1H-indol-3-yl}methanol, 1-[3,5-bis(trifluoromethyl)benzyl]-1H-indole-3-carbaldehyde, {1-[3,5-bis(trifluoromethyl)benzyl]-1H-indol-3-yl}methanol, 1-(4-tert-butylbenzyl)-1H-indole-3-carboxylic acid, (1-(4-tert-butylbenzyl)-1H-indol-3-yl)methanol, 1H-Indole-3-carboxaldehyde, 1-[(3-methoxy-4-chlorophenyl)methyl], 1H-Indole-3-methanol, 1-[(3-chloro-4-fluorophenyl)methyl], Methanol, 1-[1-(b-D-glucopyranosyloxy)-1H-indol-3-yl], 1H-Indole-3-methanol,1-(b-D-ribofuranosyloxy), and 1H-Indole-3-biocytin-hydrazide, 1-[(4-chlorophenyl)methyl]-(9CI). Typically, two approaches were used to synthesize new analogs or analogs that are not commercially available. One approach was through reduction by LiAlH4 or NaBH4 or oxidation by KMnO4 of commercially available indole-3-carboxyaldehyde analogs to obtain indole-3-methanol or indole-3-carboxylic acid analogues. The second approach was to synthesize new compounds by using various compound building blocks as shown in FIG. 12. Briefly, 1.0 mmol of building block A (containing indole) was dissolved in anhydrous DMSO and mixed with 1.1 mmol of NaH. After 1 h of stirring at room temperature, 1.2 mmol of building block B (benzyl halides) was added, and the mixture was stirred at room temperature for another 24 h. Then, after the addition of distilled water (3× volume of DMSO), the mixture was extracted with chloroform or dichloromethane. The organic phase was washed with 10% NaCl. The water residue was then removed by adding anhydrous Na2SO4 which was in turn removed by filtering through a paper filter. The solution was then concentrated by rotary vacuum evaporation. The products were separated and purified by silica gel column chromatography based on the polarity of the compounds, using CH2Cl2:n-hexane (1:1) or CHCl3:methanol (20:1) as eluents, or by crystallization based on their solubility in various agents. The organic eluents were then removed by vacuum evaporation to obtain the final products. The purity and molecular weight of the final products were determined by high-performance liquid chromatography-mass spectrometry (HPLC-MS) (performed at the Pharmaceutical Development Center of our institution). The identities of the compounds were determined by nuclear magnetic resonance (NMR) analyses. The examples for HPLC-MS and NMR analysis for Oncrasin-27 after synthesis and purification are shown in FIG. 13. Most of the compounds had purity of >95˜99%, and their molecular weights matched the predicted molecule, as shown by HPLC-MS. Only compounds with a purity of 95% or higher shown by HPLC-MS were used for testing in cultured cells.

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