The Preparation and Intramolecular Radical Cyclisation Reactions of Chiral Oxime Ethers

Chiral oxime ether 2 and Oxime ester 4 have been prepared by alkylation and esterification of the oxime 1. Racemic hydroxylamine 6 and chiral hydroxylamine 10 have been synthesised from N-hydroxysuccinimide and the corresponding alcohol in the presence of diethylazodicarboxylate, the two products were converted into the oxime ethers 7 and 11 respectively. The intramolecular radical cyclisation reactions of these oxime ethers and esters has been studied, successful reaction was observed to produce alkyl hydroxylamines 3, 8 and 12. O éter-oxima quiral 2 e o éster-oxima 4 foram preparados para alquilação e esterificação da oxina 1. Hidroxiamina racêmica 6 e a hidroxiamina 10 foram sintetisadas a partir de N-hidroxipucanimida e o álcool correspondente na presença de di etil azodicarboxilato, e os dois produtos convertidos nos éteres-oximas 7 e 11 respectivamente. As reações de ciclização radicalar intramoleculares desses éteres e ésteres-oxima foram estudadas; a formação das alquil hidróxi-aminas 3, 8 e 12 foi observada nas reações bem sucedidas

The regiospecific Fischer Indole reaction in choline chloride.2ZnCl[subscript 2] with product isolation by direct sublimation from the ionic liquid

The Fischer indole synthesis occurs in high yield with one equivalent of the ionic liquid choline chloride·2ZnCl[subscript 2]; exclusive formation of 2,3-disubstituted indoles is observed in the reaction of alkyl methyl ketones, and the products readily sublime directly from the ionic liquid

Biphenyl-4-carboxylic Acid [2-(1<i>H</i>‑Indol-3-yl)-ethyl]-methylamide (CA224), a Nonplanar Analogue of Fascaplysin, Inhibits Cdk4 and Tubulin Polymerization: Evaluation of in Vitro and in Vivo Anticancer Activity

Biphenyl-4-carboxylic acid-[2-(1<i>H</i>-indol-3-yl)-ethyl]-methylamide <b>1</b> (CA224) is a nonplanar analogue of fascaplysin (<b>2</b>) that specifically inhibits Cdk4–cyclin D1 in vitro. Compound <b>1</b> blocks the growth of cancer cells at G₀/G₁ phase of the cell cycle. It also blocks the cell cycle at G₂/M phase, which is explained by the fact that it inhibits tubulin polymerization. Additionally, it acts as an enhancer of depolymerization for taxol-stabilized tubulin. Western blot analyses of p53-positive cancer cells treated with compound <b>1</b> indicated upregulation of p53, p21, and p27 proteins together with downregulation of cyclin B1 and Cdk1. Compound <b>1</b> selectively induces apoptosis of SV40 large T-antigen transformed cells and significantly reduces colony formation efficiency, in a dose-dependent manner, of lung cancer cells. It is efficacious at 1/10th of the MTD against human tumors derived from HCT-116 and NCI-H460 cells in SCID mouse models. The promising efficacy of compound <b>1</b> in human xenograft models as well as its excellent therapeutic window indicates its potential for clinical development