Expanding Stereochemical and Skeletal Diversity Using Petasis Reactions and 1,3-Dipolar Cycloadditions

A short and modular synthetic pathway using intramolecular 1,3-dipolar cycloaddition reactions and yielding functionalized isoxazoles, isoxazolines, and isoxazolidines is described. The change in shape of previous compounds and those in this study is quantified and compared using principal moment-of-inertia shape analysis.Chemistry and Chemical Biolog

Pharmacological Effects of Asiatic acid in Glioblastoma Cells under Hypoxia

Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Despite current treatment options including surgery followed by radiation and chemotherapy with temozolomide (TMZ) and cisplatin, the median survival rate remains low (<16 months). Combined with increasing drug resistance and the inability of some compounds to cross the blood brain barrier (BBB), novel compounds are being sought for the treatment of this disease. Here, we aimed to examine the pharmacological effect of Asiatic acid (AA) in glioblastoma under hypoxia. To investigate the effects of AA on cell viability, proliferation, apoptosis and wound healing, SVG p12 fetal glia and U87-MG grade IV glioblastoma cells were cultured under normoxic (21% O2) and hypoxic (1% O2) conditions. In normoxia, AA reduced cell viability in U87-MG cells in a time and concentration-dependent manner. A significant decrease in viability, compared to cisplatin, was observed following 2hrs of AA treatment with no significant changes in cell proliferation or cell cycle progression observed. Under hypoxia, a significantly greater number of cells underwent apoptosis in comparison to cisplatin. While cisplatin showed a reduction in wound healing in normoxia, a significantly greater reduction was observed following AA treatment. An overall reduction in wound healing was observed under hypoxia. The results of this study show that AA has cytotoxic effects on glioma cell lines and has the potential to become an alternative treatment for glioblastoma

Diastereoselective cycloadditions of nitrilimines to enantiopure acrylamides

The diastereoselective cycloaddition of the nitrilimine 2 with enantiopure acrylamides 3 was exploited to obtain enantiopure 4,5-dihydropyrazoles 4 and 5. Basic hydrolysis of the cycloadducts gave the dicarboxy derivatives 6 and 7 or 8 and 9, which are of potential interest as new chiral building blocks. (C) 2002 Elsevier Science Ltd. All rights reserved

L-alanine benzylester as chiral inductor: Synthesis of enantiopure pyrazolo[1,5-a]-[1,4]benzodiazepine-4-ones via intramolecular nitrilimine cycloadditions

The title compounds, of potential pharmacological interest, have been obtained in the enantiopure form through a stereoselective intramolecular 1,3-dipolar cycloaddition of homochiral nitrilimines 5

Asymmetric induction by the (S)-1-phenylethyl group in intramolecular nitrile imine cycloadditions giving enantiopure 3,3a-dihydro-pyrazolo[1,5-alpha][1,4]benzodiazepine-4(6H)-ones

Stereoselective intramolecular cycloadditions of homochiral nitrile imines 5 are described as a fruitful source of enantiopure 3,3a-dihydro-pyrazolo[1,5-a][1,4]benzodiazepine-4(6H)-ones 6 and 7. (C) 1999 Elsevier Science Ltd. All rights reserved