Xiaohu Ouyang

Solid support synthesis of 2-substituted dibenz[b,f]oxazepin-11(10H)-onesvia SNAr methodology on AMEBA resin

Abstract Efficient assembly of dibenz[b,f]oxazepin-11(10H)-ones utilizing the SNAr of fluorine in 2-fluoro-5-nitrobenzoic acid with the OH of various 2-aminophenols on solid support is reported. The flexibility of this synthesis, as well as the excellent purity (>90%) of the final products are the distinctive characteristics of the resulting library.

Novel and Highly Efficient Synthesis of Substituted Dibenz[b,g]1,5-oxazocines. A Direct Comparison of the Solution versus Solid-Phase Approach

Abstract We describe a novel and highly efficient synthesis of substituted dibenz[ b , g ]1,5-oxazocines. The procedure is based on the S N Ar of fluoride with the phenolic hydroxide of the properly assembled acyclic intermediate. A direct comparison of the solution-phase vs the solid-phase synthesis has been conducted. The speed of the synthesis, the purity of the desired eight-membered heterocycles (>95%), as well as the diversity of the resultant library are definite advantages of the solid-phase procedure. Yields of dibenz[ b , g ]1,5-oxazocines synthesized via the solid-phase approach were generally better, while the purity of the products synthesized by both methods were identical.

Discovery of Dual VEGFR-2 and Tubulin Inhibitors with in Vivo Efficacy.

In an effort to develop potent, orally bioavailable compounds for the treatment of neoplastic diseases, we developed a class of dual VEGFR-2 kinase and tubulin inhibitors. Targeting the VEGFR receptor kinase and tubulin structure allows for inhibition of both tumor cells and tumor vasculature. Previously, a combination of two compounds, a VEGF receptor tyrosine kinase inhibitor and tubulin agent, was demonstrated to produce an enhanced antitumor response in animal studies. We have reaffirmed their results, with the added benefit that both activities are found in one compound.

Novel synthesis of dibenzo[b,g]1,5-oxazocines

An efficient approach to dibenzo[b,g]1,5-oxazocines on solid support is described. The procedure is based on the intramolecular nucleophilic aromatic substitution of fluorine from the derivatives of 2-fluoro-5-nitrobenzaldehyde with the OH function of immobilized phenols. Good yields, and excellent purities of the targeted heterocycles are the advantages of the reported procedure.

Fast and efficient synthesis of substituted dibenz[b,f]oxazocines on solid support

Abstract An efficient synthesis of substituted dibenzazocines on solid support is described. The targeted heterocycles are assembled via the nucleophilic aromatic substitution of fluorine in 2-fluoro-5-nitrobenzoic acid with the OH function of the immobilized polysubstituted phenols. High yields and excellent purities of the final products are the distinct characteristics of the resultant 15-member library.