Studies On Bioinspired Synthesis Of Benzo-fused Azoles, 2-aminoindoles And Cyclotryptamines

Nitrogen heterocycles such as benzo-fused azoles,2-aminoindoles and cyclotryptamines are present in a variety of natural products and medicinally important compounds. Intrigued by efficient chemical reactions and elegant pathways for synthesis of the natural products in organism, this dissertation focuses on bioinspired synthesis of nitrogen heterocycles. The main body of the present dissertation consists of two parts. In the first part, benzoxazoles, benzimidazoles and indoles were efficiently synthesized by the reaction of ortho-substituted nitrobenzene derivatives with Hantzsch 1,4-dihydropyridine, a biomimetic reducing agent in the presence of catalytic Pd/C. In the second part, the coupling reactions of tryptophan derivatives in acidic or oxidative conditions were studied for biomimetic synthesis of cyclotryptamine alkaloids. The results are obtained as following:1. Hantzsch 1,4-dihydropyridine, analogues of NAD(P)H, was develped as an efficient reducing agent in reductive cyclization of ortho-substituted nitrobenzene derivatives. In the presence of Pd/C as a catalyst, the tandem reduction and intramolecular cyclization gave corresponding benzoxazoles, benzimidazoles and indoles. On the basis of hydrogen evolution experiment and DFT calculations, we believe that the present reductive cyclization is very efficient and ortho-substituted nitrobenzene is reduced by palladium hydride generated from HEH in the presence of Pd/C.2. The dimmers, trimers, and higher-order oligomers of tryptamine are the most abundant indoline alkaloids present in nature. The biological pathways for the synthesis of these cyclotryptamines may involve the 3,3'-coulpling or 3,7'-coulpling of tryptamines or tryptophans. We proposed that the free radicals or positive ions of tryptophan are the key intermediates existed in the biosynthesis and the stereoselectivities of reactions arise from tryptophan units. Therefore, a variety of tryptophan derivatives were tested in oxidative or acid-catalyzed conditions. Although the desired 3,3'-coulpling or 3,7'-coulpling products were not achieved, we obtained some important products such as 2,2'-coulpling and 2,6'-coulping products. The present work is fundamental to biomimetic synthesis of cyclotryptamines.