Design and Synthesis of Indole-Fused Diazocine, Diazepine and Triazole Fused-Benzoxazocinones of Biological Interest

• Main Authors: Tushar Ulhas Thikekar, 杜夏
• Other Authors: Sun, Chung-Ming
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/h4k3cw

博士 === 國立交通大學 === 應用化學系碩博士班 === 106 === This dissertation describes the development of new synthetic organic transformations by using metal free catalyst and with metal catalyst. Transition metal free catalyst transformations such as Pictet-Spengler reaction and with transition metal-catalyst transformation such as [5+2] annulation are described in this dissertation. For sake of convenience and better understanding, the thesis is divided into four chapters. The first chapter deals with the synthesis of structurally diverse indole-fused diazocine and diazepine derivatives. A substrate-based diversification approach of methyl-3- aminoindole/ indoline benzoates coupled with the Pictet−Spengler reaction and three different reaction cascades furnished indolodiazepine and indoloquinoxalines. The formation of indolodiazocines proceeds through an initial condensation followed by intramolecular alkylation. In the second chapter describes an efficient and regioselective Pd(II)-catalyzed [5+2] annulation of unprotected o-indolo anilines with internal alkynes under microwave irradiation. The diverse imine-containing 1,2-fused indole [1,7-a] diazepines are constructed in moderate to excellent yields. The mechanistic pathway shows pivalic acid and molecular oxygen to play crucial roles for the regeneration of highly active electrophilic Pd-species in the catalytic cycle. The third chapter emphasized the efficient and regioselective synthesis of novel 1,2,3- triazole-fused-1,5-benzoxazocinones through intramolecular cyclization of substituted ethynyl triazoyl benzoic acids. A crucial precursor 5-iodo-1,2,3-triazole benzoate was obtained from substituted 2-azido benzoic acid esters in a single step through a Copper- Catalyzed Azide−Alkyne Cycloaddition (CuAAC) reaction using a CuI/NBS catalytic system. A carbon−carbon triple bond was installed through a Sonogashira coupling reaction by various terminal alkynes. Finally, the 1,4,5-substituted ethynyl triazoyl benzoic acids were cyclized by a AgOTf mediated intramolecular cyclization to afford 8-endo-dig 1,2,3-triazolefused- 1,5-benzoxazocinones exclusively. The fourth chapter deals with a facile and efficient synthesis of novel oxo, thio and selenohydantoin fused tetrahydroazepino [4, 5-b]indoles. Naturally occurring iboga class alkaloid inspired seven-member azepino[4,5-b]indole ring was synthesized as a new scaffold through Pictet-Spengler reaction followed by skeletal rearrangement of aziridine ring. To improve the efficiency of the synthetic route, the double bond of the rearranged olefinic product was reduced and privileged hydantoin moiety was constructed on the core system through urea formation using variety of isocyanates, isothiocyanates and isoselenocyanates followed by intramolecular cyclization to incorporate elements of diversity. The regeneration of the double bond afforded hydantoin-fused tetrahydroazepino [4, 5-b]indoles.