Synthesis of benzothiazinones benzothiazines and their selenium analogues through novel synthetic routes

Abstract

Benzo fused N-heterocyclic scaffolds containing oxygen, sulphur or selenium have found wide interest in the field of drug-discovery. Among these N-heterocycles, benzothiazine, benzoxazine, benzoselenazine and benzothiazinone derivatives are a unique class of compounds and have a larger scope towards the development of efficient and simple synthetic methodologies for their synthesis with readily available substrates. newlineDuring the course of the present thesis a convenient and simple synthetic procedures were developed for the synthesis of benzothiazines, benzoxazines, benzoselenazines and benzothiazinones in an onepot methodology. 2-aryl/alkyl substituted 1,3-benzothiazines and selenazines were synthesized by reacting 2-amino benzyl alcohols and thio or seleno benzamides in the presence of T3P.A reagent controlled methodology was developed for the synthesis of 2-amino substituted 1,3-benzothiazines and oxazines. Initially, various 2-amino benzylalcohols are reacted with newlineisothiocyanates to form the corresponding thioureas. The formed thioureas undergo newlinecyclodehydration in the presence of T3P to yield 2-amino substituted 1,3-benzothiazines newlineand on the other hand molecular iodine facilitates desulfurization of the thiourea to yield 2-amino substituted 1,3-benzoxazines. 2-amino substituted 1,3-benzothiazinones were synthesized by reacting anthranilic acids and isothiocyanates in the presence of EDC.HCl. 2-aryl substituted 1,3-benzothiazinones were synthesized by employing thiobenzamides in the presence of T3P. All the compounds synthesized were characterized by 1HNMR, 13C, Mass spectroscopic (LCMS, HRMS) analysis. Docking studies against TANKYRASE-1 enzyme for colorectal cancer (CRC) and antibacterial studies were also discussed.