SYNTHESIS OF BENZOFUSED NITROGEN BASED HETEROCYCLES

The diversity in structure and the biological activities of N containing heterocycles make them no doubt important substrates. Work presented here reflects our studies towards synthesis of a variety of five, six and seven membered heterocycles fused with a benzene ring. Due to their well established biological activity profile, special emphasis has been placed on the synthesis of indoles, benzoxazepines and benzodiazepines. The asymmetric synthesis of benzodiazepines (308-310) & novel (3R)-4,1-benzoxazepines2,5-diones (336-339) has been achieved employing chiral pool methodology that involved coupling of readily available amino acids / ?-haloacid halides (285, 325-327) (that served as asymmetric precursors) with substituted anthranilic acid as symmetric precursors. We have reported the use of (S)-2-bromopropanoic acid that favours a single step synthesis of 4,1benzoxazepines-2,5-diones with low ee whilst, the use of (S)-2-chloroacids (322-324) yielded novel (S)-N-acylanthranilic acids (328-334) exclusively. Conversion of these acids (328-334) to the corresponding chiral 4,1-benzoxazepines-2,5-diones (336-339) was achieved in a subsequent cyclization step in high ee along with the formation of a side-product 335a-b (3,1-benzoxazine-4-one). The condensation of formylated indoles (364-365) with a variety of anilines bestowed a series of novel indole imines (383-404), which upon reduction rendered a series of novel indole amines (405-413). The complexation of synthesized novel indole imines with Cu2+ and Zn2+ furnished a series of new metal inserted six membered bis-indoles (415-424), reflecting their extraordinary potential to bind with different metals. Some imines and their corresponding Cu2+ & Zn2+ complexes were randomly selected and evaluated for antibacterial, anti-inflammatory and antioxidant activities. A few of the candidates exhibited promising results. The structure activity relationship (SAR) of the candidates has been discussed as well