First Total Synthesis of 3 4 7_Trimethoxy 9 10 Dihydrophenanthrene 1 5_Diol and Development of Novel Synthetic Methodologies with their Anticancer Evaluation

Abstract

The thesis entitled First Total Synthesis of 3,4,7-trimethoxy-9,10-dihydrophenanthrene-1,5-diol and Development of Novel Synthetic Methodologies with Their Anticancer Evaluation has been divided into five chapters. newlineCHAPTER-1 newline newlineThis chapter consists of overview of natural products. Structural characteristics of phenanthrenes, general methods for the synthesis of 9,10-dihydrophenanthrenes and their biological activities. Introduction of spirocyclohexaneindene-2,5-dienes derivatives and their biological activities and introduction of Quinoline consists of 1H-1,2,3-triazole derivatives with their biological activities were explained in detail. newlineCHAPTER-2 newline newlineIn this chapter, all the attempted methods to synthesize the 3,4,7-Trimethoxy-9,10- dihydrophenanthrene-1,5-diol was explained in detail. The key features of our synthetic approach are Perkin condensation, followed by bromination, palladium mediated intramolecular C-C bond coupling, and selective isopropyl ether cleavage. All thesynthesized compounds are purified and characterized by IR, 1H NMR, 13C NMR and HRMS/LC-MS. After several attempts, the key Pd- mediated cyclization allowed bromo precursor to construct phenanthrene scaffold in high yield and with a high regio-control. newlineCHAPTER-3 newline newlineThis chapter represents the short and efficient route for the construction of relatively challenging Spiro indene dienone acid via a key step involving Lewis acid in the formation of Spiro skeleton. A series of spirocyclohexaneindene-2,5-diene derivatives were synthesized from Spiro-Acid which in turn was prepared from the easily accessible starting materials. The structure of spiroester was thoroughly further confirmed by 2DNMR analysis The synthesized compounds were screened for anticancer activity using murine melanoma cell line (B16F10), human breast cancer cell line (MCF- 7) and human non-small cell lung carcinoma cell lines (A549). Among them 7f (tri fluorobenzene) newline newlineand 7g (di fluorobenzene) analogues were the most active compounds in all three cell lines in the series. newline