SYNTHESIS AND BIOLOGICAL STUDIES ON SOME HETEROATOM CONTAINING MOLECULES AND PHYTOCHEMICAL INVESTIGATION ON SALSOLA FOETIDA

Abstract

This dissertation comprises of two parts. The part-A describes the synthesis and biological studies on some heteroatom containing molecules through improved methodologies in organic synthesis. The part-B describes the isolation and structural characterization of secondary metabolites from, Salsola foetida Linn Part-A This part describes the synthesis and biological studies on some heteroatom containing molecules. The work embodied in this part has been divided into chapters. Chapter-A: The work reported in this chapter deals with a modified, economical and efficient synthesis of various pyrazolo[4,3-d]pyrimidin-7-ones; sildenafil (Viagra®) and its analogues possessing enzyme inhibitory activities. Additionally, a series of new methyl ether derivatives of sildenafil (Viagra®) possessing very interesting tyrosinase inhibitory potential were also synthesized. A brief structure-activity relationship (SAR) is discussed in this chapter Chapter-2: This chapter describes the synthesis of a variety of tetraketones with variable substituents at C-7 and were evaluated as tyrosinase inhibitors. This series of tetraketones molecules are found to be good inhibitors for the tyrosinase enzyme. Remarkably, compounds 50 (IC50=2.06μM), 36 (IC50=2.09μM), 41 (IC50=2.61μM), and 52 (IC50=3.19μM), were found to be the most active compounds of the series, which are even more potent than the standard drugs, kojic acid (IC50=16.67μM), and L-mimosine (IC50=3.68μM). This study may lead to the discovery of some lead compounds for the management of a number of dermatological disorders including hyper-pigmentation, as well as for the treatment of skin melanoma Chapter-3: In this chapter a new method for the esterification of aromatic carboxylic acids by substituted toluenes in a mixture of sodium bromate and sodium hydrogen sulfite in a two-phase system is described Phytochemical investigations on the air-dried whole plant Salsola foetida resulted in the isolation and structural determination of three new compounds, 3-(4””-dimethoxyphenyl)-N-[2’-(3”,4”-dihydroxyphenyl)-2’-hydroxyethyl]acrylamide (37), 3-(3””,4””-dimethoxy-phenyl)-N-[2’-(3”-4”-dihydroxyphenyl)-2’-hydroxyethl]acrylamide 39). Eight known compounds namely Stigmasterol (43), β-Sitosterol (44), Isoscopoletin (45), Scopoletin (46), Daphnoretin (47), 3-({6-[(β-D-glucopyranosyl)oxy]-2-oxo-2H-1-benzopyran-7-yl}oxy)-7-methoxy-2H-1-benzopyran-2-one (48), Bergaptol (49), Bergaptol-O-β-D-glucopyranoside (50) were also isolated for the first time from Salsola foetida. The structure elucidations of these compounds were carried out with the help of modern spectroscopic techniques. Compounds 37-39 exhibited potent tyrosinase inhibitory and antioxidant activities. Helv. Chim. Acta 2003, 86, 457. Helv. Chim. Acta 2003, 86, 457. Helv. Chim. Acta 2003, 86, 457