I= SYNTHESIS AND BIOLOGICAL STUDIES ON SOME HETEROATOM CONTAINING MOLECULES AND PHYTOCHEMICAL INVESTIGATION ON SALSOLA FOETIDA
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Title of Thesis
SYNTHESIS AND BIOLOGICAL STUDIES ON SOME HETEROATOM CONTAINING MOLECULES AND PHYTOCHEMICAL INVESTIGATION ON SALSOLA FOETIDA

Author(s)
Ghulam Murtaza Maharvi
Institute/University/Department Details
University of Karachi/ H.E.J. Research Institute of Chemistry
Session
2004
Subject
Chemistry
Number of Pages
190
Keywords (Extracted from title, table of contents and abstract of thesis)
heteroatom, salsola foetida, tetraketones, tyrosinase, toluenes, aromatic carboxylic acids, sildenafil citrate, cinnamic acids, noradrenaline, chenopodiaceae, salsola linn

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

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S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents 0
193.85 KB
2 1 Part-A: A Modified, Economical And Efficient Synthesis Of Various Pyrazolo [4,3-D] Pyrimidin-7-Ones; Sildenafil (Viagra®) And Its Analogues Possessing Enzyme Inhibitory Potential 1
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  1.1 Summary Of Capter-1 1
  1.2 General Introduction 2
  1.3 Drug Development 2
  1.4 Organic Synthesis 2
  1.5 Microwaves-Assisted Synthesis 3
  1.6 Applications Of Microwaves In Organic Synthesis 7
  1.7 Pyrazolo[4,3-D]Pyrimidine-7-Ones 12
  1.8 Sildenafil Citrate (Viagra®) 16
  1.9 Tyrosinase Enzyme 21
  1.10 Results And Discussion Of Chapter-1 23
  1.11 Chemistry 23
  1.12 Synthesis Of Methyl-Ether Derivative Of Compound 74 32
  1.13 Biological Studies 37
  1.14 Experimental 43
  1.15 General Experimental 43
  1.16 Ethyl-2,4-Dioxoheptanoate (31) 43
  1.17 Ethyl-5-Propyl-2h-Pyrazole-3-Carboxylate (32) 44
  1.18 1-Methyl-3-Propyl-5-Pyrazolecarboxylic Acid (33) 44
  1.19 4-Bromo-1-Methyl-3-Propyl-1h-Pyrazole-5-Carboxylic Acid (34) 45
  1.20 4-Bromo-1-Methyl-3-Propyl-1h-Pyrazole-5-Carboxylic Acid (35) 45
  1.21 General Procedure For The Synthesis Of Compounds 49-61 And Compounds 62-74 46
  1.22 5-(2-Ethoxy-5-Chlorosulfonylphenyl)-1-Methyl-3-Propyl-1,6-Dihydro-7h-Pyrazolo-[4,3-D]Pyrimidin-7-One (81) 55
  1.23 General Procedure For The Preparation Of Compounds 92-101 56
  1.24 Synthesis Of 5-(2-Ethoxyphenyl)-1-Methyl-3-Propyl-1h-Pyrazolo-[4,3-D]Pyramid-Ine-7-Yl Methyl Ether (102) 61
  1.25 5-(2-Ethoxy-5-Chlorosulfonylphenyl)-1,6-Dihydro-1h-Pyrazolo-[4,3-D]Pyramid-Ine-7-One (103) 61
  1.26 5-(2-Ethoxy-5-Chlorosulfonylphenyl)-1,6-Dihydro-3—Propyl-1,6dihyro-1h-Pyrazolo-[4,3-D]Pyramid-Ine-7-Yl Methyl Ether (104) 62
  1.27 General Procedure For The Preparation Of Compounds 105-114 62
  1.28 Tyrosinase Inhibition Assay 67
  1.29 References 68
  1.30 Synthesis And Structure-Activity Relationship ( Sar ) Of Tetraketones For Tyrosinase Inhibition 74
  1.31 Summary 74
  1.32 General Introduction 74
  1.33 Results And Discussion Of Chapter-2 77
  1.34 Chemistry 77
  1.35 Biology 79
  1.36 Experimental 85
  1.37 General Procedure For The Preparation Of Compounds 27-55 85
  1.38 References 94
  1.39 An Expedient Esterification Of Aromatic Carboxylic Acids Using Sodium Bromate And Sodium Hydrogen Sulfite 97
  1.40 Summary Of Chapter 3 97
  1.41 General Introduction 98
  1.42 Results And Discussion Of Chapter-3 102
  1.43 Experimental 107
  1.44 General Procedure For The Preparation Of 23-42 107
  1.45 References 11 3
3 2 Part-B: Introduction 117
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  2.1 General Introduction 117
  2.2 Cinnamic Acids 122
  2.3 Noradrenaline 126
  2.4 Chenopodiaceae 127
  2.5 Salsola Linn 127
  2.6 Phytochemical Studies On Salsola Foetida 131
  2.7 Salsola Foetida Linnaeus 131
  2.8 Bioactivity Of Salsola Foetida 132
  2.9 New Compounds Isolated From Salsola Foetida 133
  2.10 Structure-Activity Relationship 158
  2.11 Conclusion 160
  2.12 Known Compounds Isolated From Salsola Foetida 161
  2.13 Experimental 169
  2.14 General Procedure 169
  2.15 Plant Material 170
  2.16 Extraction And Isolation 170
  2.17 Determination Of Stereochemistry By Horeau’s Procedure 181
  2.18 Determination Of Biological Activities 181
  2.19 References 185