I= STUDIES ON THE CHEMICAL CONSTITUENTS OF TARAXACUM WALLICHII, SALVIA CABULICA AND SYNTHESIS OF THE ANALOGUES OF DEPSIPEPTIDE JASPLAKINOLIDE
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Title of Thesis
STUDIES ON THE CHEMICAL CONSTITUENTS OF TARAXACUM WALLICHII, SALVIA CABULICA AND SYNTHESIS OF THE ANALOGUES OF DEPSIPEPTIDE JASPLAKINOLIDE

Author(s)
Shazia Yasmeen
Institute/University/Department Details
H.E.J Research Institute of Chemistry/ University of Karachi
Session
2006
Subject
Chemistry
Number of Pages
222
Keywords (Extracted from title, table of contents and abstract of thesis)
taraxacum wallichii, salvia cabulica, depsipeptide jasplakinolide, asteraceae, lamiaceae, amino acid, cyclodepsipeptide

Abstract
The work embodied in this thesis is divided into two parts. Part-A describes the studies of the chemical constituents of Taraxacum wallichii DC. (Asteraceae) and Salvia cabulica Bth. (Lamiaceae). Part-B deals with the synthesis of analogues of jasplakinolide which is a 19-membered cyclic depsipeptide showing potent insecticidal, anitifungal and cytotoxic activity.

Part A: The phytochemical investigations on T. wallichii DC. resulted in the isolation and characterization of a new guaianolide taraxacin (44), the structure of which was confirmed by single crystal X-ray diffraction technique.

-----------------------------------------Taraxacin( Snap) ----------------------------------

The following known compounds were also isolated from T. wallichii. 1. Ketolactone (45) 2. β-Sitosterol (46) 3. Oleanolic acid (47) 4. β -Sitosterol 3-0- β -D-glucopyranoside (48)

The work on Salvia cabulica Bth. resulted in the isolation and characterization of following five known compounds.

1. Tetracosanoic acid, 2-( 4-hydroxyphenyl)ethyl ester (49) 2. Lupeol (50) 3. β -Sitosterol (49) 4. Oleanolic acid (47) 5. β -Sitosterol β -0- β -D-glucopyranoside (48)

Part B : This part describes the synthesis of the analogues (Sy2741) and (Sy5141) of depsipeptide jasplakinolide. While several methods for the synthesis of p-amino acid exist, synthesis of four analogues of p-tyrosine derivative 72 (a-d) was effectively achieved using Evans methodology.

------------------------ β-Tyrosine derivative analogues(Snap)----------------------------

72(a) was incorporated in tripeptide fragments (81, 93 and 100), using DCC/HOBT as the coupling reagent, whereas the known tripeptide 107 was synthesized according to the literature.

-------------------------------Tripeptide fragments(Snap)-----------------------------------------

The tripeptides 81 and 93 were incorporated in macrocycles Sy2741 and Sy5141. Final macrolactam formation was achieved using TB TU in the presence of HOBT.

-----------------------------Jasplakinolide Analogues(Snap)--------------------------------------

Conformational analyses of theses synthetic analogues showed that the macrocyclic rings are more rigid than the jasplakinolide ring but all in all their conformations are very well comparable to the natural product. These analogues were tested for cytotixicity against two cell lines, L929 mouse fibroblast and ovary cancer cell line SKOV-3. Compound Sy5141 turned out to be most active among the two.

Download Full Thesis
4412.81 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
377.46 KB
2 1 Parat- A : General Introduction 2
1270.27 KB
  1.1 Biosynthesis And Biogenesis 4
  1.2 Taraxacum 23
  1.3 Results And Discussion 31
  1.4 Experimental 37
  1.5 Salvia Cabulica 46
  1.6 Results And Discussion 50
  1.7 Experimental 54
  1.8 References 58
3 2 Part- B : Amide Forming Reactions 65
3033.64 KB
  2.1 ’-Amino Acid-Derivative 80
  2.2 Cyclodepsipeptide 85
  2.3 Results And Discussion 93
  2.4 Experimental 140
  2.5 References 197
  2.6 Supporting Information 200