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Title of Thesis

Naheed Kausar
Institute/University/Department Details
Department of Chemistry/ University of Karachi
Number of Pages
Keywords (Extracted from title, table of contents and abstract of thesis)
chirality, metal complexes, stereo selectivity, asymmetric conjugate addition reactions, chiral ligands

One of the greatest challenges of modern day synthesis is the multiplication of chirality in the laboratory. In nature this is achieved through enzymatic processes and in laboratory syntheses the scalemic (synonymous with aracemic or nonracemic ) transition metal complexes used in substoichiometeric or catalytic amounts have served a templates in asymmetric reactions.

We developed a new class of scalemic amino thiolatocopper (I) complexes for conjugate addition reactions. Conjugate addition of organocopper reagents to α ,β- unsaturated compounds is one of the most reliable carbon-carbon bond forming reaction. The importance of this reaction has prompted numerous searches for procedures and methods to effect the conjugate addition process with asymmetric induction.

A new class of amino thiolatocopper (I) complexes is derived from derivatives of L-cysteine. It belongs to sulfur containing class of amino acid and is capable forming a large variety of derivatives. The following chiral ligands were synthesized starting L-cysteine.

S- methyl L-cysteine 1; S,N,N-trimethyl L-cysteine 2; 2-dimethylamino-3methylthio propanol 3; 2-dimethylamino-3methylthyio methoxypropane 4; 2-dimethylamino-3-methylthio ethoxypropane 5; S-ethyl L-cysteine 6; N, N-dimethyl S-ethyl L-cysteine 7; 2-dimethylamino-3ethylthio propanol 8; 2-dimethylamino-3-ethylthio methoxypropane 9; 2-dimethylamino-3ethylthio ethoxypropane 10; N,N-dimethyl L-cysteine 11; 2-dimethylamino-3-thio propanol 12; 2-dimethylamino-3-thio methoxypropane 13 and 2-dimethylamino-3-thio ethoxypropane 14.

The series of chiral ligands 1-14 have been examined as a non-transferable chiral ligand of Cu(I) complex during asymmetric conjugate addition reaction. Copper complex which is formed in situ efficiently transferred their chiral activity to α ,β- unsaturated substrate. 2-Cyclohexenone, methyl crotonate or methyl cinnamate used as prochiral substrate and transferable moiety of the complexes were butyl, pentyl or vinyl.

The different of induction depends on many factors such as solvent, added salts, stoichiometry of reagents, presence of salts or additives temperature, addition method, quality of reagents etc. a few factor are investigated for improvements of optical yields of products.

Thiourea is the standard inhibitor of urease, which covalently modifies cysteine residues of the urease. We supposed that our synthesized derivatives also act as inhibitors. Therefore the compounds 1-14 were primarily screened for inhibition of urease. Almost all compounds, which were tested, showed good results against urease from Bacillus pasteurii. The same concentration of compounds 1-3, 6-8, 11 and 12 were used for inhibition of protease. Only 11 and 12 were found to be effective inhibitors against protease of trypsin and of papain.

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2622.27 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
163.97 KB
2 1 Summary 1
25.17 KB
3 2 Introduction 3
616.95 KB
  2.1 EPC-synthesis, asymmetric synthesis 4
  2.2 Stereoselectivity 8
  2.3 Meaures of stereoselectivity 12
  2.4 Asymmetric conjugate addition reactions 16
4 3 Results and Discussion 71
268.18 KB
  3.1 Syntheses of chiral ligands 71
  3.2 Multiplicity of chirality by using scalemic amino thioloato -copper (I) complexes 86
  3.3 Biological activities of compounds 100
5 4 Proposed future research plans 103
29.27 KB
  4.1 Part-I 103
  4.2 Part-II 104
6 5 Experimental section 106
287.3 KB
  5.1 General procedures 106
  5.2 Syntheses of chiral ligands 116
  5.3 Chiral induction to α ,β - unsaturated substrates 135
  5.4 Biological activities of chiral ligands 139
7 6 References and notes 141
144.52 KB
8 7 Presentations and publications 154
27.17 KB