I= ISOLATION AND STRUCTURE ELUCIDATION STUDIES IN THE CHEMICAL CONSTITUENTS OF THEVETIA NERIFOLIA JUSS AND POTENTIAL BIOLOGICALLY SIGNIFICATION DERIVATIVES OF ALKYL AND ARYL OXYGEN COMPOUNDS
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Title of Thesis
ISOLATION AND STRUCTURE ELUCIDATION STUDIES IN THE CHEMICAL CONSTITUENTS OF THEVETIA NERIFOLIA JUSS AND POTENTIAL BIOLOGICALLY SIGNIFICATION DERIVATIVES OF ALKYL AND ARYL OXYGEN COMPOUNDS

Author(s)
Qyyum Adil
Institute/University/Department Details
H.E.J. Research Institute Of Chemistry/ University Of Karachi
Session
1994
Subject
Chemistry
Number of Pages
229
Keywords (Extracted from title, table of contents and abstract of thesis)
thevetia nerifolia juss, alkyl oxygen compounds, aryl oxygen compounds, terpenoids, steroids, cardiac glycosides, alkyl constituents, ursane, catechol

Abstract
The work embodied in the present thesis is presented in two. parts. Part A describes the isolation and structure elucidation studies in the chemical constituents of Thevetia neriifolia and part B deals with the potential biologically significant derivatives of alkyl and aryl oxygen compounds. A brief review of the biosynthesis of terpenoids, steroids and cardiac glycosides is also included.

PART-A The introduction of part A provides a review of the earlier contributions made in the chemistry and pharmacology of the plant Thevetia neriifolia and a brief account of the present work.

Studies in the chemical constituents of T. neriifolia have resulted in the isolation and structure elucidation of 14 compounds including 3 new (3,12,14) and 11 known (1,2,4-11,13) constituents listed below. The known compounds are reported for the first time from this source.

i.Oleanolic acid (1) ii.Ursolic acid (2) iii.Neriifoside (3) iv.peruvoside (4) v.α-Amyrin (5) vi.β-Amyrin (6) vii.Lupo/ acetate (7) viii12β-Hydroxy-4, 16-pregna-dien-3, 20-diane (8) ix.Neolupenyl acetate (9) x.β-Sitosterol (10) iii3 β -Hydroxy-stigmast-5-en-7-one (11) iv3 β -Hydroxy-11a, 12a-er:oxyurs-3 β,28-0Iide (12) v.3 β -Hydroxy-11-oxours-12-er -2B-oic; acid (13) vi.3 β -O-(a-L - Thevetose)-3 β, 14 β.c!ihdiroxy-14 (13-- > 12)abeo-5 β, 12 β, 14 β * carda-13(18),20(22)-dienolide (14)

In one working the metabolic extract of Thevetia neriifolia leaves were tested for its effect on blood pressure in normotensive anaesthetized rats and was found hypertensive at 48-72 mg/kg. However on, further fractionation a variety of activities (hypertensive, hypotensive and biphasic) was observed in various fractions. Thus it was noted that the main aqueous phase possesses hypertensive activity although now at a lesser dose i.e. 10-30 mg/kg while the ethyl acet3te phase showed hypotensive effect at a nose of 5-20 mg/kg. The latter was subjected to further separation as described in the experimental (scheme-iv) and the pure compounds (1-14) ultimately obtained were also determined for their activity and the results are presented in Table-2. The cardio-vascular activity was determined by Dr. Anwar H. Gilani of Agha Khan Medical University and his co-workers and the details will be published by them.

PART - B This part of the thesis deals with the chemistry of potential biologically significant derivatives of ursane and catechol series. As a result synthesis of eighteen derivatives of ursane series and thirty eight derivatives of catechol series has been achieved. In the ursane series noted below ten compounds (2-5,18,19, 21,23,25,26) are new, while the rest have been reported earlier

i.Methyl 3 p-acetoxy-11.oxours-12 p, 13 β -epoxy-28-oate (2) ii.Methyl 3 β -acetoxy-11-oxours-12-en-28-oate (3)

*This compound has been published in J Net Prod, 56 (4),613 (1993). It was presented in the Fifth International Symposium on Natural Product Chemistry held in Karachi, Pakistan, Jan. 5-9,1992. However,

iii.3 β -Acetoxy-'f1-oxours-12-en-28-oic acid (4) .iv.Methyl 3 β -acetoxyurs-12-en-15a-hydroxy-28-oate (5) v.3f3-Acetoxy-11a, 12a-epoxyurs-13 (β,28-olide (6) vi.Methyl 3 β -acetoxy-11-oxours-12, 15-dien-28-oate (7) vii.3- β xours-11-en-28-oic acid (17) viii3-0xours-1, 12-dien-28-oic acid (18) ix.2,3-Dioxours-12-en-28-oic acid (19) x.2-Hydroxy-3-oxours-1, 12-dien-28-oic acid (20) xi.3-0xours-9(11), 12-dien-28-oic acid (21) xii.2 β,3 β -Dihydroxyurs-12-en-28-oic acid (22) xiii.3 β -Hydroxyurs-1, 12-dien-28-oic acid (23) xiv.3 β -Hydroxyurs-12-en-:!8-oic acid (24) xv.3-0xours-11-en-13 β,28-oiiue (25) xvi.3, 11-Dioxours-12.en-28-oic acir' (26) xvii.3 β -Hydroxyurs-11-en-13 β,28-olide (27) xviii.3 {J-Acetoxyurs-11-en-13 (J,28-0Iide (28) In the thirty eight derivatives (2-39)01 the catechol series listed below thirty four compounds (2-13,15-19,21-28,30,31,33-39) are new i.4-Benzyl catechol (2) ii.4,5-Dibenzyl catechol (3) iii.3,4,5,6-Tetrabenzyl catechol (4) iv4-Nonyl catechol (5) v4,S-Dinonyl catechol (6) vi3,4,S,ti-Tetranonyl catechol (7) vii4-(2-0ctyl) catechol (8) viii4,S-Di-(2-octyl) catechol (9) ix3,4,5,6-Tetra-(2-octyl) catechol (10) x4-(3-0ctyl) catechol (11) x4,5-Di-(3-octyl) catechol (12) xii3,4,S, 6- Tetra-(3-octyl) catechol (13) xiii4-Heptyl catechol (14) xiv4,S-Diheptyl catechol (15) xv3,4, S, 6-Tetraheptyl catechol (16) xvi4-(2-Heptyl) catechol (17) xvii4,5-Di-(2-heptyl) catechol (18) xviii3,4,S,6-Tetra-(2-heptyl} catechol (19) xix4-Hexyl catechol (20) xx,S-Dihexyl catechol (21) xxi3,4,5,6-Tetrahexyl catechol (22) xxii4-(2-Hexyl) catechol (23) xxiii4,5-Di-(2hexyl) catechol(24) xxiv4-(3-Hexyl) catechol (26: xxv4,S-Di-(3-hexyl) catechol (27) xxvi3,4,5,6-Tetra-(3-hexyl) catechol (28) xxvii4-Pentyl catechol (29) xxviii4,S-Dipentyl catechol (30) xxix3,4,5, 6- Tetraheptyl catechol (31) xxx4-Butyl catechol (32) xxxi4,S-Dibutyl catechol (33) xxxii3,4,S,6-Tetrabutyl catechol (34) xxxiii4-Propyl catechol (35) xxxiv4,5-Dipropyl catechol (36) xxxv3,4,S,6- Tetraheptyl catechol (37) xxxvi4-Etl7yl catechol (38) xxxvii4-Methyl catechol (39)

Antibacterial activity of these derivatives was determined by microbiologists collaborating with us and the details will be published by them. The cytotoxicity of these compounds was investigated by brine shrimp method. The activities have been briefly discussed with reference to the number and position of the alkyl constituents.

Extensive spectroscopic techniques such as ElMS, FDMS, UV, IR, 1H_ and 13C_NMR (BB,DEPT), 2D-NMH (COSY-45,NOESY, Hetero-COSY, J-resolved) and chemical reactions were employed to elucidate the structures of the compounds noted in part A and B.

The work embodied in the present thesis has resulted in thirteen research papers as listed in the list of publications

Download Full Thesis
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S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
33.66 KB
2 1 Summary 1
47.08 KB
3 2 General Introduction 8
45.01 KB
4 3 Biosynthesis 13
45 KB
5 4 Introduction 49
177.33 KB
6 5 Discussion 76
69.7 KB
7 6 Experimental 85
176.16 KB
8 7 Reference 108
62.75 KB
9 8 Derivatives Of Ursane Series 119
21.01 KB
  8.1 Introduction 121
10 9 Discussion 145
152.69 KB
11 10 Experimental 145
165.24 KB
12 11 References 167
42.03 KB
13 12 Derivatives Of Catechol Series 174
22.04 KB
  12.1 Introduction 174
14 13 Discussion 177
120.56 KB
15 14 Experimental 190
180.76 KB
16 15 References 214
19.06 KB
17 16 Appendix 218-229
71.45 KB