I= STUDIES IN THE CHEMICAL CONSTITUENTS OF MORINGA OLEIFERA LAM AND PREPARATION OF POTENTIAL BIOLOGICALLY SIGNFICANT DERIVATIVES OF 8-HYDROXYQUINOLINE
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Title of Thesis
STUDIES IN THE CHEMICAL CONSTITUENTS OF MORINGA OLEIFERA LAM AND PREPARATION OF POTENTIAL BIOLOGICALLY SIGNFICANT DERIVATIVES OF 8-HYDROXYQUINOLINE

Author(s)
Rubeena Saleem
Institute/University/Department Details
University of Karachi/ H.E.J Research Institute of Chemistry
Session
1995
Subject
Chemistry
Number of Pages
357
Keywords (Extracted from title, table of contents and abstract of thesis)
moringa oleifera lam, 8-hydroxyquinoline, glucosinolates, aromatic compounds, fattyacids

Abstract
The work embodied in this thesis consists of two parts. Part A describes the bioassay directed isolation and structure elucidation studies in the chemical constituents of Moringa oleifera leaves ad pods, and Part B deals with the preparation of 8-hydroxyquinoline derivatives and evaluation of their biological activities. A brief review on the biosynthesis of glucosinolates, aromatic compounds and fatty acids is also included.

Part A

This part provides a review of the earlier contributions made in the chemistry, pharmacology, edible and water coagulation properties of the genus Moringa and a brief account of present work including a bioassay directed fractionation and isolation of a number of constituents including novel glycosides possessing hypotensive activity from the leaves and pods of Moringa oleifera. Investigation on the ethanolic extract of M.oleifera leaves has resulted in the isolation and structure elucidation of twenty three (23) compounds, twenty (20) of which are new and three (22, 23, 24) are known constituents. They are listed below:

Niaziminin A (1) Niaziminin B (2) 4-(2’,3’,4’-Tri-Oacetyl-a-L-rhamnosyloxy) benzyl nitrile (3) Niazicinin A (4) Methyl-4-(2’,3’,4’-tri-O-acetyl-a-L-rhamnosyloxy) benzyl carbamate (E) (5) Methyl-4-(2’,3’,4’-tri-O-acetyl-a-L-rhamnosyloxy) benzyl thiocarbamate (E) (6) Methyl-4-(2’,3’,4’-tri-O-acetyl-a-L-rhamnosyloxy) benzyl thiocarbamate (Z) (7) Methyl-4-(2’,3’,4’-tri-O-acetyl-a-L-rhamnosyloxy) benzyl carbamate (Z) (8) Niazimicin B (9) Ethyl-4-(2’,3’,4’-tri-O-acetyl-a-L-rhamnosyloxy) benzyl carbamate (E) (10) Niazicin B (11) O-Ethyl-4 (2’,3’,4’-tri-O-acetyl-a-L-rhamnosyloxy) benzy1 thiocarbamate (Z) (12) Niazinin B(13) Niazimicin A(14) Niazinin A(15) Niazirinin (16) NiaziminB (17) 4 (4’-O-Acetyl-a-L-rhamnosyloxy) benzaldehyde (18) Niazimin A (19) Niazicin A (20) 4-(4’-O-Acetyl-a-Lrhamnosyloxy) benzyl isothiocyanate (22) Niazirin (23) 4-(a-L-Rhamnosyloxy) benzyl isthiocyanate (24)

Bioassay guided fractionation of the ethanolic extract of M. Oleifera pods afforded a number of fractions. Flash column chromatography (FCC) of the petroleum ether soluble fraction (APES) of the acidic fraction gave three pure compounds (77, 78 and 79) along with β-sitosterol. Compounds 78 and 79 are new constituents. Compound 77 and β-sitosterol possess hypotensive activity. GC and GCMS of the remaining fractions of FCC led to the identification of sixty three (63) constituents, seventeen (17) of which (43,46,48,49,59,61,65,66,68,72,74,76,83, and 89 and 90) are new. All the compounds isolated/detected from the fraction APES of pods are listed below:

Pentacosane (26) Heptacosane (27) Nonacosane (28) Sulfur (S8) Methyl hexadecanoate (29) Ethyl pentadecanoate (30) Ethyl hexadecanoate (31) Ethyl heptadecanoate (32) Methyl octadecanoate (3) Ethyl octadecanoate (34) Ethyl eicosanoae (35) Ethyl docosanoate (36) Ethyl 9-octadecenoate (37) Ethyl tricosanoate (38) Ethyl-9-hexadecenoate (39) Methyl octadeca-9, 12-dienoate (40) Ethyl heptadeca-9, 12-dienoate (41) Ethyl 9-nonadecenoate (42) 9-Methyl octadecane nitrile (43) Isothiocyanato-4-hexenoic acid (44) Isothiocyanato-3-pentenoic acid (45) 7-(p-Hydroxy) phenoxy heptanoic acid (46) (p-Hydroxy) Phenoxy acetic acid (47) 4-(p-Hydroxy) Phenyl ethylbutanoate (48) Isothiocyanato hexanoic acid (49) Octadecanoic acid (50) Eicosanoic acid (51) Tetracosanoic acid (52) β-Sitosterol Propyl-p-hydroxy benzoate (53) Heptadecadien – 2 one (54) 6-Methyl docosane (55) Ethyl octadeca-9,12-dienoate (56) Docoasen-8-ol (57) p-Hydroxyphenyl methoxyethance (58) 6, 9-Dimethyl dodecanoic acid (59) 8-Heptadecanol (60) 8-Nonadecanol (61) 9-Methyl pentadecene isothiocyanate (62) Hexadecanoic acid (63) 6-Methyl eicosane (64) 1-Ethoxytricontane (65) 1-Ethoxyheptadecane (66) Heptadecane nitrile (67) 10-Methyl nonadecane isocyanate (68) Tridecene (69) p-Hydroxybenzoic acid (70) 9-Octadecenoic acid (71) 4, 10-Dimethyl-13-nonacosanol (72) Docosanoic acid (73) 15-Cyano-2-methyl pentadecanoic acid (74) 9, 12-Octadecadienoic acid (75) 4,11-Dimethyl-12-docosanol(76) Methyl p-hydroxybenzoate (77) 11-Cabonyl-12, 16-dioxo-14-hydroxy-18-tricoasene (78) Ethy1-4(a-L-rhamnosyloxy) benzyl carbamate (79) p-Hydroxybenzyl ethyl carbamate (80) Tetradecanoic acid (81) Heptadecanoic acid (82) Dodecanyl isothiocyanate (83) 9-Methyl-eicoasen-1, 11-diol (84) p-Aminobenzaldehyde (85) p-Hydroxyphenyl acetonitrile (86) 2-Octadecanone (87) Methyl 9-octadecenoate (88) Tetradecanyl isothiocyanate (89) 1-Ethoxypentadecane (90)

Bioassay guided fractionation of the neutral petroleum ether insoluble fraction (NPE1) of the ethanolic extract of M.oleifera pods employing vacuum liquid chromatography (VLC), GC and GCMS techniques have resulted in the isolation/detection and identification of the following compounds, fourteen (14) of these (1, 2, 6, 13-15, 93-98, 100 and 101) are new. Glycosides 1, 2, 6, 13-15 and 24 have been found to be the hypotensie principles f the pods as in case of the leaves.

Heptadecane isocyanate (91) Octadecane isocyanate (92) Tricosane isothiocyanate (93) Henicosane carbamic acid (94) 4,5-Dimethyl decane (95) Ethyl-14-henicosenoate (96) Methyl-15-cyano-pentadecanoate (97) Methyl-1amino-pentasulfide-5-sulfinate (98) Tricosane (99) O-Ethy1-4-hydroxybenzyl thiocarbamate (100) Niaziminin A (1) Niaziminin B(2) O-Methyl-4(2’,3’,4’-tri-O-acetyl-a-L-rhamnosyloxy) benzyl thiocarbamate (E) (6) Niazinin A (15) Niazinin B (13) Niazimicin A (14) 4-(a-L-Rhamnosyloxy) benzylisothiocyanae (24) Niazidin (101)

Part - B

This part of the thesis deals with the chemistry of potential biologically significant derivatives of 8-hydroxyquinolineemploying simple reactions and Mannich reaction. As a result, preparation of twenty one (21) new (2-8, 10-13, 16-18, 22-24, 32-34 and 36) derivatives has been achieved. Most of these compounds were found promising antibacterial, antifungal, antiplatelet aggregating, cytotoxic and analgesic agents. List of the compounds prepared is as follows.

Mannich Reaction Products

7-[a-(3”, 4”-Dichloroanilino) benzyl]-8-hydroxyquinoline (2) 7-[a-(N-Acetyl-3”,4”-Dichloroanilino) benzyl]-8-hydroxyquinoline (3) 7-[a-(N-Formyl-3”,4”-Dichloroanilino) benzyl]-8-hydroxyquinoline (4) 7-[a-(N-Benzoyl-3”,4”-Dichloroanilino) benzyl]-8-hydroxyquinoline (5) 8-Oxy-[a-(3”,4” Dichloroanilino) benzyl]-quinoline (6) 7-[a-(3”,4”-Dichloroanilino)-3’-nitrobenzyl]-8-hydroxyquinoline (7) 7-[a-(N-Acetyl-3”,4”-Dichloroanilino)-3’-nitrobenzyl]-8-hydroxyquinoline (8) 7-[a-(Anilino) benzyl]-8-hydroxyquinoline (9) 7-[a-(N-Acetyl anilino) benzyl]-8-acetoxyquinoline (10) 7-[a-(N,N-Dimethyl aniline)-benzyl]-8-hydroxyquinolinium iodide (11) 7-(a-3’-Nitrobenzyl)-bis-8-hydroxyquinoline (12) 7-(a-3’-Nitrobenzyl)-bis-8-methoxyquinoline(13) 2,6-Dichloro-N-(3’-nitrobenzylidene) aniline (16) 2,6-Dichloro-N-(a-hydroxy-3’-nitrobenzyl) aniline (17) 7-(a-Hydroxy-3’-nitrobenzyl)-8-hydroxquinoline (18) 7-(a-Ethoxybenzyl)-8-hydroxquinoline (20) 7-(a-Hydroxybenzyl)-8-hydroxyquinoline (21) 8-[a-(a’-Hydroxybenzyloxy) benzyl)-8hydroxyquinoline (22) 7-[a-(a’-Acetoxybenzyloxy) benzyl]-8-acetoxyquinoline(23) 7-[a-(a’-Hydroxybenzyloxy) benzyl]-8-methoxyquinoline (24)

Simple Reaction Products

8-Methoxyquinoline (25) N-Methyl-18methoxyquinolinium iodide (26) 8-Ethoxyquinoline (27) N-Ethyl-8-ethoxyquinolinium iodide(28) 8-Propyloxyquinoline (29) N-Propyl-8-propyloxyquinolinium bromide (30) 8-Butyloxyquinoline (31) N-Butyl-8-butyloxyquinolinium bromide(32) 8-Pentyloxyquinoline (33) N-Pentyl-8-pentyloxyquinoliniumbromide (34) 8-Benzyloxyquinoline (35) N-Benzyl-8-Benzyloxyquinolinium chloride(36) 8-Allyloxyquinoline (37) 8-(p-Nitro) benzyloxyquinoline (38) 8-Crotonoyloxyquinoline (39) 8-Acetoxyquinoline (40) 8-Benzoyloxyquinoline (41) 8-Benzenesulfonyloxyquinoline (42) 8-(p-Toluene) sulfonyloxyquinoline (43) 8-Cinnamoyloxy quinoline (44) 8-Crotonoyloxyquinolinium hydrochloride (45) 8-Cinnamoyloxyquinolinium hydrochloride (46)

Extensive spectroscopic techniques such as IR, UV, MS, GC, GCMS, 1HNMR, homodecoupling, NOE difference experiments, 13C NMR (Broad Band, DEPT), 2D-NMR (J-resolved, COSY-45, NOESY, Hetero COSY, HMQC) and chemical transformations were employed to elucidate the structures of all the isolated and synthetic compounds. The work embodies in part A and B has culminated in fifteen(15) research papers, while six (6) manuscripts are under preparation.

Download Full Thesis
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S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
502.27 KB
2 1 PART - A:-Bioassay Directed Isolation and Structure Elucidation of the Chemical Constituents of Moringa Oleifera 61
1442.99 KB
  1.1 Introduction 72
  1.2 Results and Discussion 72
  1.3 Studies on Moringa Oleifera Leaves 83
  1.4 Hypotensive Evaluation 114
  1.5 Conclusions 118
  1.6 Studies on Moringa Oleffra Pods 120
  1.7 Biological Results 149
  1.8 Conclusions 153
  1.9 Experimental 154
  1.10 References 217
3 2 PART - B:-Preparation of Biologically Significant Derivatives of 8-Hydroxyquinoline: Introduction 237
794.49 KB
  2.1 Results and Discussion 241
  2.2 Biological Results and Discussion 260
  2.3 Conclusions 277
  2.4 Experimental 278
  2.5 References 338
4 3 Appendix
94.19 KB
  3.1 List of Tables (Biosynthesis and Part A) 347
  3.2 List of Tables (Part B) 349
  3.3 List of New Substances (Part A) 351
  3.4 List of New Substances (Part B) 354
  3.5 List of Publications 355
  3.6 Vita 357