Bioactive alkaloids from medicinal plants of Lombok

298 Pages·2013·6.78 MB·English

University of Wollongong
Research Online
University of Wollongong Thesis Collection University of Wollongong Thesis Collections
2002
Bioactive alkaloids from medicinal plants of
Lombok
Surya Hadi
University of Wollongong
Recommended Citation
Hadi, Surya, Bioactive alkaloids from medicinal plants of Lombok, Doctor of Philosophy thesis, Department of Chemistry, University
of Wollongong, 2002. http://ro.uow.edu.au/theses/1117
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BIOACTIVE ALKALOIDS FROM MEDICINAL
PLANTS OF LOMBOK
A Thesis Submitted in Fulfillment ofthe Requirements
for the Award ofthe Degree
of
DOCTOR OF PHILOSOPHY
from
The University of Wollongong
by
SURYA HADI, Ir. M.Sc. (Hons.)
Department of Chemistry
October 2002
CERTIFICATION
I, Surya Hadi, declare that this thesis, submitted in fulfillment
of requirement for the award of Doctor of Philosophy, in the
Department of Chemistry, University of Wollongong, is
wholly my own work unless otherwise referenced or
acknowledge. The document has not been submitted for
qualifications at any other academic institution.
SURYA HADI
10 October 2002
u
PUBLICATIONS
1. Initial Studies on Alkaloids from Lombok Medicinal Plants (Molecules)1
2. Constituents of Medicinal Plants of Lombok: A New Antibacterial Alkaloid from
Voacangafoetida (Bl.) Rolfe (Phytochernistry, in preparation)
3. New Bioactive Alkaloids from Young Trees of Alstonia scholaris R. Br. (Planta
Medica, in preparation)
(1) Hadi, S.; Bremner, J. B. Initial studies on alkaloids from Lombok medicinal plants. Molecules
[online computer file] 2001, 6, 117-129.
Ill
ACKNOWLEDGEMENTS
I would like to give my sincere thanks to my supervisor, Prof. John B. Bremner for his
continuous guidance and support during the course of this study. Thanks are extended to
Aus Aid for the scholarship and to the Institute for Biomolecular Science in providing extra
funds to assist this project.
My utmost thanks to the following people Who extended their kind aid in completing this
work: Dr. John Korth for training me to operate the Low Resolution Chemical
Ionisation/Electron Impact Mass Spectrometer; Larry Hick for his help in performing High
Resolution Chemical Ionisation/Electron Impact Mass Spectrometry; the NMR people,
Sandra Chapman, Ellen Manning, and Yoke Berry for their assistance in training me in
using the NMR spectrometer; Dr. David Perkins, not only for his kind help in correcting
my thesis but also for his warm friendship; Dr. Irawati and Mr. Made Sudana for their
great contribution to facilitate the collection of medicinal plants; Mr. Taspin for his help in
collecting the plants; Dr. Kirsten Benkendorff for her guidance in the antibacterial testing;
Dr. Sumalee Kamchonwongpaisan for the antimalarial testing; and finally to my best
friends in the Bremner research group, Susan, Collette, Waya, Siritron, Nisit, Johana, and
Burak (Dr. Coban) for their uncountable help and friendship.
iv
TABLE OF CONTENTS
Certification ii
Publications iii
Acknowledgements iv
Table of Contents v
List of Abbreviations ix
Abstract xi
Chapter 1
INTRODUCTION 1
1.1. General 1
1.2. Resistance to Antibacterial Agents 3
1.3. Resistance to Antimalarial Agents 5
1.4. The Importance of Alkaloids in Drug Discovery 6
1.4.1. Alkaloids in Plants 7
1.4.2. Contribution of Alkaloids to Humankind 8
1.4.3. Alkaloids and Drug Discovery 9
1.5. Lombok and Natural Products Development 11
1.6. The Aims ofthe Study 12
Chapter 2
SELECTION OF PLANT MATERIALS 14
2.1. General 14
2.2. Approaches to Plant Selection 15
2.3. Medicinal Plant Use in Lombok 16
v
2.4. Alkaloid Screening 17
2.5. Collection of Lombok Medicinal Plants 18
2.6. Previous Work and Geographical Distribution of Alkaloid Positive Species 25
2.7. Plants Selected for Further Study 36
Chapter 3
ALKALOIDS F R OM Voacangafoetida (Bl.) Rolfe 38
3.1. Introduction 38
3.2. Indole Alkaloids: Biosynthesis and Classification 39
3.3. Alkaloids from the Genus Voacanga 47
3.4. Isolation and Structural Elucidation of Alkaloids from Voacangafoetida (Bl.) Rolfe
50
3.4.1. Lombine 50
3.4.2. Voacangine 57
3.4.3. Coronaridine 58
3.4.3. Voacristine 61
Chapter 4
ALKALOIDS F R OM Psychotria malayana Jack 66
4.1. Introduction 66
4.2. Alkaloids from the Genus Psychotria 67
4.3. Biosynthesis of Calycanthine Type Alkaloids 76
4.4. Isolation and Structure Elucidation of Alkaloids from Psychotria malayana Jack.78
4.4.1. Hodgkinsine 79
4.4.2. MesoChimonanthine and /.yo-Calycanthine 81
4.4.3. The Alkaloid LPM-574 83
4.4.4. The Alkaloid LPM-186 85
vi
Chapter 5
ALKALOIDS FROM Alstonia scholaris R. Br 87
5.1. Introduction 87
5.2. Alkaloids from the Genus Alstonia 88
5.3. Antiplasmodial Activity of Alstonia Alkaloids 95
5.4. Isolation and Structure Elucidation of Alkaloids from A. scholaris R. Br 101
5.4.1. Mataranine A and B 101
5.4.2. Alstonamine (Angustilobine B) 106
5.4.3. (15S* io^-Losbanine 109
5.4.4. Kotarajine 113
5.4.5. (£AAkuammidine 115
Chapter 6
ALKALOIDS FROM Clerodendron calamitosum L. and Clerodendron paniculatum L.118
6.1. Introduction 118
6.2. Alkaloids from the Family Verbenaceae 119
6.3. Isolation and Structure Elucidation of Alkaloids from C. calamitosum L. and C.
paniculatum L 124
6.3.1. Alkaloids from C. calamitosum L 124
4.3.2. Alkaloids from C. paniculatum L 130
Chapter 7
ANTIMICROBIAL TESTING 133
7.1. Introduction 133
7.2. Assays for Detecting Antibacterial Activity 134
7.3. Assays for Detecting Antimalarial Activity 137
7.4. Results of Antibacterial Testing 140
7.4.1. Voacangafoetida (Bl.) Rolfe 140
7.4.2. Psychotria malayana Jack 143
7.4.3. Clerodendron calamitosum L. and Clerodendron paniculatum L 144
7.5. Results of Antimalarial Testing 145
vu
Chapter 8
CONCLUSIONS AND FUTURE WORK 147
8.1. Conclusions 147
8.2. Future Work 152
Chapter 9
EXPERIMENTAL SECTION 153
9.1. General 153
9.2. Plant Collection 154
9.3. Alkaloid Screening 155
9.4. Alkaloid Isolation Procedure 156
9.4.1. Isolation and Purification of Alkaloids from Voacangafoetida (Bl.) Rolf. 159
9.4.2. Isolation and Purification of Alkaloids from Psychotria malayana Jack.... 164
9.4.3. Isolation and Purification of Alkaloids from Alstonia scholaris R. Br 168
9.4.4. Isolation and Purification of Alkaloids from Clerodendron calamitosum L. and
C. paniculatum L 173
9.5. Antibacterial Assay 178
9.5.1. Sample Preparation 178
9.5.2. Antibacterial Test Procedure 178
9.6. Antimalarial Assay 179
9.6.1. Sample Preparation 179
9.6.2. Procedure of Antimalarial Activity Testing 179
REFERENCES 181
APPENDICES 209
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