PLANT ALKALOIDS - Sciencemadness.org

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THE
PLANT ALKALOIDS
BY
THOMAS ANDERSON HENRY
D.Sc.(Lond.),
Formerly Director, Wellcome Chemical Research
Laboratories and Superintendent of Laboratories,
Imperial Institute, I Minion.
FOURTH EDITION
THE BLAKISTON COMPANY
Philadelphia • Toronto
1949
First edition . • 1913
Second edition • 1924
Third edition . • 1939
Fourth edition • 1949
This book is copyright. It may not be
reproduced by any means, in whole or in
part, without permission. Application
with regard to copyright should be
addressed to the Publishers.
Printed in Great Britain
and published in London by
J. &• A. Churchill Ltd.
104 Gloucester Place, W.i,
PREFACE TO THE FOURTH EDITION
So much information concerning alkaloids has been published since
the third edition of this book was issued in 1939, that the preparation of
a new edition has involved re-writing a large part of the volume and
adding considerably to its bulk.
The material available has been dealt with, as in the previous edition,
primarily on the basis of a chemical classification according to nuclear
structure, but as Nature does not produce alkaloids to meet the needs of
either botanical or chemical systematists, strict observance of such a
system would in some measure obscure those biological relationships
among alkaloids which are at present attracting much attention from
research workers. Accordingly this primary chemical classification has
been modified, in cases where an extensive series, including several
chemical types, occurs in one plant, or in closely related plants. When
this results in a chemical group being dealt with in more than one place,
cross references have been provided as a convenience to the reader.
The author is. much indebted to Mr. L. G. Goodwin, B.Sc, B.Pharm.,
for reading certain of the pharmacological sections, and to Dr. S. Smith
and Dr. A. C. White for advice on various points on which they are
recognised experts. He also owes grateful thanks to Mrs. Henry for
unstinted help in checking references, reading proofs and the maintenance
of an index to the literature of alkaloids. The preparation of the type
script, and the typing of the numerous new and complicated graphic
formulae, in a form suitable for photographic reproduction, was undertaken
by Miss I. Bellis, to whom the author is greatly indebted for the untiring
patience and meticulous care she has devoted to this task. He has also
to thank the publishers for the kindly and sympathetic consideration they
have given to all the technical problems raised in the course of printing
the volume. Finally, the author owes to the customary generosity of the
Wellcome Foundation Limited office accommodation and working
facilities, without which this book could not have been prepared.
T. A. HENRY.
LONDON.
PREFACE TO THE FIRST EDITION
IN certain respects the plant alkaloids rank among the most interesting
of naturally occurring substances. For the most part they are of complex
structure, so that the determination of their constitution and the discovery
of methods of producing them synthetically offer attractive problems to
the chemist; and though a great deal has been accomplished, much still
remains to be done in this direction. Their mode of origin and their
function in plants are still unknown, and these two questions, with the
more important one of correlating the structure of the alkaloids with
their physiological action, form still almost untouched fields for combined
work on the part of physiologists and chemists. Many of the alkaloids
are of great importance in medicine, and the manufacture of these alkaloids
and of products containing them constitutes an important branch of the
" fine chemical " industry.
In compiling this volume the author has kept in view these various
as_pects of the subject, and the articles on all the more important alkaloids
describe not only the properties and the chemistry of these products, but
also their occurrence, methods of estimation, and physiological action.
In most cases the original memoirs have been consulted, and references
to these are given in footnotes, but for descriptions of the physiological
action of the better-known alkaloids Professor Cushny's " Textbook of
Pharmacology and Therapeutics " has been largely utilised. The chemical
nomenclature and the system of abbreviations used are, with a few
unimportant exceptions, those employed in the " Abstracts " published
by the Chemical Society of London, with which most English-speaking
chemists are familiar.
For much laborious work in checking formula? and references and in
reading proofs, the author is indebted to Mrs. Henry, B.A., B.Sc. (Lond.),
and to Miss A. Holmes, B.A. (Lond.).
vl
CONTENTS
PAGE
Introduction 1X
Pyridine Group. Piperine, Piperovatine, Leueenol, Mimosine,
Alkaloids of Ricinus communis, Fcenugrec, Areca Nut, Hemlock,
Lobelia, Tobacco (Nicotiana spp.), Anabasis aphylla, Pome
granate Root Bark . . . . . . .. 1
Tropane Group. Solanacedus Alkaloids, Convolvine and Allied
Alkaloids, Dioscorine, Alkaloids of Coca Leaves (Erythroxylon
coca) 64
Lupinane Group. Alkaloids of the Papilionacese: Lupinine,
Lupanine, Sparteine, Anagyrine, Cytisine, Matrine and Asso
ciated Bases . . . . . . . • . 116
isoQuinoline Group. Alkaloids of
Cactaceas : Mezcaline, etc. . . . . . .. 154
Hydrastis canadensis: Hydrastine . . . . .162
Rhceadales . . . . . . . .. 169
Opium (Papaver somniferum) : BenzyKsoquinolines ; Phthalide-
isoquinolines ; Morphine Sub-group, Sinomenium acutum . 175
Other Papaver spp. : Rhceadine, etc. . . . .. 274
Other Papaveraceous Genera : a-Naphthaphenanthridines . 277
Corydalis and Allied Genera: Tetrahydrc>proioberberines;
Cryptopine Sub-Group ; Aporphine Sub-group . . . 284
Anonaceae, Lauraceae, Monimiacese; Anolobine, etc. . . 317
Berberis and Related Bases ; Berberine, Canadine, Palmatine,
Coptisine, etc. . . . . . . . .. 328
BISBENZYLwoQUINOLINE SUB-GROUP
Berbamine, Oxyacanthine . . . . . . . 346
Alkaloids of the Menispermacese; Coclaurine, Dauricine,
Magnoline, Tetrandrine, Bebeerine, etc 349
Alkaloids of Curare ; Curine, Tubocurarine, Protocuridine,
Calabash-curare I, etc., including Erythrina alkaloids . 371
Alkaloids of Ipecacuanha . . . . . . 394
Phenanthridine Group. Alkaloids of the Amaryllidacese ; Lycorine,
etc 406
vii
viii CONTENTS
PAGE
Quinoline Group. Dictamnine, Skimmianine, Fagarine 413
Alkaloids of
Cusparia Bark . . .. 415
Cinchona spp. . . .. 418
Indole Group. Abrine, Gramine, Calycanthine 484
Alkaloids of
Peganum harmala 488
Evodia rutcecarpa . 498
Yohimbe, Quebracho, etc. 500
Ergot . 517
Calabar Bean 539
Strychnosr spp. 553
Pyrrolidine Group 599
Pyrrolidine Group 601
Quinazoline Group 617
Glyoxaline Group 621
Alkaloidal Amines 630
Steroidal Alkaloid Group 661
Alkaloids of Undetermined Constitution 716
Minor Alkaloids 771
Recorded Occurrences of Alkaloids 779
Index 784
PLANT ALKALOIDS
INTRODUCTION
THE literature of alkaloids can conveniently be divided into five
sections, dealing with (1) the occurrence and distribution of these substances
in plants ; (2) biogenesis, or the methods by which alkaloids are produced
in the course of plant metabolism; (3) analysis, ranging from the commer
cial and industrial estimation of particular alkaloids to the separation,
purification and description of the individual components of the natural
mixture of alkaloids, which normally occurs in plants ; (4) determination
of structure ; and (5) pharmacological action.
In the period that has elapsed since the third edition of this book was
published there have been additions to each of these sections, and to
some of them the new contributions have been numerous and important.
Many new alkaloids have been described and new occurrences recorded.
An interesting feature of this section of work is the operation of a number
of what may be called alkaloidal surveys, ranging from searches for
alkaloidal plants to investigations of plants of a particular botanical
order, or of a selected botanical genus, or of geographical or other variants
of a single species. In Soviet Russia, Massagetov 1 has made a preliminary
examination of 113 species collected in Central Asia, out of which he has
found promising materials among lichens, mosses and liverworts, some
varieties of maize, cotton and beans, certain species of Picea and Pinus,
and a specially rich source in Dipsacus azureus belonging to the Dipsacaceae,
a botanical family which like the allied Composite, has not been a frequent
source of alkaloids. In the same country, in 1939, Lazur'evskii and
Sadikov 2 examined over 200 plants collected by various expeditions in
Central Asia and recorded alkaloids in a number of species, including
Aconitum talassicum and Convolvulus hamadce, the alkaloids of which have
since then been investigated in detail as described later. Mention may
also be made of the comprehensive volume on " The Poison Plants of New
South Wales," compiled by Evelyn Hurst under the direction of the
Poison Plants Committee of the University of Sydney. It includes numerous
monographs on plants containing toxic alkaloids and should be of great
value to research workers concerned with plant chemistry.
In the course of the intensive campaign carried on in the United
States of America during the war for the discovery of effective anti
malarial drugs, a team of workers 3 made anti-malarial tests on 600 different
plants belonging to 123 families of phanerogams and three families of
cryptogams, and it is recorded that the suppressive activity shown by
some of these plants appeared to be associated with alkaloidal fractions
of their extracts.
ix
X INTRODUCTION
Of surveys with a narrower alkaloidal objective, mention may be
made of the systematic work done by E. P. White and his collaborators
in ascertaining the distribution of perloline in Lolium and allied grasses in
New Zealand, and that of the same author in the examination of over
200 leguminous species, to ascertain the nature of their alkaloidal compo
nents and the effect of conditions on the alkaloidal content of various
organs. Manske's work on alkaloids of Fumaraceous plants and of
Lycopodium species also needs mention in this connection; it has not
only resulted in new and interesting additions to the list of alkaloids, but
the results, like those of White, have a bearing on the suggestion sometimes
made that the nature of the substances present in plants may usefully
be taken into account in some taxonomical problems. This suggestion is
not as novel as is sometimes supposed, and Raymond-Hamet,4 in his
paper maintaining the separation of Chevalier's genus Pseudocinchona
from Corynanthe, on the ground that Pseudocinchona africana contains
the alkaloids corynanthine and corynantheine, whereas Corynanthe
paniculata yields yohimbine, makes the following statement: " Alphonse
de Candolle a affirme que les phenomenes de physiologie (et par consequent
les propriety biochimiques et notamment la composition chimique)
peuvent etre envisages . . . comme caracteres d'une espece, d'un genre,
d'une famille, d'une classe de vegetaux." 5
In this connection Manske 6 has suggested that the question whether
Fumariacese and Papaveraceae, together forming the order Rhceadales,
should continue to be regarded as separate botanical families or be merged,
can be settled in favour of the second alternative by a consideration of
the nature of the alkaloids present in the plants, and he provides in support
an interesting summary of existing information on this point. On the
other hand, the number of cases of the occurrence of the same alkaloid in
plants, which cannot be regarded as closely related botanically, justifies
taxonomists in being cautious about freely accepting chemical evidence
of this kind. Nicotine, for example, is found not only in the Solanaceous
genera Nicotiana and Duboisia, but also in Asclepias (Asclepiadaceae),
Equisetum (Equisetacese), Lycopodium (Lycopodiacese), Sedum acre
(Crassulacese) and Eclipta alba (Compositse), and as further instances,
anabasine occurs both in Nicotiana glauca and Anabasis aphylla (Cheno-
podiaceae), whilst ephedrine is not only present in Ephedra spp. (Ephe-
draceffi), but has also been recorded from Taxus baccata (Taxaceae) and
Sida rhombifolia (Malvaceae) and its near relative <J-nor-</i-ephedrine is the
" cathine " of Catha edulis (Celastracese). More remarkable still is the
case of berberine, which occurs in at least sixteen genera belonging to six
different botanical families. Further, alkaloids of quite different types
may occur in the same plant, for example in the opium poppy, and in
Aconitum Napellus, in which ephedrine and sparteine have been recorded,
as well as the typical aconite alkaloids. More information is in fact needed
of the kind provided by the surveys undertaken by White and by Manske
before chemical knowledge of plant constituents can be safely and generally
applied to problems of plant classification. In the introduction to his
INTRODUCTION XI
series of papers on the alkaloids of the Leguminosae, White points out that
although this order has been investigated perhaps more than any other
for alkaloids, there is still uncertainty regarding the nature and distribution
of alkaloids even in some common species, that little is known of the alka
loid content of common European plants grown under new conditions, for
example in the Southern Hemisphere, that a large number of factors are
capable of altering the alkaloidal content in quantity and nature, and that
in much of the older European literature there is uncertainty due to
incomplete chemical investigation.
Although the number of alkaloids still in use in medicine is small,
serious difficulty was caused by the war, due to the cutting-off of the
usual sources of supply of the natural drugs which yield essential alkaloids,
such as atropine, cocaine, hyoscine, morphine, emetine and ergometrine.
Shortages were met as far as possible by new sources of supply and by
local cultivation of the opium poppy, belladonna and other necessary
drugs. This necessity provided new opportunities for the collection of
experimental data regarding the possibility of plant selection and ot the
effects of environment and of changes in cultural conditions on yield of
alkaloids. An interesting account of the kind of work this involves will
be found in the paper by W. O. James referred to below. One outcome
of this work is the observation by workers in several countries that in
solanaceous plants the tropane alkaloids are formed mainly in the roots.7
The plants generally used were belladonna, stramonium and Duboisia spp.,
and the necessary cultivation experiments were similar to those briefly
described under the alkaloids of tobacco. The problem is, however, more
complex than the results of these special observations seem to imply,
and W. O. James,8 in the course of an account of work done by the Oxford
Medicinal Plants Scheme on the biosynthesis of the belladonna alkaloids,
states that alkaloids are first formed in the meristem of the radicle and
can be detected when the radicles are 3 mm. long, but also shows that
detached belladonna leaves can be induced to increase their alkaloidal
content. He concludes that on the evidence available it is possible that the
leaf alkaloids have a dual origin : by synthesis in situ and by translocation
from the root.
A curious observation, first made by Barnard and Finnemore 9 in the
course of a systematic examination of Duboisia myoporoides in the whole
range of its distribution in Australia, is that in this plant the relative
proportions of the two main alkaloids is extremely variable, hyoscine being
predominant in plants of the northern area and hyoscyamine in those of
the southern region. Hills, Trautner and Rod well,9 continuing this work,
confirmed this general result, but in the course of selection trials found
that individual trees could exhibit the same variation ; the leaves of one
specimen at Nambour, Queensland, contained in October about 3 per
cent, of almost pure hyoscyamine and in April about the same amount of
almost pure hyoscine. Trautner,10 in a paper dealing with these anomalies,
and also discussing the possible modes of origin of the various amino-
alcohols, tropine, 0-tropine, scopine, etc., and of the acids, tropic, benzoic,
xii INTRODUCTION
veratric, tiglic and isovaleric, which esterify them, suggests that in
Duboisia and other solanaceous species two systems are in operation.
The hyoscine system occurs alone in certain northern Duboisia myo-
poroides, and forms scopine, ^r-tropine, dihydroxytropane and, in Datura
meteloides, teloidine. Of these amino-alcohols, all the scopine is esterified
by tropic acid and the minor bases by tiglic, methylbutyric or isovaleric
acid, which contain the isoprene skeleton and are presumed to arise from
that source.
The hyoscyamine system is found alone in some adult Duboisia
Leichhardtii and possibly in some southern D. myoporoides. It produces
tropine and nortropine only, which are esterified with tropic acid, or as in
apoatropine found in belladonna, with atropic acid, and to a small extent
with the isoprene acids referred to above. Some tropine or nortropine
may occur as such. Scopine, ^-tropine and dihydroxytropane are atfeent.
The hyoscine system occurs alone in all young plants and may
continue throughout life in specimens in the northern area : it may
represent the original alkaloid metabolism of the plant. The hyoscyamine
system appears only at the age of four to six months, and in the southern
area it replaces the hyoscine system almost completely ; it appears to be
an adapted system and may represent the adult alkaloid metabolism of
the plant. Usually both systems are present in varying proportions.
It may be noted that Datura Metel, in which hyoscine is usually the
predominant alkaloid, has been recorded in one instance by Libizov u as
containing hyoscyamine, but no hyoscine, and a similar difference is
mentioned for Scopolia lurida.11
In Robinson's now well-known suggestions,12 regarding the processes
by which alkaloids may be produced in plants, two main reactions are
used ; the aldol condensation and the similar condensation of carbinol-
amines, resulting from the combination of an aldehyde or ketone with
ammonia or an amine, and containing the group . C(OH) . N., with
substances in which the group . CH . CO . is present. By these reactions
it is possible to form the alkaloid skeleton, and the further necessary
changes postulated include oxidations or reductions and elimination of
water for the formation of an aromatic nucleus or of an ethylene derivative.
This theory has stimulated activity in two main directions, suggestions
for changes in detail in the steps of processes for particular alkaloids, and
work on laboratory syntheses of known alkaloids, using the reactions
specified and operated under conditions which might obtain in a plant,
i.e., under what are now described as physiological conditions. All the
results indicate that the theory is well-founded, and it seems possible that
a technique may eventually be found by which the process may be observed
in operation, directly or indirectly, in situ, say in a solanaceous plant.
After determination of the seasonal variation in alkaloidal content of
the leaves, stems and roots of belladonna and the production of evidence
that there is a considerable movement of alkaloid upwards from root to
leaves and a small transport in the opposite direction, Cromwell13 found
that of a large number of amines injected, with or without glucose, into