Dictionary of Alkaloids, 2nd Edition

2377 Pages·2010·33.9 MB·English

by  John Buckingham

Dictionary of
Alkaloids
SECOND EDITION
with CD-ROM

Dictionary of
Alkaloids
S E C O N D E D I T I O N
with CD-ROM
EDITED BY
John Buckingham
Keith H. Baggaley
Andrew D. Roberts
László F. Szabó
Boca Raton London New York
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Library of Congress Cataloging-in-Publication Data
Dictionary of alkaloids / editors, John Buckingham … [et al.]. -- 2nd ed. with CD-ROM
p. cm.
Includes index.
ISBN 978-1-4200-7769-8 (hardcover : alk. paper)
1. Alkaloids--Dictionaries. I. Buckingham, J. II. Title.
RS431.A53D53 2010
615’.32103--dc22 2009031445
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Table of Contents
Foreword . . . . . . . . . . . . . . . . . . . . . . . vii M. . . . . . . . . . . . . . . . . . . . . . . . . . . .1177
The Editors. . . . . . . . . . . . . . . . . . . . . . .ix N. . . . . . . . . . . . . . . . . . . . . . . . . . . .1343
Introduction . . . . . . . . . . . . . . . . . . . . . .xi O . . . . . . . . . . . . . . . . . . . . . . . . . . . .1401
Classification of Structural Types . . . . . . xxi P . . . . . . . . . . . . . . . . . . . . . . . . . . . .1445
Dictionary Entries Q . . . . . . . . . . . . . . . . . . . . . . . . . . . .1631
A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..1 R . . . . . . . . . . . . . . . . . . . . . . . . . . . .1647
B . . . . . . . . . . . . . . . . . . . . . . . . . . . . .261 S . . . . . . . . . . . . . . . . . . . . . . . . . . . .1687
C . . . . . . . . . . . . . . . . . . . . . . . . . . . . .341 T . . . . . . . . . . . . . . . . . . . . . . . . . . . .1815
D. . . . . . . . . . . . . . . . . . . . . . . . . . . . .523 U. . . . . . . . . . . . . . . . . . . . . . . . . . . .1965
E . . . . . . . . . . . . . . . . . . . . . . . . . . . . .699 V . . . . . . . . . . . . . . . . . . . . . . . . . . . .1977
F . . . . . . . . . . . . . . . . . . . . . . . . . . . . .761 W. . . . . . . . . . . . . . . . . . . . . . . . . . . .2015
G. . . . . . . . . . . . . . . . . . . . . . . . . . . . .805 X . . . . . . . . . . . . . . . . . . . . . . . . . . . .2021
H. . . . . . . . . . . . . . . . . . . . . . . . . . . . .849 Y . . . . . . . . . . . . . . . . . . . . . . . . . . . .2029
I. . . . . . . . . . . . . . . . . . . . . . . . . . . . .1007 Z . . . . . . . . . . . . . . . . . . . . . . . . . . . .2035
J. . . . . . . . . . . . . . . . . . . . . . . . . . . . 1073 Name Index . . . . . . . . . . . . . . . . . . . .2043
K. . . . . . . . . . . . . . . . . . . . . . . . . . . .1085 Compound Index Contents. . . . . . . . . .2243
L . . . . . . . . . . . . . . . . . . . . . . . . . . . .1107 Type of Compound Index. . . . . . . . . . .2245
v

Foreword
Plants containing alkaloids have served humankind since ancient times. Indeed, some of the oldest surviving
written records of commercial transactions involving medicinal plants are of alkaloid-containing plants. For
thousands of years, indigenous groups around the world discovered, through self-experimentation with locally
availableplantextracts,thattheycouldprovidematerialsforhuntingprey,culinaryenhancement,amelioration
from disease, relief of pain, and healing. These plants contributed significantly to the survival of indigenous
groups throughout history. This same process of low-throughput clinical screening also identified many plants
which were to be avoided because of their toxicity, again due to alkaloids. It is the oral and written records of
theseinvestigationswhichsurvivetodayandformthebasisofbothclinicalcareinmuchoftheworldandaspects
of contemporary drug discovery.
A transition occurred at the beginning of the 19th century when investigations on the most significant
medicinal and toxic plants of Europe commenced, these included studies on opium, colchicum, nux vomica,
ipecac,belladonna,andpepper.Asittranspired,alloftheisolated,biologicallyactivecompoundswerealkaloids,
anditwastheseinvestigationswhichinitiatedthediversestudiesofalkaloidsasaclassofnaturalproductswhich
continue today.
Since those early times, there have been six important phases to the study of alkaloids. The first was the
tremendousincreaseinthenumberofstructurallyuniqueandcomplexalkaloidsisolatedfromplants,structures
which defined the new field of heterocyclic chemistry. The second was the dramatic reduction in time and the
amount of material required to determine the precise stereochemical and conformational structure of an
individualalkaloidasaresultoftheadvancesinspectroscopicandchromatographictechniqueswhichpermitted
ever smaller samples to be structurally characterized. Third, there evolved the understanding that groups of
structurally similar alkaloids could, sometimes, be related to each other based on one or two biosynthetic
precursorsfromwhichchemicallyrationalmetabolicschemescouldbeusedtogeneratetheplethoraofalkaloid
skeleta and structures. Fourth, there was the recognition that this structural diversity, skeletal complexity, and
stereo-uniquenesswereatthesametimeabenefitandabane.Whiletheactivitycouldbeexquisite,alkaloidsmay
also have significantly modulated biological activity based on a transformation at a single functional group or
stereochemical center. Fifth, as more complex alkaloids were structurally elucidated they became challenging
targets for synthetic organic chemists, and continue to be the basis for the stimulation of numerous brilliant
synthetic strategies and innovations in organic chemistry. Finally, as knowledge of the biology associated with
alkaloidsgrewinbothbreadthanddepth,initiallyattheinvivolevelandeventuallyatthemolecularlevel,some
alkaloids were established to be archetypal entity for a particular biological response.
Consequently, in this 200-year period, many alkaloids became critical components of the global
pharmaceutical armamentarium, and tremendous healing has resulted from their clinical application. As our
foodandbeveragepracticeshaveevolved, alkaloids havebecome acorecomponentofeverydaylifeforalmost
everyoneontheplanetonamomenttomomentbasis,andcaffeine,capsaicin,nicotine,theobromine,adrenaline,
dopamine, serotonin, etc. are representative examples. Many of the colors of flowers and vegetables are due to
alkaloids, and at the same time, alkaloids represent enormous and potent biological power. Sometimes this
powercanbeamelioratedbydosereductiontoproducehealthbeneficentagents(forexample,theergotalkaloids
and aconitine); in other instances they must simply be avoided by both animals and humans, such as those in
manytoxicplants,animals,andfungi.Alkaloidsalsohaveledmedicinalchemistsdownproductivepathwaysfor
drug development, although it is seldom appreciated that the molecular phylogeny of many synthetic drugs can
be traced to classical alkaloids such as morphine and atropine. At the same time, there is a ‘‘dark side’’ to
alkaloids, because at least three - morphine, cocaine, and nicotine - have powerful social implications causing
tremendoushumansufferingthroughaddiction,diseasedevelopment,andwarswhichcontinueunabatedtoday.
It is this good, bad, and downright ugly aspect to alkaloids which has fascinated so many scientists forso long.
Asaglobalsocietywedoindeedhavethislove-haterelationshipwithalkaloidsunlikethatofanyothergroupof
natural products.
Asmentioned,withtheriseofspectroscopybeginninginthe1950s,interestdevelopedinexaminingalkaloids
from wider sources than higher plants. Indeed, it appears now that almost every class of organism, insects,
reptiles, birds, fungi, bacteria, the diversity of marine organisms, and mammals, including humans, all produce
alkaloids. The last twenty years have witnessed an explosion in the numbers and the structural diversity of
alkaloids from these sources, and these developments are dramatically reflected in this updated compilation.
vii
From a chemical perspective, it transpires that there is almost no overlap in the structural diversity of plant,
fungal,andmarinealkaloids.Eachisachemicallybrilliantworlduntoitself.Thus,onewouldnotexpecttofind
a monoterpenoid indole alkaloid in a marine sponge, nor a manzamine alkaloid in a tropical liana. This
unimaginable structural diversity places the alkaloid sciences on the cusp of a deeper understanding of their
biosynthetic formation. While significant and successful efforts are underway to elucidate pathways and isolate
genes which are related to both plant and fungal alkaloids, for marine organisms this aspect is completely
unexplored, although the most spectacular new skeleta and potent biological activities are derived from these
marine sources.
Thepasttwentyyearshavewitnessedtheevolutionofthreenewareasofalkaloidchemistryandbiology.The
firstisthatoftheintegrityofalkaloidbiosynthesis.AlkaloidssuchtheansamacrolidesfromMaytenusandfrom
Colubrina,aswellastheergotalkaloidsoftheConvolvulaceaearenowestablishedtobederivedbiosynthetically
from parasitic or symbiotic fungal organisms, not through the metabolic pathways of the host plant. Second,
structuralconclusionsregardingindividualalkaloidscanchange;ana-hydroxygroupofyesterdaycanbecomea
b-hydroxy today based on refined chemical, spectroscopic, and crystallographic conclusions. As one looks
throughtheDictionaryofAlkaloids,itisimportanttobeawarethattherearemanyexampleswherethesynthesis
ofaproposedstructurehasfailedtosupportthatstructure,orwherenewspectroscopicevidencedoesnotsupport
aproposedstructure.Whileinsomecasesthishasledtorefinementofthestructure,inothersadanglingquestion
remains as to the true identity of the natural alkaloid. Third, there is the connection of alkaloids to the
biotechnology revolution, and the marvelous progress that has been made for certain alkaloid pathways in
elucidating the enzymes and genes of alkaloid biosynthesis.
What, then, is the ‘‘fit’’ for the Dictionary of Alkaloids, and why is it such an important resource for
researchers?Burgeoningeffortsatstructureelucidationandbiologicalexperimentationmakeitextremelydifficult
to quickly find key literature citations to original sources of information on individual compounds. It was
recognized some years ago that there was a core global need for information systems on the isolation, spectral
properties, and biological properties of alkaloids. The Dictionary of Alkaloids is a critical, absolutely essential
componentinfillingthatneed.Itistheonlyaccumulation intheworldofthetaxonomy,chemistry,andbiology
of alkaloids derived from all sources. It provides extensive information to references for the isolation,
spectroscopy, and biology of an individual alkaloid, and to its other attributes and uses. Importantly, the
alkaloids are frequently collected as a group based on a parent structure. This simplifies the presentation, and
accumulatesalkaloidshavingquitedifferenttrivialnames.Thevolumeiseasytouse,andthediverseindexesplace
themostsignificantinformationatone’sfingertips.Itisauniqueresource,andonewhichisindispensabletoany
alkaloid chemist and biologist. The inclusion of a fully substructure searchable CD-ROM in this second edition
makes the resource even more valuable.
In spite of the vast range of studies of alkaloids over the years, much remains to be done. There are many
plantfamilieswhichareknowntocontainalkaloidswherethealkaloidsremaintobeidentified;thereareuntold
marine organisms and tens of thousands of microorganisms with unknown alkaloids. There is the genetics of
alkaloid biosynthesis in more diverse organisms, and the tremendous potential for being able to produce
alkaloids through isolated and stabilized systems in a sustainable manner. The key justification for alkaloid
research, though, must be relevance to the enhancement of public health. For many years, justification for
alkaloidresearch wasbased ontheir novelty;there was norelationship tobiology.Indeed, it was shown several
years ago that about 75% of all plant alkaloids had never been evaluated in a single bioassay. There remains a
critical need for the wider biological study of known and new alkaloids in high throughput screening systems.
Alkaloids will continue to have a critical role to play in the health of the Earth and of its inhabitants for the
foreseeablefuture.Theyrepresentasignificantaspectintheevolvingconceptofsustainabledrugsandbiological
agents.However,onlythroughtheextensivecollaborationoftaxonomists,chemists,biologists,pharmacologists,
formulation chemists, and clinicians can this potential be realized.
Inthe12thcentury,accordingtoMatthewFoxin‘‘OriginalBlessing,’’itwasSaintHildegardofBingenwho,
indiscussingtherelationshipofhumankindandNatureinphilosophicalandpracticalterms,suggestedthat‘‘All
nature is at the disposal of humankind. We are to work with it. For without it, we cannot survive.’’ Rather like
humankind, alkaloids, in all of their stunningly beautiful complexity and diversity, are an integral and essential
aspect of nature with which we must work to survive.
Geoffrey A. Cordell, Ph.D.
Professor Emeritus
Evanston, IL USA
viii
The Editors
John Buckingham is a former lecturer in organic chemistry at the University of London. He has been involved
with the Chapman & Hall (now CRC) chemical database since its inception in 1980, initially as a Chapman &
Hall employee, more recently as Editorial consultant. From the database has been producedvarious editions of
theDictionaryofOrganic CompoundsandtheDictionaryofNaturalProducts(bothofwhichhavebeenforsome
years solely electronic). In addition, he compiled (with I.W. Southon) the first edition of the Dictionary of
Alkaloids(printonly)in1989.HeisalsotheauthorofthepopularsciencebooksChasingtheMoleculeandBitter
Nemesis; The Intimate History of Strychnine
KeithH.BaggaleyobtainedhisBSc(Hons)andPhDdegreesfromtheUniversityCollegeofWales,Aberystwyth
followed by a post-doctoral fellowship in chemistry at the Royal Institute of Technology, Stockholm, Sweden,
with Professor Holger Erdtman and Professor Torbjorn Norin. He then took up a Junior Research Fellowship
withProfessorDavidOllisattheUniversityofSheffieldbeforejoiningBeechamResearchLaboratoriesinSurrey
as a research chemist. At Beecham he worked on discovery projects concerned with cholesterol lowering drugs,
platelet aggregation inhibitors and semisynthetic antibiotics as well as research on clavulanic acid biosynthesis.
He has been an editor of the Chapman & Hall dictionaries since 1996.
Andrew D. Roberts took his BSc (Hons) degree at Trent Polytechnic, Nottingham (now Nottingham Trent
University), UK 1973(cid:1)1977 and completed studies in drug discovery projects at Pfizer (Sandwich) UK. He
contributed to the Dictionary of Organic Compounds (Chapman & Hall) published in 1982 and has since been
a Contributing Editor for other projects including the Dictionary of Antibiotic Substances (1988), Dictionary
of Drugs (1990) and has since been an Editor on the Dictionary of Natural Products which was first published
in 1993.
La´szloo´ Ferenc Szabo´ was born in Szentgottha´rd (Hungary) on April 15, 1931 and studied in Pharmacy at
University of Medicine, Budapest, 1949(cid:1)54. Member of the Department of Medicinal Chemistry, later of the
Department of Organic Chemistry of the Semmelweis University Budapest (scientific assistant, associate
professor, ordinary professor), director of the same department 1977(cid:1)1996, Ph.D. in organic chemistry, Doctor
habilitatus. Research visitor at Universite´ Libre de Bruxelles, 1972/73, several times in Merseburg (Germany).
Presently professor emeritus of the Semmelweis University. Fields of activity: chemistry of natural products,
mainlyindolealkaloids(strychnine,strictosidine)andterpenoids(iridoids,secologanin),biogeneticformationof
natural products, heterocyclic chemistry, mainly quinolizine compounds, polymer supported synthesis of small
molecules, theoretical problems of organic chemistry (PMO theory, graph analysis).
IN HOUSE EDITORIAL TEAM
Prof. R.A. Hill, University of Glasgow
Dr A.M. Hodgson, Consultant
Dr F.M. Macdonald, CRC Press, Boca Raton
Dr S.P. Walford, CRC Press, London
Additional data collected by contributors to the CRC Chemical Database
ix