raffauf - plant alkaloids - a guide to their discovery and distribution [dp] (fpf, 1996)

FOOD PRODUCTS PRESS An Im print of The Haworth Press, In c. Herbs, Spices, and Me di cinal Plants Ly le E. Craker, PhD Se ni or Editor Plall' Al kaloids: A Guide 10 Their DiscovelY and Distributi on by Robert F. Raffauf Herb s, S pi ces, and Medici nal Plams: Recent Advallces ill BolallY . Horticulture, alld Pharmacology. Volum es 1-4, edited by Ly le E. Craker and James E. Simon Related lilies of i nt erest from Food Products Press: Opillm Popp y: BotollY, Chemistry, and Pharmacology by L. D. Kapoor Th e HOll est H er bal: A Sensible Guide [0 the Use of Herbs and R el at ed Rem ed ies, Third Edition by V<lIT O E. Tyler Herbs ojC/lOice: 71!e 711erapelltic Us'e oj Ph ytomedici l/ a/s by ValTo E. Tyler Plant Alkaloids A Guide to Their Discovery and Distribution Robert F. Raffau f, FL S, FMAS Food Prodltcts Press An l!nprinl of The H<lwOrlh Press, Ine. New York . London Published hy . i" ood Pr oduels l'Tess, a~ imprint "fThe Haworth "r ess, 11I e 10 Alice Sired Binghamton, NY 13904·1580 t) 1996 by The Ilaworth Pr ess, li te. All righls reserved. No pm! of Ihis wurk n~ly be rCllfoduccd or IIli liz.:d in Any form Of by HII)' m eliUS, e!cC lronic 01 mech:Ulicnl. iuclutlillg phott)Cllllyilll!. micrufilm and recording, or by any illforn1aI,o'l slnragc al l<' rc tric~a l system, witho ll t permission in writ ing {Iu rn Ihe J)u bl i >h~r, J>ri n\ L'd in tlie Uniled SiDles uf Am errca. Ralfaur, n ober! F. (Koher! I'mucis). 1916- l)l~nl alkaloids 11 guide to t he ir discovery and dislri \)lIli on { Robe rt F. Rll ilnu f. p. em. Includ es hihliogmphical lclcrcnccs (p. ) ~nd i lideA . I SB N 1· 560 22 ·860· I (I lk. paper) I. Alkaloid s. 2. BQ(nn i cal chemislry.1. Til le. QKK9 8 .M IOS 1996 581.19'24 2ok20 90·5319 CII' CONTENTS Fo rewo rd VII Richard EVQ1ls Schultes Preface IX Alkaloid Test Results Appendix 225 Bibliography 229 Generic Index 23 1 ABO UT HIE AUTUOI! Rob e rt F. Ra ffauf , PhD , is Professor Eme ri tus of Phannacognosy and Medicinal Che mist ry at Nor theaste rn University in Boston. li e cu rrently hol li s an appointment as Research Associate at the Botani- ca l Museum of Harvard University, whe re he has al so tau ght Il c has served as Visiting P ro fessor at th e School of Ph ar macy at th e U ni versi ty of Pue rt o Ri co and al th e School of B io logical Sciences of lh e Na tional Polytechnic In stitute of Mexico. Dr. Ranilllf has led numerous expedit io ns in Ill a n y paris of th e wo rl d in the SC:U'C ~l f or n ew plants of pOI entia I medic in al value and has lectured ex ten SIve ly on thi s and related ma tt ers, in cluding th e rain forests and conserva- ti on. lie is th e author of eig ht books, 69 jo urnal pu blicat io ns, and four pate nt s, a nd he con ti nu es to work with graduate s tu de nt s i nt er- ested in natu ra l p ro ducts research. A 50-year member or th e Ameri- can Che mi cal Society, Dr. Ra fT a uf is < ll so a Fe ll ow of th e Li nncan Society of London and of th e American Associat ion of Advance- me nt of Science. In 1988, he was awar de d an appointme nt as Resi- de nt Scholar at the Rockefeller Study Center in Be ll agio, I ta ly. Foreword During scveral years of fi eld work in th e Nor th wcst A I ~lazon i ~, I li ved and worked with members of many of the AmaZO ni an In dian tribes. Il was an extrao rd inary opp0l1uni ty 10 obscl ve , apprcciat e, and record their local customs, rituals, and particularl y, as a botan ist , th e ir inte ll igent uses of th e plants of the fo rests in w hi ch th ey lived. The imp 0l 1a nce of lhis i nf ormation, beyo nd sim pl y creating an in te r- es tin g ethnobotan ie al record, was not en ti re ly obvio lL s at th e tim e. A fi cr my return to more acade mi c pursuit s, I met the author ·of th e fo ll ow in g pages, then a che mi st fo r II major North American pharmaceuti cal co mpnn y, with an interest primarily in th at portion of my notes d en ling wi th the treatme nt of disease as it WHS under- stood by th e Indian peo pl es. Some ph ill iS, it was though t, could be so ur ces of new che mi cal co mpo un ds lor cventual use in o ur ow n system of medicine. Furthermore, in (I n u t ~Clllpl t o reach that g? (l I, th e addition of che mi cal and phan naco loglc(li data to th c botalllcal record would expa nd our kn ow ledge of the ra in fo rest and its plant a mi < lIli mal inhabitants. A co ll abora ti on seemed a natural and log- ical consequence. As a resu lt of the work des cr ibed in th is book, many p la nts have been the subjects of further botanical, che mi cal, and phalmncologi- cal research. This integrated, interdisciplinary approach has been of gr ea t advantage to our students, thosc in my cO ~l rses at Harvard Un iversity as we ll as th ose of Professor Raffaul at t:'!0 11heaste rn Un iversi ty. A nu mber of our studen ts have even carncd out fi e ld wo rk in v ar iolls pa rt s of tr op ical A 1I1 erica. Wi th them we have been able to co-author a number of tec hn ic al papers on aspects of the wealth of natural resources in th e Weste rn Amaw ll a nd to sup pl y th em w ith cha ll en gi ng problems in th e numerous disciplines bear- in g on ra in forest sc ience. Toge th er we ha ve pub li shed two b oo ks (T he Healillg Forest, Ville 0/ tl i"e SO Il I) extending our kn ow ledge of th e biodivers it y of this vast area of So lith America. • 1'11/ PLANT ALKALOIDS It is Ollr hope that the inFonnation which my colleague has as~ se mbled here will cont inue to encourage academic as well as com~ mercial research on th e uselulncss of plants to humans and con trib~ ute to current efforts at conservation of Amazonian resources, some of which are on th e verge of extinction as a result of continued uncontrolled devastation in many areas of these marvelous forests. ~ Richard Evans Schultes. PhD. FMLS Jeffrey Professor of Biology. Emeritus Direc!OI; Botanical Museum, Harvard University, Cambridge, Massachusetts Preface The senrch for plant alkaloids ofnovcl chemical structure having potential va lu e as medicinal agents, as toxic principles, or as ap~ propriate starling materials for synthetic modification leading to other useful products, has occupied the attention of phytochemisls for over 150 years. In 19 50, about 2,000 of these substances were recognized; by 1970 this number had increased to about 4,000 and 20 years later 10,000 were known In recent times, th ey have been considered as uscthl taxonomic markers in attempts to constru ct more "natural" systems of plant classification through chemotax~ onomy, and as suitable substances for th e study of biosynthctic pathways in plant metabolism. During the laller part of the present century, emphasis on the conservation of plant resources and the e thl1 obotanical information concerning their use by many of the world's aboriginal societies has given added impetus to the imp or~ tance of the continued study of the "chemical factory," represented by the large unexploited portion of the plant kingdom before much or it disappear!> under the pressures incident to the mass movements of peoples and the increase in the world's p op ulation. Both li re in large part responsible for devastation of many nom s, particularly those of the rain forests. Not only will a number of species be lost even before they arc known and named by botanists, but litemlly thousands of chemical compounds new to sc ience will disappear forever. During the past 40 years I have been involved, in one way or another, with the screening of several thousand plants for th e presence of alkaloids as potential medicinal agents under th e auspices of a number of governmental, industrial, and academic institutions. Under~ ly ing this activity has been the hope thai the discovery of new eo m ~ pounds of this class would lead to substances at least as usefi .1 as tJlose which sim il ar studies have produced in the pasL. This screening ha s been done on lI ·esh plant material in the field, on small qu ant ities laken ix PLAN1'ALKALO/VS fmrn hcrbmium spec im cn s, and in th c labo ra tOty using a f ew grams of dricd male ri a lmad e available by bot.anists, colk"C tors, herb dcalers, and my personal co ll ections in many p <u1 S of th e wor ld . Va ri o ll s methods for the scr ee ning of largc num be rs of plant samplcs f or alkaloids have b ee n lI sed by many investigators more or l ess sliccessfully (Famsworth, 1966). Seve ml of thcse were used, depending on the faciliti es available at the time, but most o f th e results reported herein were ob tained by si mp lc methods described some years ago (R arTa uf , 1 962a; RafTauf and A lt schul, 1968). In the fi el d, th ese involve spoiling a droplet of plant s ap on filter paper and applyi ng a drop le t of Dmgc ndorfT's rcagcnt; the d evelo pment o f II red·onlll ge color iwJ icates the presence of alkaloids. In the laboral o· ry or h er barium, simplc ext r ac ts of dried plant mat er ial ma y bc used, with certain limitations, for th c samc purp ose (Balick, Ri vier, and Pl ow man, 1982). Methods may be adapted to needs of t he in ves ti gator; tests fo r somc speci fi c types of nitrogeno ll s co mpounds may be included (e.g .• in· dole s. simplc amines. and amino acids). All npprox im ation of th e quantity of a lk alo id in n sample may be made by co mpm ing th e intensity of the color produced in th c Dragendor fT test with th ose produced by standard alkaloid so lutions of kn ow n concentratio ll . fiy using the Dragc nd o rn ' fC.lgent as a spray, it is also poss ibl e 10 conduct thin- la yer chromatographic studies in the fi cl d. Several yt 'ars ago, in an a tt empt to devise a method for the idenlification of specific compounds in a p ar ticular alkaloid-positive co ll ection, 11 po l1 able laooratOlY was assembled for th e eva lu a ti on of sma ll extracts of fres h plant material by chromatograp hi c analysis using alumina-coated microscope slides and samples of the alkaloids expected to be presc nt. In the co urse of th e stud y, it was found that so me of th e compou nd s were prese nt on ly during a re:'i tlicted portion of the plant's growth cycle. We now kn ow that, in so me cases at least, alkalo id s are indeed further modi lied by th e plants t hnl produce th em. An advantage o f th ese simple methods is {I wt they a ll ow such studies to bc done far Irom a so urce of el ec tr ic power and other ame nities of lhe laboratory. But it is al so t me t hutt hcre arc a Ilumber of ullcertainties in such pro ce dur es; nol al! nitrogc l1 -eo ntni ni ll g sub- stances will react with either DragendortT's or Mayer' s reagen t. A ballery of test r eage nts wou ld give a more de fin itive although, even Pr e/act! then, not an i nf allible result (Ab isch and Reichstein, 1960). Fal ~c positi vc tests arc given by many Iyp es of n o ll a lk al~ idal plant co n ~ ht . uents with a variety of alkaluidal rcagents (H ab ib, ~980) . Ballck. Ri vier and Pl owman ( 1 982) have pointed ou t the Im po rtan ce of methods used in field dr y ing li nd pr ese rvation of herbar! um spec i· mens with respect to the rel iability of the re s ult ~ ob tamcd when tcsting them . A plea for such testing nnd a revt~w of the . n~ o re el ega nt methods for it s accomp li shment has been given. by Plllllp~ · son ( 1 982). Furlhe nn ore,lIs every plant co ll ector h as ( ll scove red, It is not always pr ac ti ca l in a given instan ce to co llect all of tl~ e p ar ts of a pl ant in which alkaloids may occu r. Nonetheless, an es timated 85 percent of nlkaloid ·co lltaining pl an ts can bc d~ t cc t c d by the methods described her e; a numb er of kn own a lk alO id al plants ha ve b ~e n in cluded in thc survcy to serve us controls. .' Il erbarium specimens repr ese nting othe rwise relati ve ly Ina cc e s· sible spec ics of severa l families (Apocy no ~eac, B o mba ~ a ceac, L~. copodiaceae, Lytliraceae, Orchidaceae, Rubtaceae) wc r ~ mdu d c, d III Ih is survey. Small s amples were sel ec ted fr ~)1 n sh ee ts III the. Gra~. Oakes Ames, and Arnold Arborctum herb<lna of Ilarvard Untvers~· ty und er the guidan ce of Prof essor Richard Evan ~ Sc hul~ es, E men - tus Dire ctor of the Botanical Mu seum, wh ose as sistan ce IS grateful· Iyacknow ledged. . Not all of this testing was done by m e; so me of It was don e by anthropologists, et hnobota ni sts, ~ Ild pl ,a llt col.l ec t ors in the cour se of field work sp onsore d by academiC or IIldU Sl rllll programs und~r .my directi on some by laboratory technicians under my su p c r v l s l~n , somc by ' fonner students as preliminary exerci~s i ll phy t oc helnl s· try, and some in co ll abora ti on wi th phyto chemical. programs sup- porl ed by the COli li cils of Sc ientific and lndus tnal Resenrch of Australia and So uth Africa. P or ti ons of the test r csu lts from these pm grams which had been at my disp osa l, I~ave b een i n cl ud e~ l h e. re for completen css in order to cO ll vey s ome Id ea of the alk al ?ld di S· tribution in plant fam il ies represented in the southern h e l ~ l s ph~re . Further data 0 11 these studies,.as well as the r es ults of the Isola ti on and pharmacological t es ting of a large n umber of nlkaloids, arc to be fOllnd in a r ccent exce ll e nt publication by the Melb ourne gro up (Co liins et aI., \ 99 0 ). [...]... multi/lol'llm, Agallosma O Uli/illata, A aganosma, A cOIyophyllata, A, cymostl, C A gracile, A /1Iarginata, A sch!echteriana, A velul;,w, AI/amanda spp (3), Alstonia macrophyl /a, A/ stonia spp (2), A/ yxia aCI//i/olia , A, aff/llis, A amOelltl, A miakel/sis, A bodinieri, A bracte%sa, A brevipes, A eael/milla, A celas/rilla , Alyxill cf de/oliala , Alyxia 19 cf plllle;, A cJllsiophyJ /a, A, dispJwemcarpa, A {~?ratophylla,... revo/uta, A, roma,tl1lijolta, 1' sc"'e~~1,­ teri, A scabrida, A scam/ells, A Selpelllllta, A slbuyalle,m , A sorgerensis, Alyxia '\PP (2), A srellala, A slfbaip;IIa, A torqueata, A, torresialla, A yunkullialla, Anchorllia sp., Allcylobothrys petersimw, Allgadellia berleri, A lil/denialla, Anodendmll , affine, A axillare, A bellflwmjaflllm, A, candolleallum, A corlOcelllll, A {aeve, A loheri, A /IIal1l1briafUIII... Aracium (= Crepis) loll/cmlWII, A asperijoJitl, A g /mu/Illosa A hieracioitles, Archibaccharis hine/ /a, A mllcronaw, A sescel1ticeps, A am/rogyna, Arclill'" lappa, Arctotis candida, A laevis, A pctiolaw, A swclwdijolia, Amica chamissonis, A cordi/olia , Artemesia mUllla A axillaris, Aspilia brachyphyllll, A carulhii , A " bsilllhlll1l, A fIIlstmlis, A balcJuw dru lJI , A dra cunclilus, A dllbia, A. .. {~?ratophylla, A, ellip/iea, A, ely /h rosperma , A j1oribullda , A forbesl/, A gfallco~ phylla, A Iwillallensis, A, iliei/olia , A intermedia, A lamii, A /at~I , A, laxij1ora, A levine;, A /el/cogyne, A Jillearifolia, A Illz(J "en'i~s, A microbllxus, A, mO lllieola, A myrtillae/olia, A mUII/mlllana, A oroplrila, A parvifolia, A, pisiform;s, A, pseu.d~sill.ellsis, A pur~ pur-eoc/ada, A reil/wardii, A revo/uta,... bellidiflora, Ageratum calldie/lflll , lilt/III A c;/aSS()ClII]1l1l1/ , A !tolls /ol/ioIlUm , A littorale, A IOllgi/o/il/lII, Agemtlllll spp (2), A /ol1lenlo.wl1I, Agiabampoa cOligesta, AgrialltJllIs empctrijoliwlI , Alberlil/ia brasiliensis, Afdall /a delliata, A/ om ;a wend/amlii, Ambrosia cOIiferlijiora, A polystachyia, A Irijida, Am//I ubium a/ ala, Allm:ycllls depresslIs, Allap/w/is cOlltorta , A lorentzii,... 112), Arc/otheco calendula (112), Arctotis " calllis, A Cllprea , A /eiocarpa, Arnica mOl/lata, Artemesia afra ( 112), A amilia, A calijornica (2 /3), A capillaris ' (1 12), A dOllglosiOlw, A drammcllioides, A indoricial/u, A k/otzchimw (1 /2), A mexical /a (214), Artemisia sp ( 1/2), Aspi/ia africalUI (2/4), Aster llethiopiclIS, A echillO/llS, A, hyssopi/olil/s, Aster \7)., A thallru'jo ji,scicllltlta... ludov;CiWlfI , A Pycllocephala, A rothrockii, Artemesia sp., A sleJ/(lrialln , A vlligaris, A. foliacea, A. foliosa, A helialllhoides, A lael'issillUl, A lillearifolia, A kotschy i, A mOlllevidellsis, A procilmbellS, A scll/III/;eri, A selosa, Aspilia ~pp (2), A verbeno/des, Asler ageralOities, A a/ p/tlIIS, A bakeriallm", A carnlial/II.,', A cordijo!illS A declllllhem', A di varica/II:", A ericaejo!ills, A exilis,... Aralia mcelllosa ( 1/4), Clissollia pal/icll/ala, C thyrsiflora, C 11111bellijera ( 1/3 ), Dendrop(lIIax peJl/lcipllllclata (115), Didymopwwx rremllllllll (112), Gasrol/ia pap"tllla, SeemaJmtlralitl gerrardii The foll owing species were negative: Acalllhopallax Irijoliallls, Aralia cali/arnica, A hispida, A /Iumilis, A l/IulicallJis, A regelia/la, A spinosa, AstIVtricha asperijoJia, A jlocosca, Bra,~·.\'{lia... ("·Ol/il/Illll, H paplJ(lIla l-Ioodill sp., Kal/(lhia JallijIora ( 1/2), Marg(lrelta rosea, Mar.wJel/ia dregei M ros,rrala , Micr%ma iI/callum, M massollii M saggitalwlI (112), PachycQ/1JUS rigida P salber Peclillaria brevi/oba, Pelliarrhillum illSipidlllll, Perglllaria daemia-extensa (3/1 0), Pelgu/aria sp., Secamolle gal'al'dii, SlapeJia giganlea (2/3), S oJivacea , S schillZii, Slapelia sp., Toxocal '- s The... c(llladellse A tell/ollii, A laitoellse PIIS wriglttimws, Tylophol 'a l/laC/'ophylla, 'I: ovata, Xysma/obilllll ulldlllallllll The fo llow ing species gave negative tests: Arlll!iia serico/era , Asclepias albicallS, A ampfexicalllis, A allgustijiJlia, A oW'iculalll, A bidclIJata, A bmchysJep/wllia, A burchellii, A cali/ol'lliclI , A cOlltrayerba, A fililol'l/!is, A gibba, A glaberl'i1l1(1, A glal/cesceliS, . multi/lol'llm, Agallosma OC Uli/illata, A. aganosma, A. c OIy op hyllata, A, cymostl, A. gracil e, A. /1Iar ginata, A. sch!echteriana, A. velul;,w, AI/amanda spp. (3), Alstonia macrophyl /a, . slfbaip ;IIa, A. torquea- ta, A, torresialla, A. yunkullialla, An chorllia sp., Allcylobothrys pet- ersimw, Allgadellia berleri, A. lil/denialla, Anodendmll , affine, A. axillare, A. bellflwmjaflllm,. macrophyl /a, A/ stonia spp. (2), A/ yxia aCI//i/olia, A, aff/llis, A. amOelltl, A. miakel/sis, A. bodinieri, A. bract e%sa, A. brevipes, A. eael/milla, A. celas/rilla, Alyxill cf. de/oliala,