NATURAL PRODUCTS the secondary metabolites

1. NATURAL PRODUCTS thesecondarymetabolites

2. Prof. Dr. Nezhun GÖREN Yıldız TechnicalUniversity Faculty of ScienceandArts Department of MolecularBiologyandGenetics Istanbul / Turkey

3. SYSTEMATICS OF LIVING ORGANISMS • Biologistsestimatethatthereareabout 30 millionspecies of livingorganismsinhabitingthisbiosphereandonly a millionandhalf of it havebeendiscoveredanddescribedso far. • Thespecies of plantsandanimalsidentifiedso far exhibit a greatvariation in their form, structureandmode of life. • A systematicstudy of theselivingorganisms is possibleonlywhentheyaregroupedintosmallerentitiesbased on theirsimilaritiesanddifferences. • Thebranch of biologyconcernedwithclassification of livingorganisms is calledsystematicsandthebranchthatdealswithdescriptionandnaming is calledtaxonomy.

4. Thehistory of classificationcouldbe viewed in 6 phases • PHASE 1. ANCIENT CLASSIFICATIONS and MIDDLE AGES • PHASE 2. THE HERBALISTS : RENAISSANCE • PHASE 3. THE EARLY TAXONOMISTS • PHASE 4. LINNAEUS AND HIS APOSTLES • PHASE 5. PHYLOGENETIC SYSTEMS • PHASE 6. MODERN SYSTEMATICS

5. HISTORYPHASE 1. ANCIENT CLASSIFICATIONS

6. CHINA • CHINA is famousforitstraditionalherbalmedicinethatdatesbackthousands of years.  • DuetothelegendEmperorShenNungwasthefounder of Chineseherbalmedicine. He composedtheShennongpenTs’aochingorGreat Herbal in about 2700 BCE as theforerunner of alllaterChineseherbals. • There is a copy of it made c. 500 CE anddescribesabout 365 herbs.

7. INDIA • Traditionalherbalmedicine of India, known as Ayurveda, possiblydatesbacktothesecondmillennium BCE tracingitsoriginstotheholy Hindu Vedasand, in particular, theAtharveda.  • Theearliestsurvivingwrittenmaterialis theBowerManuscript—datedtothe 4th century CE. • Otherearlyworks of AyurvedaincludetheCharakaSamhita, attributedtoChakara. Thistradition, however is mostly oral.

8. EGYPT and MESOPOTAMIA • Byabout 2000 BCE, medicalpapyri in ancientEgyptincludedmedicalprescriptionsbased on plantmatterial. • TheancientEgyptianPapyrusEbers is one of theearliestknownherbals; it datesto 1550 BCE. • TheearliestSumerianherbaldatesfromabout 2500 BCE as a copiedmanuscript of the 7th century BCE. • WrittenAssyriantabletsdated 668–626 BCE, andlistabout 250 vegetabledrugs: thetabletsincludeherbalplantnamesthatarestill in usetodayincluding: saffron, cumin, andsesame. 

9. GREECE • TheancientGreekscollectedmuch of theirmedicinalknowledgefromEgyptandMesopotamia. • Firststudies on animalswere done bytheGreekphilosophersHippocrates (460-377 BCE) andDemocritus (460-370 BC). • Hippocrates, the "father of medicine" (famousfortheHippocraticoath), usedabout 400 drugs, mostbeing of plantorigin. • Hippocratesthoughcountedtheanimalspecies, he didn’tclassifiedthem. HippocratesandDemocritusPalaisdesBeaux-Arts Lille

10. Aristotle (384–322 BC) • Thefirstclassification of livingorganismswere done byAristotle. • Currentsystems of classifyingforms of livingbeingsdescendfromthethought of theGreekphilosopherAristotle. • He published his works in his book “Metaphysics”. This is thefirstknownclassification of "beings".

11. AristotleclassifiedthelivingbeingsduetotheirphysiognomyandtheirenvironmentAristotleclassifiedthelivingbeingsduetotheirphysiognomyandtheirenvironment PLANTS • Herbs • Shrubs • Trees ANIMALS • Thosewholive in air • Those who live on land • Those who live in water Aristotle'sclassificationwaseventuallyoutdatedbyadditionalknowledgeandforgotten.

12. Theophrastus (370-285 BC) • Theophrastus, a student of Platon andAristotle, knownas “thefather of botany, since he wasthefirsttowritedown a classification in a permanentandlogical form. • He wrote a classification of all known plants of the time, De HistoriaPlantarum, which containsabout 480 taxa, usingprimarilythemostobviouscharacteristics of grossmorphology. • We still recognise many of his plant genera, like Narcissus, Crocus and Cornus. • SeveralnameswhichTheophrastusused in his book, latertakenupbyLinnaeus in his book “GeneraPlantarum”, andtheyareused in thesame sence today as well. • De HistoriaPlantarumwas used fortaxonomic purposes until the Middle Ages in Europe.

13. DioscoridesPedanius(1st century AD) • Dioscoridesalso a Greek, was a physician in the Roman armyandthereforeinterested in themedicinalproperties of plants. • He describedabout 600 taxa in his book “De MateriaMedica”, largelyfromthefirst-handobservation, anddetailedtheirusefulapplications. • His bookwasarranged in a lessorderlymannerthanthat of Theophrastus, but nevertheless it becamethestandardreferenceworkforover a millenium, andwas not supersededuntilthe 16thcentury. It can be consideredthefirstherbal.

14. Dioscorides',  De MateriaMedica, Byzantium, 15th century. Arabic Book of Simple Drugs (c. 1334) from Dioscorides’ De MateriaMedica. By Kathleen Cohen, in theBristishMuseum. Arabic translation of the MateriaMedicaby Dioscorides

15. Dioscorides',  De MateriaMedica, The SüleymaniyeLibrary, Istanbul, Turkey

16. Dioscorides',  De MateriaMedica, The SüleymaniyeLibrary, Istanbul, Turkey

17. Dioscorides',  De MateriaMedica, The SüleymaniyeLibrary, Istanbul, Turkey

18. MIDDLE AGES • Abü I-WalidMuhammad bin Ahmad bin Rüshdcommonlyknown asIbnRsuhdorby his Latinized name Averroes (1126-1198), was an AndalusianMuslimpolymath, a master of Aristotelianphilosophy, Islamicphilosophy, Islamictheology, Maliki lawandjurisprudence, logicpsychology, politicsandAndalusianclassicalmusictheory, andthescience of medicine, astronomy, geography, mathematics, physicsandcelestialmechanics. • The 13th-century philosophicalmovementbased on Averroes' work is calledaverroism. • TheMuslimjudge of SevilleIbnRushd, translatedthebook of Aristotle, Anime (Animals) in 1172. Thisbookwaslatertranslatedto Latin byMitchcelltheScot. • Through MiddleAgesnewwrittenbooks on botanywererareandlargelybased on those of theancientGreeks.

19. PHASE 2. THE HERBALISTS : RENAISSANCE

20. TheancientGreeksand Romans namedandclassifiedorganisms, particularlywhichwereusefultothem. • Theyhad namesformedicinalplantsandfortheanimalstheyhuntedandthosethattheyfeared. • Thistraditionwascarried on in northern Europe, wherethenaming of plantswas done byherbalists. • About at thesame time, in thelate 16thcentury, thescience of scientificnamingstarted. • Plantsandanimalsweregivenlong, polynomial Latin names. At that time Latin wasthelanguage of scholarship. • Forexample, thehumbletomatowasgiventhepolynomialLatin name : Solanumcauleinermiherbaceo, foliispinnatisincisiswhichmeansthe'solanumwiththesmoothstemwhich is herbaceousand has incisedpinnateleaves.'

21. Inthe 16thcentury, peopleworkingwithplantsandanimalsstartedtryingto name themformally, andtousethosenamesconsistently. Thisbecameincreasinglyproblematic as diversityincreased. • Initially, onlylocalorganismswereknown but as otherlands, such as the New World werediscoveredandexplored, thesystembecamecomplicated. • Forexample, some of theJesuitpriestswhoaccompaniedPizarrowhen he conqueredtheIncaempiredecidedthattheremusthavebeentwogardens of Eden becausethevegetableproductions of theAndesweresoverydifferenttothose of Spain. • Manysimilartheoriesabounded at the time because it wasdifficulttoexplainthediversitybeingencounteredusingtheBiblicalparadigm.

22. Theinvention of printing in Renaissance in Europeenablednewbooksto be produced in largenumbers. Thefirstbooks in thefield of botanyweretheherbals. Inthosedaysbotanywasactuallysynonymouswithherbalism. Thestudy of theusefulplants, particularly as foodsandmedicine, andtheherbalistsdominatedthe 16th centurybotanicalworld.

23. AZTECS • An illustratedherbalpublished in Mexico in 1552, Libellus de MedicinalibusIndorumHerbis ("Book of MedicinalHerbs of theIndies"), is written in theAzteclanguageby a nativephysician, Martin Cruz. • Europeanssuggestthattheywerefollowingthetraditions of theirSpanishmastersratherthan an indigenousstyle of drawing. 

24. PHASE 3: THE EARLY TAXONOMISTS

25. Theadvent of microscopesandthediscoveryof microorganisms in 17thcenturynecessitated a thoroughmodification in thesystem of classification. • Towardsthe 17th centurytaxonomic works became original enough to replacethe ancient Greek works. • The reasons for this was • the development of optic lenses, which made it possible to study details in the different species, • collection of specimens became part of the growing sciences, • the emphasis turned from medical andnutritiveaspects to taxonomic aspects.

26. AndreaCaesalpino(1519-1603) • An Italian, has beencalledthefirstplanttaxonomist, since he classifiedtheplantsscientificaly. • His bookDe Plantis (1583), classifiesabout 1500 species. He is thepioneer of scientifictaxonomy. • His classification was based on growth habit together with fruit and seed form, as was that of Theophrastus. • Some groups that he recognized we still acknowledge, like the plant families Brassicaceae and Asteraceae. • His classificationlookedlikethecrudeclassifications of Theophrastusratherthantheartificialsystem of herbalists.

27. TheBauhinbrothers; Jean Bauhin (1541-1631) andGaspardBauhin (1560-1624) TheBauhinbrothers; JeanBauhinandGaspardBauhin, alsocalledCasperBauhinSwissbotanists.

28. Theyworkedseparately but rather in similarlines. • CasperBauhinphysician, anatomist, andbotanistwhointroduceda scientificbinomialsystemof classificationtobothanatomyandbotany. • He not onlydescribedandclassifiedallthe 6.000 species, but alsolistedtheirsynonyms, which was a great necessity of the time.Thusthecaoticnomenculaturewasbrought in order. • ThebookPinaxTheatriBotanici (1623) by G. Bauhin is a landmark of botanicalhistory. • Bythis time, specieswereknownwithmanydifferentnames in differentbooks, andPinaxTheatriBotanicimade a welcomeorder in thetaxonomicworld.

29. GaspardBauhin (1560-1624) • Theclassificationsystemwas not especiallyinnovative.Heusedtraditionalgroupssuch as "trees", "shrubs", and "herbs", andothercharacteristicssuchutilization, forinstancegroupingspicesintotheAromata. • He didcorrectlygroupgrasses, legumes, andseveralothers. • His mostimportantcontributionwas in thedescription of generaandspecies.  • He recognisedgeneraandspecies as majortaxonomiclevels, andusedbinarynomenculature. Thus, Bauhin’sPinaxforetoldLinnaeus’ greatwork. • He introducedmanynames of generathatwerelateradoptedbyLinnaeus, andremain in use. • He separatedbotanyfromMateriaMedica. • CarolusLinnaeusnamedthegenusBauhinia (familyCaesalpiniaceae) forthebrothers Johann andGaspardBauhin.

30. John Ray (1627-1705) • Theearliestattempttowards a naturalsystemcamefrom John Raywhogave a detaileddescription of about 18.000 types of plants. He alsointroducedtheconcept of species. • A moresystematicandscientificsystemcallednaturalsystem of classificationemerged. Itwasbased on specificsimilaritiesanddifferencesbetweenorganisms. • His mostimportantcontributionwastheestablishment of species as theultimateandconcreteunit of taxonomy.

31. Althoughgenusandthehighertaxonomicunitsareabstractconcepts, species is a concreteconcept, andthewholetaxonomiccategoriesbased on thisunit.

32. J.P. de Tournefort(Joseph Pitton de Tournefort) (1656-1708) • A French physicianand a famousbotanistconstructed a botanicalclassificationthatcametorule in botanicaltaxonomyuntilthe time of Carl Linnaeus. • He collectedplantsandcreated a plantcollection. His classificationsystembased on floralcharacters. He usedforthefirst time thecorollaproperties of theflowerstoclassifythem. He accepted “genus” as a basicunit. He classifiedabout 9.000 species. • Tournefort’ssystemwasusedby C. Linnaeus as a youngstudent. LaterLinnaeusbased his system on thesexualsystem, whereasTournefort had alwaysdeniedthe presence of sexuality in plants. • TheWord herbariumalsoseemstohavebeen an invention of Tournefort.

33. PHASE 4. LINNAEUS AND HIS APOSTLES

34. CarolusLinnaeus(1707-1778) • Alsoknown as Carl vonLinnéwas a Swedishbotanist, physician, andzoologist. He wasborntwoyearsafter John Ray’sdeath. • Many of his writingswere in Latin, and his name is translated in Latin as Carolus Linnæus (after 1761 Carolus a Linné). • CarolusLinnaeusand Charles Darwinarethetwoscientistswhomadethebiggestimpact on biology.

35. He was one of the most admiredscientists in Europe. • The Swiss philosopher Jean-Jacques Rousseau sent him the message: "Tell him I know no greater man on earth." • The German writer Johann Wolfgang von Goethe wrote: "With the exception of Shakespeare andSpinoza, I know no one among the no longer living who has influenced me more strongly." • Swedish authorAugustStrindberg wrote: "Linnaeus was in reality a poet who happened to become a naturalist". • Among other compliments, Linnaeus has been called  • Prince of Botanists, • "The Natural History of the North," • "The Second Adam".

36. Linnaeus is commonlydescribed as "Father of Modern Taxonomy" for his contributions. • Linnaeus’ main contributionwastobringordertothemixed-uparray of literatureandsystem of classificationwhichthe 17th centurybotanists had confronted. • He classifiedlivingorganismsintotwokingdoms, • Plantae (plants) • Animalia (animals).

37. LINNAEUS’ CLASSIFICATION SYSTEM • Linnaeusdeveloped his classificationaddinggenus, order, andclassgroups. • He recognisedspecies as thebasicunit of classificationandimplementedtheuse of fourspecificcategories • class • order • genus • species

38. Linnaean Classification System has seven different levels. From smallest to largest, the levels are species, genus, family, order, class,phylum, and kingdom. Each of the ranking levels is called a taxon. Just as ; A genus is a group of similar species, A family is a group of similar genera, An order is a group of similar families, A class is a group of similar orders, A phylum is a group of similar classes, A kingdom is a group of similar phyla.

40. Linnaeusclassifiedplantsaccordingtosexualsystemof plants, which was an artificial classification based on the sexual parts of the flowers: the stamens and pistils. • Thissystembased on thegenitalorgans of theflowers, such as flowerswith 1 stamen, with 2 stamens, orflowerswith 1 stamenand 1 pistilandso on, whichcould be observedwithnakedeyes. • In a time when people debated whether plants had sexuality or not, this suggestion more or less shocked the scientific world. • However, the practical use of the system and Linnaeus’ careful observations persuaded the critics and Linnaeus sexual system of plants became the highest fashion also outside the scientific community.

41. How does Linnaeus’s system of classification help establish the unity of life ? • The system classifies organisms based on overall similarities and differences to one another. • Organisms in the same genus share many similarities. • Organisms in the same kingdom may have many differences, but they still have common traits with one another.

44. LINNAEUS’ NOMENCULATOR AnothersignificantcontributionfromLinnaeus is thesystemof binomialnomenclature. He gavesientificnamestoeachplantandanimalspecies. In the 1730s, Carolus Linnaeus developed a naming system, called binomial nomenclature. In binomial nomenclature, each species is assigned a two-part scientific name: • The first name refers to the genus. • The second name refers to its species, which is chosenbytheauthor. • These name must be writtenitalicandthefirst name mustbeginwithcapitalletter, andthesecond name must be written in smallletters. • Itmust be followedbyauthor’s name. • Thisis thenomenculaturewhichweusetoday is essentially his.

45. Instead of phrasenames he usedthebinomialnames. Forexample: • He usedNepetacatariaL.instead of ‘’Nepetafloribusinterruptespicatusredunculatis‘’. • Thebinary form of species names called "trivial names" for both plants and animals. • Bythe time of Linnaeusthesituationwasreallybad. Linnaeuscounted 8530 species of floweringplants in 1753. • Thesimplicity of Linnaeus' trivialnamesrevolutionizednomenclature, andsoonbinarynomenclaturecametoreplacethephrasenames. • Today, everyplantoranimal name publishedbefore1753 or 1758, is called "prelinnaean" andis not valid. • AlsoearlynamespublishedbyLinnaeushimselfare "prelinnaean"!  

46. Thisbinarynomenclature, withwhichLinneaus is usuallycredited, wasfoundedbyBauhinmorethan a centurybeforeLinnaeus. • BinomialswerequiteoftenusedbyG.Bauhin in his Pinax (1623) over a centuryearlier, so it is not trueto say thatLinneaeusdevisedthesystem. • However, C. Linneaeuswasthefirstscientistwhoused an additional, convenient name foreveryspecies in SpeciesPlantarumwhichledtotheireventualuniversaladoption, andnowadaystheyaremandatory.

47. Bymeans of thebinomialnomenculator, theplantscould be definedwhich had not beenableto define before. He classifiedtheplantsduetotheirsimilaritiesanddifferences. • BeforeLinnaeus, thedescription of eachspecieswas in the form of phrase-names of uptotwelvewords, startingwiththegeneric name. • Thephrase-namesconsisted of severaldifferentwords, containingsomedescriptiveadjectives. • Thescientistscouldusedifferentnamesforthesamekind of species. • Thisnomenculaturecausedlots of disorderandconfusion. • TheLinnaeus’ nomenculatorsystembrought a standizationandeasilyunderstandible form of description.

48. For nomenclatural reasons two works of Carl Linnaeus are regarded as the starting points of modern botanical and zoological taxonomy: • the global flora Species Plantarum, published in 1753, • the tenth edition of SystemaNaturaein 1758 including global fauna. • The reason for this is that Linnaeus introduced in these books a binary form of species names called "trivial names" for both plants and animals.

49. CONCLUSION • With the works of Linnaeus, botany and zoology transformed into a Scientia, a science surrounded by philosophy, order and systems. • Until then, these two disciplines had merely been a sub-branch of practical medicine built on disordered observation of different species. • Althoughthissystemwas popular because of itssimplicity, it didn’tshowtherelationshipsbetweenthelivingorganisms. TheSexualSystemwasartificial.

50. Linnaeushimselfwasfullyaware of this. Howeverscientistwere not knowingtheevolution yet.