制藥工程-專業(yè)英語-Unit-1

TheprofessionalEnglishofpharmaceuticalengineeringWangXinliangEastChinauniversityofscienceandtechnology13.02.2012FinalexaminationTwoparts:gradeofdailystudy(30%)attendanceratehomeworkothers(exercise,middleexamination)gradeoffinalexamination(70%)ThecontentofexaminationThecontentofexaminationDegreetest

50%basicEnglish

50%professionalEnglish

word:translationfromEnglishtoChinese(5points)translationfromChinesetoEnglish(5points)Translation:(40points)4paragraphswhichincludeabout250wordsineachofthem.payattentiontoonly125to150wordsineachparagraphneedtobetranslated.These4paragraphsarenotsimplesentence.HowtolearntheprofessionalEnglishMastersomeskillsMasterthenecessaryknowledgeWhatisthemostimportantthingmorereading,morespeaking,morewritingWhatistheimportantthinginthiscourseremembertheword?translatesentencebysentence?learnmoreprofessionalknowledge?YoudaoDict有道詞典HowtoteachtheprofessionalEnglishCrocinyellow（藏花素）,whichisextractedfromGardeniajasminoidesEllis（梔子）,iswidelyusedasanaturalfoodcolorantinAsiancountries,whileGardeniaextracthasbeenusedinChinesetraditionalmedicine(CTM)forcuringanumberofailments[3].Thesecrocetin（藏紅花酸）derivatives,whicharedifferentfrommostfamiliesofcarotenoids（類胡蘿卜素）,areknownfortheircoloringpropertiesowingtotheirpeculiarwater-solublebehavior[4].Numerousstudieshavedealtwiththecomponentstructuresofyellowpigmentextractsisolatedfromgardeniafruits[4–8],theirspectroscopiccharacterizationandradical-scavengingactivity[4,9],dataconcerningtheconcentrationofmajorcomponentsforthedeterminationofoptimaltimeofharvestandextractionprocess[10,11].ThecontentofthiscourseIntroducesomeskillsoftranslationanddosomeexerciseintheclassroom.SummarizesomeregulationsintheprofessionalEnglish.Learnthetext.Discusssometopics.Part1MedicinalchemistryUnit1ProductionofDrugsThewholeconceptoftheproductionofdrugsTheclassificationofthedrugsTheintroductionofeachgroupofdrugs

Thefirstquestion:howtoclassifythedrugDependingonthekindsofdisease:CardiovasculardrugsDigestivesystemdrugsRespiratorysystemdrugsAntiviraldrugsProprietarydrugsorGenericdrugsDependingontheproductionororigin:藥品的生產(chǎn)依據(jù)其生產(chǎn)或來源，藥物制劑可以分為三類：I.完全的合成材料（人工合成材料），II.天然產(chǎn)物，和III.源自部分合成的產(chǎn)品（半合成產(chǎn)品）。

Dependingontheirproductionororiginpharmaceuticalagentscanbesplitintothreegroups:I.Totallysyntheticmaterials(synthetics)，II.Naturalproducts，andIII.Productsfrompartialsyntheses(semi-syntheticproducts).Unit1ProductsofDrugsWordssyntheticsglycoside(s)hydrolysatedextrantargetedmodificationEpinephrineLevodopaProstaglandinsD-PenicillamineVincamineEukaryontProkaryontLeuconostocmesenteroidesCorynebacteriumglutamicumBrevibacteriumflavumPropionibacteriumshermaniipurinanucleotidecitricacidmonosodiumL-glutamatechromatinn.[用作復(fù)]人工合成(絕緣)材料n.配醣；配糖體；糖苷n.水解液；水解產(chǎn)物n.葡萄聚糖；右旋糖酐定向（或靶向）修飾n.腎上腺素n.[藥]左旋多巴（等于L-dopa）n.前列腺素（prostaglandin的復(fù)數(shù)形式）n.D-青霉胺n.長春胺n.真核細(xì)胞n.原核細(xì)胞腸膜狀明串珠菌谷氨酸棒桿菌黃色短桿菌謝氏丙酸桿菌嘌呤核苷（酸）檸檬酸谷氨酸鈉（味精）n.核染色質(zhì)；核染質(zhì)AlkalimetalLilithiumNasodiumKpotassiumRbrubidiumCscaesiumFrfranciumHhydrogen本書的重點(diǎn)是在于Ⅰ和Ⅲ類中最重要的化合物——藥物合成。但是，這并不意味著，天然產(chǎn)品或其他制劑并不太重要。它們可以作為有價(jià)值的先導(dǎo)結(jié)構(gòu)，他們常常作為重要的合成產(chǎn)品的起始原料或中間體產(chǎn)品。

表1列出了獲取藥物制劑的不同方法的概述。

TheemphasisofthepresentbookisonthemostimportantcompoundsofgroupsIandⅢ-thusDrugsynthesis.Thisdoesnotmean，however，thatnaturalproductsorotheragentsarelessimportant.Theycanserveasvaluableleadstructures，andtheyarefrequentlyneededasstartingmaterialsorasintermediatesforimportantsyntheticproducts.Table1givesanoverviewofthedifferentmethodsforobtainingpharmaceuticalagents.

最初從天然資源庫獲得的幾個(gè)重要治療作用的天然產(chǎn)品，今天可以通過全合成更有效地，例如更經(jīng)濟(jì)地被制備出來。這樣的例子包括L-氨基酸、氯霉素、咖啡因、多巴胺、腎上腺素、左旋多巴、肽類激素、前列腺素、D-青霉胺、長春胺，以及幾乎所有的維生素。

Severaltherapeuticallysignificantnaturalproductswhichwereoriginallyobtainedfromnaturalsourcesaretodaymoreeffectively-i.e.moreeconomically-preparedbytotalsynthesis.SuchexamplesincludeL-aminoacids,Chloramphenicol,Caffeine,Dopamine,

Epinephrine,Levodopa,peptidehormones,Prostaglandins,D-Penicillamine,Vincamine,

andpracticallyallvitamins.

在過去的幾年里，發(fā)酵，即微生物過程，變得極其重要。通過現(xiàn)代技術(shù)和基因選擇導(dǎo)致的微生物的高性能突異變種的結(jié)果，發(fā)酵已成為選擇寬范圍物質(zhì)的方法。真核細(xì)胞（酵母菌和霉菌）和原核細(xì)胞（單細(xì)胞細(xì)菌，放線菌）都可用作微生物。可以得到下列產(chǎn)品類型：

Overthelastfewyearsfermentation-i.e.microbiologicalprocesseshasbecomeextremelyimportant.Throughmoderntechnologyandresultsfromgeneticselectionleadingtothecreationofhighperformancemutantsofmicroorganisms,fermentationhasalreadybecomethemethodofchoiceforawiderangeofsubstances.BothEukaryonts(yeastsandmoulds)andProkaryonts(singlebacterialcells,andactinomycetes)areusedmicroorganisms.Thefollowingproducttypescanbeobtained:

盡管從諸如腸膜狀明串球菌的某些微生物的黏膜可以生產(chǎn)葡萄聚糖，但第2和3類產(chǎn)品類型只與藥品生產(chǎn)的有關(guān)。葡聚糖自身的分子量5萬?10萬，可用作血漿代用品。而來自谷氨酸棒桿菌和黃色短桿菌突變體的初級(jí)代謝產(chǎn)物中，L-氨基酸尤其令人感興趣。從這些生物體中，可以生產(chǎn)約35萬噸L-谷氨酸單鈉鹽（味精，食品添加劑）和約70,000噸L-賴氨酸（用于植物蛋白補(bǔ)充物質(zhì)）。此外，重要的初級(jí)代謝產(chǎn)物還有嘌呤核苷酸、有機(jī)酸、乳酸、檸檬酸和維生素，例如源自謝氏丙酸桿菌的維生素B12。

Disregardingtheproductionofdextranfromthemucousmembranesofcertainmicroorganisms，e.g.Leuconostocmesenteroides,classes2and3

are

therelevantonesforthepreparationofdrugs.Dextranitself,withamolecularweightof50,000~100,000,isusedasabloodplasmasubstitute.AmongtheprimarymetabolitestheL-aminoacidsfrommutantsofCorynebacteriumglutamicum

andBrevibacteriumflavum

areespeciallyinteresting.Fromtheseorganismssome350,000tonesofmonosodiumL-glutamate(foodadditive)andsome70,000tonesofL-lysine(supplementforvegetableproteins)areproduced.Furtherimportantprimarymetabolitesarethepurinanucleotides,organicacids,

lacticacid,citricacid,andvitamins,forexamplevitaminB12fromPropionibacteriumshermanii.

在次生代謝產(chǎn)物中首先必須提到的是抗生素。以下五組藥品代表了全球每年價(jià)值170億美元：

青霉素類（產(chǎn)黃青霉），

頭孢菌素類（頂頭孢霉菌），

四環(huán)素類（金霉素鏈霉菌），

紅霉素類（紅霉素鏈霉菌），

氨基糖苷（如來自灰色鏈霉菌的鏈霉素）。

Amongthesecondarymetabolitestheantibioticsmustbementionedfirst.ThefollowingfivegroupsrepresentayearlyworldwidevalueofUS-$17billion:penicillins(Penicilliumchrysogenum)，cephalosporins(Cephalosporiumacremonium)，tetracyclines(Streptomycesaureofaciens)，erythromycins(Streptomyceserythreus)，aminoglycosides(e.g.streptomycinfromStreptomycesgriseus).Dextranisapolymerofglucose.Itisawhitepowderanditissolubleinwaterandinsolubleinethanol.Dextrancanincreasetheplasmavolumeandmaintainthebloodpressure,soitcanbeusedforasabloodplasmasubstitute.Itcanbeproducedbyfermentationofsucroseinleuconostocmesenteroides.Certainly,thefermentationonlyproducetherawmaterialandthesomepurificationisnecessary.

ThesimpleintroductionofdextranMolecularformula:（C6H10O5）nglucose葡萄糖fructose果糖

mono-,di-,tri-,polymer單體，二聚體，三聚體，聚合體(物)sucrosen.蔗糖

從微生物中已分離出約5000種抗生素，但其中只有不到100種有治療用途。但是，必須記住，許多衍生物已通過部分合成法來修飾以獲得治療用途；在過去的十年里，采用半合成方法已從?-內(nèi)酰胺獲得了約50,000種制劑。發(fā)酵是在體積高達(dá)400m3的不銹鋼發(fā)酵罐中進(jìn)行。為了避免受到噬菌體等微生物的污染，（發(fā)酵）全過程都必須在無菌條件下進(jìn)行。由于更重要的是，發(fā)酵只在有氧條件下才能發(fā)生；因此，需要提供有足夠量的（無菌）氧氣或空氣。二氧化碳的來源包括糖類（碳水化合物），如廢糖漿、低聚糖類和葡萄糖。

About5000antibioticshavealreadybeenisolatedfrommicroorganisms,butoftheseonlysomewhatfewerthan100areintherapeuticuse.Itmustberemembered，however，thatmanyderivativeshavebeenmodifiedbypartialsynthesisfortherapeuticuse;some50,000agentshavebeensemisyntheticallyobtainedfrom?-lactamsaloneinthelastdecade.Fermentationsarecarriedoutinstainlesssteelfermentorswithvolumesupto400m3.Toavoidcontaminationofthemicroorganismswithphagesetc.thewholeprocesshastobeperformedundersterileconditions.Sincethemoreimportantfermentationsoccurexclusivelyunderaerobicconditions,agoodsupplyofoxygenorair(sterile)isneeded.Carbondioxidesourcesincludecarbohydrates,e.g.molasses,saccharides,andglucose.Wordsammonium（ammonia）aminesodiumbicarbonatesodiumhydroxidehydrochloric/sulfuric/nitricacidhypochloritechloritechlorate

perchloratenitritenitratesulfidesulfitesulfate

persulfatephosphitehypophosphite

phosphatedihydrogenphosphatehydrogenphosphate銨；銨鹽（氨；氨水）胺碳酸氫鈉；小蘇打、NaHCO3氫氧化鈉、NaOH鹽酸；硫酸；硝酸次氯酸鹽（酯）亞氯酸鹽（酯）氯酸鹽（酯）高氯酸鹽（酯）亞硝酸鹽（酯）硝酸鹽（酯）硫化物；硫醚亞硫酸鹽（酯）硫酸鹽（酯）過硫酸鹽（酯）亞磷酸鹽（酯）次磷酸鹽（酯）磷酸鹽（酯）磷酸二氫鹽磷酸一氫鹽Prefix----------Parent-----------SuffixNomenclatureofparentpart:NomenclatureofalkanesandalkylsubstituentsStraight-chainalkanes

Straight-chainalkanesarenamedbycountingthenumberofcarbonatomsinthechainandaddingthefamilysuffix-ane.Thuspentaneisthefive-carbonalkane,andhexaneisthesix-carbonalkane.NomenclatureofOrganicCompounds1Analkylsubstituent(oranalkylgroup)isanalkanefromwhichasinglehydrogenhasbeenremoved.Alkylsubstituentsarenamedbyreplacingthe“ane”suffixofthealkanewith“yl”.Theletter“R”isusedtoindicateanyalkylgroup.ThusCH3-hasthenameofmethyl,whilethegroupofCH3CH2-wasnamedethyl.NumberMolecularNameNameinAlkylofcarbonsformulaChinesesubstituents1 CH4 Methane

甲烷

Methyl

2 C2H6 Ethane

乙烷

Ethyl3 C3H8 Propane

丙烷

Propyl4 C4H10 Butane

丁烷

Butyl5 C5H12 Pentane

戊烷

Pentyl6 C6H14 Hexane

己烷

Hexyl7C7H16 Heptane

庚烷

Heptyl8 C8H18 Octane

辛烷

Octyl9 C9H20 Nonane

壬烷

Nonyl10 C10H22 Decane

癸烷

Decyl11 C11H24Undecane

十一烷

Undecyl12 C12H26 Dodecane

十二烷

Dodecyl13 C13H28 Tridecane

十三烷

Tridecyl20 C20H42Icosane

二十烷

Icosyl

21 C21H44Heneicosane

二十一烷

Heneicosyl30 C30H62 Triacontane

三十烷

TriacontylBranched-chainalkanes3-ethyl-3-methylhexane

SomeusefulprefixesforindicatingthenumberofsubstituentgroupsMono-

單取代,一取代Di-

二取代Tri-

三取代Tetra-

四取代Pent(a)-

五取代Hex(a)-

六取代Hept(a)-

七取代Oct(a)-

八取代Nona-

九取代Deca-

十取代2,6-dimethyloctanenot2-ethyl-6-methylheptane3-ethyl-2-methylhexanenot3-isopropylhexaneSomeusefulprefixesusedtonamebranchedalkanes(Commonnames)(normal)n- 正(isomer)iso- 異neo- 新primary 伯，一級(jí)(secondary)sec-仲，二級(jí)(tertiary)tert- 叔，三級(jí)quaternary 季，四級(jí)

n-pentaneneopentaneisobutane正戊烷新戊烷異丁烷

Pentane2,2-dimethylpropane2-methylpropanetert-butanoliso-butanamine

sec-butanamine叔丁醇異丁胺仲丁胺2-methyl-2-propanol2-methylpropanamine1-methylpropanamine

Theunivalentradicalderivedfromacyclicalkeneoralkynehastheendings“-enyl”or“-ynyl”,(alkenealkenyl)(alkynealkynyl),andthepositionofthedoubleortriplebondisindicatedwherenecessary.(unlikealkanealkyl)e.g.

1-propenyl2-butenyl

ethynyl2-propynylThefollowingnon-systematicnamesareretainedEthylene(乙烯）Allene（丙二烯）Acetylene（乙炔）Isoprene（異戊二烯）Vinyl（乙烯基）Allyl（烯丙基）Isopropenyl（異丙烯基）NomenclatureofacyclichydrocarbonswithtwoormoredoubleortriplebondsTwoormoredoublebonds:theendingwillbe“-adiene”,“-atriene”etc.(alkadiene)Twoormoretriplebonds:theendingwillbe“-adiyne”,“-atriyne”etc.(alkadiyne)e.g.

2-methyl-1,3-butadienepropadiene2,5-dimethyl-2,4,6-octatriene

3-ethyl-4-methyl-1,6-heptadiyneNomenclatureofmonocyclicaromatichydrocarbons

苯甲苯二甲苯苯乙烯異丙苯均三甲苯benzenetoluenexylenestyrenecumenemesitylene苯基甲苯基二甲苯基苯乙烯基異丙苯基均三甲苯基芐基PhenyltolylxylylstyrylcumenylmesitylbenzylCommonnamesretainedforthedisubstitutedbenzeneortho-,o- 鄰meta-,m- 間para-,p- 對(duì)

m-methylbenzylm-tolyl3,4-dimethylphenyl3-methylbenzyl

3-tolyl

o-styrylp-cumenyl3,5-dimethyl-4-ethylphenyl

2-styryl4-cumenyl

SomeimportantFamiliesoforganicmoleculesSaturatedhydrocarbons:suchas:Alkanes;cycloalkanes;Un-saturatedhydrocarbons:suchas:alkenes;alkynes;cycloalkenes;cycloalkynes;cycloalkadienes;cycloalkadiynes;Aromaticcompouds:benzene;biphenyl;naphthaleneandotherfusedandpolycyclicaromatichydrocarbons;Compoundswithfunctionalgroups:alkylhalides（鹵代烴）;alcohols（醇）;phenols（酚）;ethers（醚）;amines（胺）;Compoundswithfunctionalgroups:aldehydes（醛）;ketones（酮）;quinones（醌）;carboxylicacids（羧酸）;esters（酯）;acylhalides（酰鹵）;acidanhydrides（酸酐）amides（酰胺）;imides（亞胺）;

Compoundswithfunctionalgroups:

alkylhalides（鹵代烴）;alcohols（醇）;phenols（酚）;ethers（醚）;amines（胺）etc.alkylhalides R-X halogen(-halo)(-Cl,-Br,-F,-I)Alcohols R-OH hydroxygroup(-OH)Phenols Ar-OH hydroxygroup(-OH)Ethers R-O-R’ Alkoxygroup(O-R’)Amines R-NH2 aminogroup(NH2)

Alkylhalides(haloalkaneoralkyl

halide)Alkylhalidesareclassifiedasprimary,secondary,ortertiarydependingonthecarbontowhichthehalogenisattached.

Thecommonnamesofthealkylhalidesareobtainedbycitingthenameofthealkylgroupfollowedbythenameofthehalogen.(alkyl

halide)

IntheIUPACsystem,alkylhalidesarenamedassubstitutedalkanes.Thesubstitutedprefixnamesforthehalogensendin“o”(fluoro,chloro,bromo,iodo).(haloalkane)Alcohols

Thecommonnames,similartoalkylhalides,areobtainedbycitingthenameofthealkylgrouptowhichtheOHgroupisattached,followedbytheword“alcohol”.(alkyl

alcohol)

TheIUPACnameforanalcoholisobtainedbyremovingthe“e”fromthenameofthealkaneandaddingthesuffix“ol”.(alkanol)NomenclatureofalcoholsAminesarecompoundsinwhichoneormorehydrogenofammoniahavebeenreplacedbyalkylgroups.Thereareprimary,secondary,andtertiaryamines.Thisclassificationdependsonhowmanyalkylgroupsarebondedtothenitrogen.

(!!!notcarbon)NomenclatureofaminesThecommonnameofaamineisobtainedbycitingthenamesofthealkylgroupsbondedtothenitrogeninalphabeticalorder.Theentirenameiswrittenasoneword.

(alkylamine)e.g.TherearetwoIUPACapprovedwaytonameanamine.Itcanbenamedasasubstitutedalkaneusingtheprefix“amino”todesignatetheaminesubstituent.(???aminoalkane)Italsocanbeennamedwithafunctionalgroupsuffix----“amine”.The“e”attheendofthealkanenameisreplacedby“amine”.ThenamesofsubstituentsbondedtothenitrogenareprecededbyanN

(initalic)toindicatethatthesubstituentisbondedtoanitrogenratherthantoacarbon.[(N-alkyl)alkanamine]Amineswithfouralkylgroupsbondedtothenitrogen-andthereforeapositivechargeonthenitrogen-arecalledquaternaryammonium

salts.Theirnamesareobtainedbycitingthenamesofthealkylgroupsinalphabeticalorderasaprefixto“ammonium”,followedbythenameofthe

counterion.

[alkylammoniumhalide

(orhydroxideetc)]Nomenclatureofetherssymmetricaletherandasymmetricalether.e.g.Thecommonnameofanetherisobtainedbycitingthenamesofthetwoalkylsubstituents(inalphabeticalorder)followedbytheword“ether”.Thesmallestethersarealmostalwaysnamedbytheircommonnames.(alkylalkyl

ether)

TheIUPACsystemnamesanetherasanalkanethatbearsanalkoxysubstituent.Alkoxysubstituentsarenamedbyremovingthe“yl”fromthenameofthealkylsubstituentandadding“oxy”.(alkoxyalkane)methoxyethoxy1-methylethoxy1,1-dimethylpropoxy

Acarbonylgroup（羰基）

isacarbondoublybondedtoanoxygenandanacylgroup（?；?/p>

isacarbonylgroupattachedtoanalkylsubstituent.Abenzoylgroup（苯甲?；?/p>

isacarbonylgroupattachedtoabenzenering.Thecommonnameofanaldehydeisthesameascarboxylicacid(derivedfromsomeLatinwords).(Latin+aldehyde)TheIUPACnameofanaldehydeisobtainedbyremovingthe“e”fromthealkanenameandadding“-al”.(alkanal)NomenclatureofaldehydesandketonesIfthealdehydegroupisattachedtoaring,thealdehydeisnamedbyadding“carbaldehyde”tothenameofthering.(cycloalkanecarbaldehyde)phenylmethanalCommonname:Onlyafewketonshavecommonnames,suchasacetone(likealdehyde).Commonnamesarealsousedforphenyl-substitutedketones.Theyarecalledphenones.(+one)IUPACname:KetonesarenamedintheIUPACsystembyremovingthe“e”fromthealkanenameandadding“-one”.(alkanone)Derivedname:Likeethers,R-CO-R’canbenamedbycitingthenamesofthetwoalkylsubstituents(inalphabeticalorder)followedbytheword“ketone”.(alkylalkyl

ketone)NomenclatureofketonesCommonnameIUPACnameDerivednameNomenclatureofcarboxylicacidsanditsderivativesX=OH,acarboxylicacidX=halogen,anacylhalideX=OR',anesterX=OCOR',anacidanhydrideX=NRR',anamideNomenclatureofcarboxylicacids

acarboxylgroup

Thefunctionalgroupofacarboxylicacidiscalledacarboxylgroup.Long-chaincarboxylicacidsarecalled“fattyacids”.

Commonname:Carboxylicacids(<6)arefrequentlycalledbytheircommonnames.Theyarenamedbyadding“Latinprefix”before“acid”.?whatisα–carbon?

IUPACname:acarboxylicacidisnamedbyreplaceingthe“e”endingofthealkanenamewith“–oicacid”.(alkanoic

acid)Carboxylicacidsinwhichacarboxylgroupisattachedtoacycliccompoundcanbenamedbyadding“carboxylicacid”tothenameofthecycliccompound.benzoicacidNomenclatureofacylhalidesAcylhalidesarenamedbyusingtheacidnameandreplacingthe“–icacid”with“–ylhalide”(alkanoyl

halide),orbyreplacing“carboxylicacid

”with“carbonylhalide”(cycloalkanecarbonylhalide)benzoylchlorideNomenclatureofacidanhydrides?Doyouknowthemeaningof“anhydride”

R=R’,asymmetricalanhydride

R≠R’,amixedanhydrideSymmetricalanhydridesarenamedbyusingtheacidnameandreplacing“acid”with“anhydride”,mixedanhydridesarenamedbystatingthenameofbothacidgroupsinalphabeticalorderfollowedby“anhydride”.Innaminganester,thenameofthegroupattachedtothe“carboxyloxygen”isstatedfirst.Thisisfollowedbythenameoftheacidwith“-icacid”replacedby“-ate”.Saltsofcarboxylicacidsarenamedinthesameway.

(R’alkyl

R

alkanoate)Nomenclatureofestersethylacetate

AprimaryamideasecondaryamideatertiaryamideAmidesarenamedbyusingtheacidname,replacing“–oicacid”or“-icacid”with“amide”,orbyreplacing“carboxylicacid”with“carboxamide”.(alkanamide)or(cycloalkanecarboxamide)NomenclatureofamidesNomenclatureofnitrilesIncommonnomenclature,nitrilesarenamedbyreplacing“–icacid”with“-onitrile”,ortheyarenamedas“alkyl

cyanide”.(alkyl

cyanide)InIUPACnomenclature,nitrilesarenamedbyadding“-nitrile”tothealkanename.(alkanenitrile)Alkalineearths(堿土)Magnesium(鎂)Calcium(鈣)Aluminum

(鋁)Tin

(錫)Lead

(鉛)TransitionMetals:Titanium(鈦)Chromium(鉻)Manganese(錳)Iron(鐵)Cobalt(鈷)Nickle(鎳)Copper(銅)Zinc(鋅)Silver(銀)Platinum(鉑)Gold(金)Palladium(鈀)

另外必須提供微生物的生長介質(zhì)必須含有諸如硫酸銨、氨水或尿素等含氮化合物，以及無機(jī)磷酸鹽。此外，必需有的恒定的最佳的pH值和溫度。以青霉素G為例，發(fā)酵過程在200小時(shí)后完成，細(xì)胞團(tuán)塊經(jīng)過濾而分離。從濾液中經(jīng)吸收或提取工藝而分離出所需要的活性制劑。細(xì)胞團(tuán)塊，如果并非目的產(chǎn)品，由于其高蛋白質(zhì)含量，可進(jìn)一步用作動(dòng)物飼料。

Additionallythemicroorganismsmustbesuppliedinthegrowthmediumwithnitrogen-containingcompoundssuchasammonium

sulfate,ammonia,orurea,aswellaswithinorganicphosphates.Furthermore,constantoptimalpHandtemperaturearerequired.InthecaseofpenicillinG,thefermentationisfinishedafter200hours,andthecellmassisseparatedbyfiltration.Thedesiredactiveagentsareisolatedfromthefiltratebyabsorptionorextractionprocesses.Thecellmass,ifnotthedesiredproduct,canbefurtherusedasananimalfeedstuffowingtoitshighproteincontent.

利用現(xiàn)代重組技術(shù)，已獲得的微生物可以生產(chǎn)原始基因中并未編碼的多肽。修飾過的大腸桿菌使得產(chǎn)生人類胰島素或前胰島素原類似物的A-和B-鏈成為可能。經(jīng)分離后再選擇性形成二硫鍵，其最終提純由色析（譜）工序來決定。通過這種方式，完全可以不受限制地從任意的動(dòng)物胰腺原料獲得人類胰島素。

Bymodernrecombinanttechniquesmicroorganismshavebeenobtainedwhichalsoallowproductionofpeptideswhichwerenotencodedintheoriginalgenes.ModifiedE.colibacteriamakeitthuspossibletoproduceA-andB-chainsofhumaninsulinorproinsulinanalogs.Thedisulfidebridgesareformedselectivelyafterisolation，andthefinalpurificationiseffectedbychromatographicprocedures.Inthiswayhumaninsulinisobtainedtotallyindependentlyfromanypancreaticmaterialtakenfromanimals.

其他重要的肽，激素和酶，如人類生長激素（HGH），神經(jīng)活性肽，生長抑素，干擾素，組織型纖溶酶原激活劑（TPA），淋巴因子，如鈣調(diào)蛋白的鈣調(diào)節(jié)劑，蛋白疫苗，以及作為診斷用單克隆抗體，也是應(yīng)用這種方法合成的。

Otherimportantpeptides,hormones,andenzymes,suchashumangrowthhormone(HGH),neuroactivepeptides,somatostatin,interferons,tissueplasminogenactivator(TPA),lymphokines,calciumregulatorslikecalmodulin,proteinvaccines,aswellasmonoclonalantibodiesusedasdiagnostics,aresynthesizedinthisway.

一個(gè)單一的微生物中所存在的酶或酶系統(tǒng)，可應(yīng)用于控制的立體定向的和位置定向的化學(xué)反應(yīng)。這個(gè)原理在類固醇化學(xué)尤其有用。在這里，我們只能提及黃體酮經(jīng)微生物法的11-α-位羥基化反應(yīng)制得11-α-羥基黃體酮，一個(gè)用于合成可的松（腎上腺皮質(zhì)酮）的關(guān)鍵產(chǎn)品。今天，分離出的酶很重要，不僅因?yàn)榈矸鄣拿阜ㄌ腔夹g(shù)的重要性以及葡萄糖異構(gòu)化成果糖，而且它們?cè)谟糜谠\斷疾病的無數(shù)檢測程序和用于監(jiān)測治療的酶法分析中也很重要。

Theenzymesorenzymaticsystemswhicharepresentinasinglemicroorganismcanbeusedfordirectedstereospecificandregiospecificchemicalreactions.Thisprincipleisespeciallyusefulinsteroidchemistry.Herewemayreferonlytothemicrobiological11-α-hydroxylationofprogesteroneto11-α-hydroxyprogesterone,akeyproductusedinthesynthesisofcortisone.Isolatedenzymesareimportanttodaynotonlybecauseofthetechnicalimportanceoftheenzymaticsaccharificationofstarch,andtheisomerizationofglucosetofructose,Theyarealsosignificantinthecountlesstestproceduresusedindiagnosingillness,andinenzymaticanalysiswhichisusedinthemonitoringoftherapy.

大量的酶本身可以作為活性成分。因此，含有蛋白酶（如糜蛋白酶，胃蛋白酶和胰蛋白酶），淀粉酶和脂肪酶的制劑產(chǎn)品，大多與合成的抗酸藥相配合，以促進(jìn)消化。鏈激酶和尿激酶是重要的溶血栓劑，而天冬酰胺酶則用作治療白血病中的細(xì)胞生長抑劑。

Anumberofenzymesarethemselvesusedasactiveingredients.Thuspreparationscontainingproteases(e.g.chymotrypsin,pepsin,andtrypsin),amylasesandlipases,

mostlyincombinationwithsyntheticantacids,promotedigestion.Streptokinaseandurokinaseareimportantinthrombolytics,andasparaginaseisusedasacytostaticagentinthetreatmentofleukemia.

最后必須提到的是，酶作為生物催化劑在化學(xué)反應(yīng)的重要應(yīng)用，其中立體專一性和選擇性可以得到應(yīng)用。著名例子有酶裂解N-乙?；?D,L-氨基酸的外消旋體而生成L-氨基酸，從芐基青霉素經(jīng)青霉素酰胺酶作用生產(chǎn)8-氨基青霉烷酸，以及天門冬氨酸酶催化氨對(duì)富馬酸立體專一性加成反應(yīng)以生產(chǎn)L-天門冬氨酸。

在這些應(yīng)用中，酶可以固載的形式—某種方式連接在載體上—使用，也可以雜相催化劑的形式來使用。這是有利的，因?yàn)樗鼈兛梢院苋菀讖姆磻?yīng)介質(zhì)中分離，并回收再利用。

Finallymentionmustbemadeoftheimportantuseofenzymesas‘biocatalysts’inchemicalreactionswheretheirstereospecificityandselectivitycanbeused.KnownexamplesaretheenzymaticcleavageofracematesofN-acetyl-D,L-aminoacidstogiveL-aminoacids,

theproductionof8-aminopenicillanicacidfrombenzylpenicillinbymeansofpenicillinamidaseandtheaspartase-catalysedstereospecificadditionofammoniatofumaricacidinordertoproduceL-asparticacid.Intheseapplicationstheenzymescanbeusedinimmobilizedforms-somehowboundtocarriers-andsousedasheterogeneouscatalysts.Thisisadvantageousbecausetheycantheneasilybeseparatedfromthereactionmediumandrecycledforfurtheruse.benzylpenicillinAminopenicillanicacidpenicillinamidaseFumaricacidaspartaseL-asparticacid

另一個(gè)基于蛋白酶專一性作用的重要工藝是應(yīng)用于半合成人胰島素的生產(chǎn)。這從豬胰島素開始，其中在B鏈的30-位的丙氨酸由于胰蛋白酶選擇性作用被替換為蘇氨酸叔丁基酯。分離(生成的)胰島素酯，水解為人胰島素，最后經(jīng)色析（譜）法程序而純化。

酶的來源不僅包括微生物，也包括植物的和動(dòng)物的材料。

Anotherimportantprocessdependingonthespecificactionofproteasesisappliedfortheproductionofsemisynthetichumaninsulin.Thisstartswithpiginsulininwhichthealanineinthe30-positionoftheB-chainisreplacedbyathreoninetert-butylesterbytheselectiveactionoftrypsin.Theinsulinesterisseparated,hydrolyzedtohumaninsulinandfinallypurifiedbychromatographicprocedures.Sourcesforenzymesincludenotonlymicroorganismsbutalsovegetableandanimalmaterials