有機(jī)化學(xué)Chap.14 heterocyclic compounds and vitamins課件

1Chapter14HeterocyclicCompoundsandVitaminsHeteroatoms(雜原子):O,S,N雜環(huán)是與與碳環(huán)相對的概念，指的是構(gòu)成環(huán)的原子含有氮、氧或硫等原子。（雜環(huán)化合物）雜環(huán)可以是芳環(huán)（如吡啶），也可以是脂環(huán)（如四氫呋喃）2cyclicanhydridelactideThesecompoundshavecollectivefeature,theyareinstable,theringsbeopenedeasily.epoxidelactonelactam環(huán)上含雜原子的非雜環(huán)化合物3Section1.ClassificationanNomenclatureⅠ.Classificationmonoringheterocycliccondensedringheterocyclicpentabasichexabasic稠雜環(huán)雜環(huán)5若環(huán)上有取代基，以雜環(huán)為母體，將環(huán)進(jìn)行編號，雜原子為“1”。也可用（雜原子的鄰位碳原子）、、來表示環(huán)上取代基的位置。若環(huán)上有二個或二個以上相同的雜原子，則應(yīng)使雜原子的位次和保持最小若連有二個或二個以上不同的雜原子，則按OSNHN的順序編號6furan呋喃thiophene噻吩pyrrole吡咯thiazole噻唑imidazole咪唑pyrazole吡唑oxazole噁唑11112345312451234512345Five-memberedrings4-Methylimidazole，4-甲基咪唑134Consumergroupfindscancer-causingchemicalincolasMarch05,2012，LosAngelesTimes10pyrimidine，嘧啶123456pyridine,py,吡啶114dioxane二噁烷，二氧六環(huán)Six-memberedrings4H-pyran，吡喃12成龍代言霸王洗發(fā)水含二噁烷14quinoline喹啉isoquinoline異喹啉12345671234567812345678123495678indole吲哚purine嘌呤condensedheterocycles155-methylimidazole-furfuraldehyde糠醛3-methylindole8-hydroxylquinolineSkatole,糞臭素16Section2Six-MemberedHeterocyclesⅠ.Pyridine(吡啶)1.Basicity··17sixelectronsaredelocalized(離域)intheringAporbitalonNoverlapswithadjacentporbitals,makingtheringcompletelyconjugated18Thesequenceofbasicity:Why？P.18914-120苯胺(aniline)········p-conjugation,delocalized(離域)21pKa4.65.29.2511.0pKa越大，酸性越小，其共軛堿的堿性越大Thensequenceofbasicity:23Thesubstitutionreactionsofpyridinesimilartothereactionsofnitrobenzene,substitutionatthemeta,or3-position.243.OxidationandReduction26pKa5.211.011.010.8pKa越大，酸性越小，其共軛堿的堿性越大piperidine（哌啶）的堿性相當(dāng)于脂肪族仲胺27ImportantDerivativesofPyridinepyridoxine吡哆醇pyridoxal吡哆醛pyridoxamine吡哆胺Pyridoxine,pyridoxalandpyridoxaminecomposeVitaminB6.（水溶性）28Pyridoxalphosphate磷酸吡哆醛，PLPPyridoxaminephosphate磷酸吡哆胺，PMP30Enzyme:pyridoxalcoenzymecomplexEnzyme:pyridoxaminecoenzymecomplexAlanine丙氨酸pyruvicacid丙酮酸L-glutamicacidL-谷氨酸-ketoglutaricacid-酮戊二酸Alanineaminotransferase（谷丙轉(zhuǎn)氨酶，谷氨酸轉(zhuǎn)氨酶、丙氨酸氨基轉(zhuǎn)移酶，簡稱GPT、ALT）Nicotinicacid煙酸,尼克酸NicotineLethaldose:60mg(directinjection)Recently,somereportssaid,nicotinecancureseniledementia（阿爾茨海默病，Alzheimerdisease，AD）ContentofNicotine:20~30mg/acigarette120mg/acigar32Nicotinicacid,vitaminB3

煙酸,尼克酸,維生素B3Nicotinamide,煙酰胺

維生素B3的另一種形式vitaminPP,pellagra-preventivefactor抗糙皮病因子，抗癩皮病因子33NAD+

、NADH和NADP+

、NADPH（P.255）NAD+Nicotinamideadeninedinucleotide，煙酰胺腺嘌呤二核苷酸（輔酶Ⅰ）NADHoxidizedform（氧化型）reducedform（還原型）+H+34reducedformoxidizedformNADH+H+NAD+Alcoholdehydrogenases

(ADH)，醇脫氫酶35NADP+Nicotinamideadeninedinucleotidephosphate煙酰胺腺嘌呤二核苷酸磷酸酯（輔酶Ⅱ）NADPHoxidizedform（氧化型）reducedform（還原型）+H+36isocitrateacid異檸檬酸isocitratedehydrogenase異檸檬酸脫氫酶-ketoglutaricacid-酮戊二酸異檸檬酸有兩種類型的酶：一種以NAD+為輔酶的酶，另一種以NADP+為輔酶的。在三羧酸循環(huán)中正常起作用的是以NAD+為輔酶的酶37Epibatidine,地棘蛙素對小鼠的鎮(zhèn)痛活性為嗎啡的200—500倍,且不被阿片受體的拮抗劑納絡(luò)酮所阻斷。三色地棘蛙Epipedobatestricolor38Ⅱ.Pyrimidine(嘧啶)uracil,U尿嘧啶cytosine,C胞嘧啶thymine,T胸腺嘧啶39Keto–enoltautomerism（酮-烯醇互變異構(gòu)）40Fluorouracil,5-FU,5-氟尿嘧啶5-FUisatypicalantineoplasticagent41trimethyoprim(TMP),三甲氧芐氨嘧啶Chemitrim(百炎凈):400mgSMZ+80mgTMPsulfamethoxazole(SMZ),orSinomin,磺胺甲(異)噁唑,新諾明42VitaminB1,Thiamine,硫胺素（水溶性）抗神經(jīng)炎素、抗腳氣病因子43SB44Thiaminepyrophosphate，硫胺素焦磷酸（酯），TPP（P.258）硫胺素焦磷酸TPP是體內(nèi)催化α-酮酸氧化脫羧的輔酶，也是磷酸戊糖途徑中轉(zhuǎn)酮酶的輔酶45dissociableproton46VitaminB2,riboflavin，核黃素（水溶性）核糖醇（Ribitol）蝶啶（pteridine）47Folicacid,VitaminB9,葉酸（水溶性）蝶啶（pteridine）對氨基苯甲酸（p-aminobenzoicacid，PABA）谷氨酸（glutamicacid，Glu）48Folicacidtetrahydrofolicacid四氫葉酸，輔酶F[H]E,VB1249一、含一個雜原子的芳香五元雜環(huán)1．結(jié)構(gòu)與芳香性呋喃、噻吩、吡咯，在結(jié)構(gòu)上都符合Hückel的關(guān)于芳香性的規(guī)則。Section3Five-MemberedHeterocyclesHückel’srule:Allplanar,cyclic,fullyconjugatedmoleculeswith4n+2(n=0,1,2,3…)electronswillbearomatic(especiallystable).50pyrrole吡咯51furan呋喃52Sthiophene噻吩Sorbitalstructureofthiophene53五元雜環(huán)分子的結(jié)構(gòu)特點(diǎn)：鍵長有一定的平均化，但不像苯那樣完全平均化。芳香性較苯環(huán)差，有某種程度的不飽和化合物的性質(zhì)和環(huán)的不穩(wěn)定性環(huán)上電子云密度比苯環(huán)上的高，因此比苯更容易發(fā)生親電取代反應(yīng)，取代主要發(fā)生在α

位發(fā)生親電取代反應(yīng)的反應(yīng)活性：54ChemicalProperties:1.Hydrogenationtetrahydrofuran,THF四氫呋喃55tetrahydropyrroleorpyrrolidine四氫吡咯，吡咯烷562.Substitution(1)Halogenation57(2)Nitration58(3)SulfonylationP.19259此反應(yīng)可用于從有機(jī)物中除去噻吩，或是用于提純噻吩。60(4)Friedel-Craftsacylation（傅-克?；磻?yīng)）,BF3613.AcidandBaseProperties······62Basicity:pKa11.211.04.60.0pKa越大，酸性越小，其共軛堿的堿性越大>>pyrrolidine（四氫吡咯，吡咯烷）的堿性相當(dāng)于脂肪族仲胺63卟啉(Porphyrin)R=H,卟吩(Porphine)Someimportantderivativesoffive-memberedheterocycles64葉綠素(chlorophyllsa)血紅素B(血基質(zhì)B，hemeB)6566維生素B12(VitamineB12,VB12)，鈷胺素，氰鈷胺(脫氧腺苷基)67二、含兩個雜原子的芳香五元雜環(huán)thiazole噻唑imidazole咪唑oxazole噁唑68(delocalized離域)69≡70orbitalstructureofoxazole(噁唑)71Sorbitalstructureofthiazole(噻唑)72咪唑化合物的互變異構(gòu)23451234514-甲基咪唑5-甲基咪唑73組胺（histamine)←N3N2→←N1N1、N2、N3堿性大小次序：N3>N2>N174Cimetidine,西咪替丁,甲腈咪胍,泰胃美HistamineH2-receptorantagonistthatinhibitsstomachacidproduction，usedinthetreatmentofheartburn（胃灼熱）andpepticulcers（消化性潰瘍）.75Ranitidine,雷尼替丁Famotidine,法莫替丁76Omeprazole,奧美拉唑,Losec,洛賽克AstraZeneca,阿斯利康Protonpumpinhibitor,質(zhì)子泵抑制劑77BenzylpenicillinSodium(potassium)(K)78Albendazole,阿苯達(dá)唑,腸蟲清79Section4condensedheterocyclesPurine（嘌呤）

9H-purine

7H-purine9H-purinecantautomerizetoform7H-purine.Mostnaturalproductsarethederivativesof9H-purine.Incontrast,mostsyntheticalproductsarethederivativesof7H-purine.80adenine,A,腺嘌呤guanine,G,鳥嘌呤T