有机化学Chap.14 heterocyclic compounds and vitamins课件

1Chapter14HeterocyclicCompoundsandVitaminsHeteroatoms(杂原子):O,S,N杂环是与与碳环相对的概念，指的是构成环的原子含有氮、氧或硫等原子。（杂环化合物）杂环可以是芳环（如吡啶），也可以是脂环（如四氢呋喃）2cyclicanhydridelactideThesecompoundshavecollectivefeature,theyareinstable,theringsbeopenedeasily.epoxidelactonelactam环上含杂原子的非杂环化合物3Section1.ClassificationanNomenclatureⅠ.Classificationmonoringheterocycliccondensedringheterocyclicpentabasichexabasic稠杂环杂环5若环上有取代基，以杂环为母体，将环进行编号，杂原子为“1”。也可用（杂原子的邻位碳原子）、、来表示环上取代基的位置。若环上有二个或二个以上相同的杂原子，则应使杂原子的位次和保持最小若连有二个或二个以上不同的杂原子，则按OSNHN的顺序编号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，二氧六环Six-memberedrings4H-pyran，吡喃12成龙代言霸王洗发水含二噁烷14quinoline喹啉isoquinoline异喹啉12345671234567812345678123495678indole吲哚purine嘌呤condensedheterocycles155-methylimidazole-furfuraldehyde糠醛3-methylindole8-hydroxylquinolineSkatole,粪臭素16Section2Six-MemberedHeterocyclesⅠ.Pyridine(吡啶)1.Basicity··17sixelectronsaredelocalized(离域)intheringAporbitalonNoverlapswithadjacentporbitals,makingtheringcompletelyconjugated18Thesequenceofbasicity:Why？P.18914-120苯胺(aniline)········p-conjugation,delocalized(离域)21pKa4.65.29.2511.0pKa越大，酸性越小，其共轭碱的碱性越大Thensequenceofbasicity:23Thesubstitutionreactionsofpyridinesimilartothereactionsofnitrobenzene,substitutionatthemeta,or3-position.243.OxidationandReduction26pKa5.211.011.010.8pKa越大，酸性越小，其共轭碱的碱性越大piperidine（哌啶）的碱性相当于脂肪族仲胺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（谷丙转氨酶，谷氨酸转氨酶、丙氨酸氨基转移酶，简称GPT、ALT）Nicotinicacid烟酸,尼克酸NicotineLethaldose:60mg(directinjection)Recently,somereportssaid,nicotinecancureseniledementia（阿尔茨海默病，Alzheimerdisease，AD）ContentofNicotine:20~30mg/acigarette120mg/acigar32Nicotinicacid,vitaminB3

烟酸,尼克酸,维生素B3Nicotinamide,烟酰胺

维生素B3的另一种形式vitaminPP,pellagra-preventivefactor抗糙皮病因子，抗癞皮病因子33NAD+

、NADH和NADP+

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

(ADH)，醇脱氢酶35NADP+Nicotinamideadeninedinucleotidephosphate烟酰胺腺嘌呤二核苷酸磷酸酯（辅酶Ⅱ）NADPHoxidizedform（氧化型）reducedform（还原型）+H+36isocitrateacid异柠檬酸isocitratedehydrogenase异柠檬酸脱氢酶-ketoglutaricacid-酮戊二酸异柠檬酸有两种类型的酶：一种以NAD+为辅酶的酶，另一种以NADP+为辅酶的。在三羧酸循环中正常起作用的是以NAD+为辅酶的酶37Epibatidine,地棘蛙素对小鼠的镇痛活性为吗啡的200—500倍,且不被阿片受体的拮抗剂纳络酮所阻断。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-烯醇互变异构）40Fluorouracil,5-FU,5-氟尿嘧啶5-FUisatypicalantineoplasticagent41trimethyoprim(TMP),三甲氧苄氨嘧啶Chemitrim(百炎净):400mgSMZ+80mgTMPsulfamethoxazole(SMZ),orSinomin,磺胺甲(异)噁唑,新诺明42VitaminB1,Thiamine,硫胺素（水溶性）抗神经炎素、抗脚气病因子43SB44Thiaminepyrophosphate，硫胺素焦磷酸（酯），TPP（P.258）硫胺素焦磷酸TPP是体内催化α-酮酸氧化脱羧的辅酶，也是磷酸戊糖途径中转酮酶的辅酶45dissociableproton46VitaminB2,riboflavin，核黄素（水溶性）核糖醇（Ribitol）蝶啶（pteridine）47Folicacid,VitaminB9,叶酸（水溶性）蝶啶（pteridine）对氨基苯甲酸（p-aminobenzoicacid，PABA）谷氨酸（glutamicacid，Glu）48Folicacidtetrahydrofolicacid四氢叶酸，辅酶F[H]E,VB1249一、含一个杂原子的芳香五元杂环1．结构与芳香性呋喃、噻吩、吡咯，在结构上都符合Hückel的关于芳香性的规则。Section3Five-MemberedHeterocyclesHückel’srule:Allplanar,cyclic,fullyconjugatedmoleculeswith4n+2(n=0,1,2,3…)electronswillbearomatic(especiallystable).50pyrrole吡咯51furan呋喃52Sthiophene噻吩Sorbitalstructureofthiophene53五元杂环分子的结构特点：键长有一定的平均化，但不像苯那样完全平均化。芳香性较苯环差，有某种程度的不饱和化合物的性质和环的不稳定性环上电子云密度比苯环上的高，因此比苯更容易发生亲电取代反应，取代主要发生在α

位发生亲电取代反应的反应活性：54ChemicalProperties:1.Hydrogenationtetrahydrofuran,THF四氢呋喃55tetrahydropyrroleorpyrrolidine四氢吡咯，吡咯烷562.Substitution(1)Halogenation57(2)Nitration58(3)SulfonylationP.19259此反应可用于从有机物中除去噻吩，或是用于提纯噻吩。60(4)Friedel-Craftsacylation（傅-克酰化反应）,BF3613.AcidandBaseProperties······62Basicity:pKa11.211.04.60.0pKa越大，酸性越小，其共轭碱的碱性越大>>pyrrolidine（四氢吡咯，吡咯烷）的碱性相当于脂肪族仲胺63卟啉(Porphyrin)R=H,卟吩(Porphine)Someimportantderivativesoffive-memberedheterocycles64叶绿素(chlorophyllsa)血红素B(血基质B，hemeB)6566维生素B12(VitamineB12,VB12)，钴胺素，氰钴胺(脱氧腺苷基)67二、含两个杂原子的芳香五元杂环thiazole噻唑imidazole咪唑oxazole噁唑68(delocalized离域)69≡70orbitalstructureofoxazole(噁唑)71Sorbitalstructureofthiazole(噻唑)72咪唑化合物的互变异构23451234514-甲基咪唑5-甲基咪唑73组胺（histamine)←N3N2→←N1N1、N2、N3碱性大小次序：N3>N2>N174Cimetidine,西咪替丁,甲腈咪胍,泰胃美HistamineH2-receptorantagonistthatinhibitsstomachacidproduction，usedinthetreatmentofheartburn（胃灼热）andpepticulcers（消化性溃疡）.75Ranitidine,雷尼替丁Famotidine,法莫替丁76Omeprazole,奥美拉唑,Losec,洛赛克AstraZeneca,阿斯利康Protonpumpinhibitor,质子泵抑制剂77BenzylpenicillinSodium(potassium)(K)78Albendazole,阿苯达唑,肠虫清79Section4condensedheterocyclesPurine（嘌呤）

9H-purine

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