有機化學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（谷丙轉氨酶，谷氨酸轉氨酶、丙氨酸氨基轉移酶，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）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是體內催化α-酮酸氧化脫羧的輔酶，也是磷酸戊糖途徑中轉酮酶的輔酶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．結構與芳香性呋喃、噻吩、吡咯，在結構上都符合Hückel的關于芳香性的規(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)分子的結構特點：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，取代主要發(fā)生在α

位發(fā)生親電取代反應的反應活性：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此反應可用于從有機物中除去噻吩，或是用于提純噻吩。60(4)Friedel-Craftsacylation（傅-克?；磻?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,質子泵抑制劑77BenzylpenicillinSodium(potassium)(K)78Albendazole,阿苯達唑,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