北京大学有机化学课件第十五章糖类化合物

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1、Chapter 15 Saccharides 糖类化合物糖类化合物Saccharides(or Carbohydrates):糖类糖类;碳水化合物碳水化合物衣，食，住，行衣，食，住，行 息息相关息息相关Starch(淀粉）：polysaccharides能量 来源Paper:cellulose(纤维素）纤维素）Sucrose(蔗糖）:disaccharides植物的光合作用：CO2 +H2OSaccharideCarbohydrate?Glucose(C H2O)6Cn(H2O)mSaccharides 结构与保护作用：纤维素、几丁质、果胶结构与保护作用：纤维素、几丁质、果胶 能量来源：葡萄糖

2、、淀粉、糖原，能量来源：葡萄糖、淀粉、糖原，ATP复杂的生物学功能复杂的生物学功能重要的生命物质重要的生命物质 影响蛋白质的折叠、溶解、半衰期、抗原性、生物活性；影响蛋白质的折叠、溶解、半衰期、抗原性、生物活性；信息分子参与生命活动中的各种识别和信号转导；信息分子参与生命活动中的各种识别和信号转导；Carbohydrate chemistry/Chemical glycobiologyGlycobiologyGeomics、Proteomics、Glycomics 糖类药物糖类药物(Carbohydrate Drugs)Saccharides血型物质与血型决定簇血型物质与血型决定簇A型型:Y=

3、NHAcB型型:Y=OHAB性性:Y=NHAc or Y=OH O型型ProteinOOOOOOHOHHOYOHOHOHHOOHH3CONHAcHOOHOXProteinOOOOHOHOHHOOHH3CONHAcHOOHOXHO血型血型？SaccharidesOOSO3-HOHO-O3SHNOOHO2CHOOHOOOSO3-O3SHN-O3SOOOHOCO2HOSO3-OOHOOSO3-O3SHNOMe肝素五糖(Heparin Pentasaccharide)OHHOHOOHHNOH3CHOOHOOOHHOOHOOOHHOOHOH阿卡波糖(Acarbose)OOOOOOSO2NH2 托吡酯(T

4、opiremate)糖类药物糖类药物(Carbohydrate Drugs)SaccharidesOR1R1NH2NH2OH2NHONHR2OOOHHOH2NOH卡那霉素(Kanamycin)R1=OH,R2=H敌拜卡霉素(Dibekacin)R1=H,R2=H阿拜卡霉素(Arbelkacin)R1=H,R2=COCH(OH)CH2CH2NH2OHOHOOHAcHNCO2HHNNH2NHRelenzaOOHHOHOOOMeHOHOOHOOHOOHAcHNOOHOOHOHOOHOOHHOOCeramideGlobo H 抗原OCO2HOHOAcHNHOHOOHHOOHOOHAcHNOOOHOHO

5、OHOOHHOOCeramideGanglioside GM2糖类药物糖类药物(Carbohydrate Drugs)Saccharides一、一、Definitions:1.Carbohydrates:多羟基的醛，多羟基的酮多羟基的醛，多羟基的酮2.Monosaccharides:最小的糖分子最小的糖分子,不能水解不能水解3.Disaccharides:水解成水解成两个两个单糖分子单糖分子5.Polysaccharides:水解成水解成多个多个单糖分子单糖分子(9)4.Oligosaccharides水解成水解成多个多个单糖分子单糖分子(2 9)二、二、Classification:根据根据

6、功能基功能基Aldose(醛糖醛糖):Ketose(酮糖酮糖):SaccharidesCH2OHCCHHOCOHHCOHHCH2OHOCHOCCHHOCOHHCOHHCH2OHHOHGlucoseFructose根据根据C数数丙糖丙糖(triose)丁糖丁糖(tetrose)戊糖戊糖(pentose)D-ribose己糖己糖(hexose)GlucoseFrucose根据氧化根据氧化反应性质反应性质Reducing sugarNon-reducing sugar蔗糖蔗糖SaccharidesSaccharides三、三、Structure of Monosaccharides:1.开链结构及构

7、型开链结构及构型(Chain Structures and Configurations)：具有多个手性中心，2n分子有旋光分子有旋光甘油醛：甘油醛：CHOCH2OHHOHCHOCH2OHHHOD-(+)-GlyceraldehydeL-(-)-Glyceraldehyde*CHOCOHHCH2OHCHOCCHHOCOHHCOHHCH2OHHOH*CH2OHCCHHOCOHHCOHHCH2OHO*GlucoseFructoseSaccharides开链结构式的表示开链结构式的表示Fischer 投影式投影式上下（氧化态）（氧化态）高低CHOOHHHHOOHHCH2OHOHHCHOHOHHOHH

8、OHCH2OHHOH213456一对对映体一对对映体D-GlucoseL-GlucoseSaccharides非对映异构体非对映异构体Epimer 差向异构体差向异构体CHOOHHHHOOHHCH2OHOHH213456CHOOHHHHOHHOCH2OHOHH213456D-GlucoseD-MannoseCHOOHHHHOOHHCH2OHOHH213456CHOOHHOHHOHHCH2OHOHH213456D-GlucoseD-AlloseCHOOHHHHOOHHCH2OHOHH213456CHOHHOHHOOHHCH2OHOHH213456D-GlucoseD-Galactose甘油醛：C

9、HOCH2OHHOHCHOCH2OHHHOD-(+)-GlyceraldehydeL-(-)-GlyceraldehydeSaccharides糖构型表示法：糖构型表示法：D/L-Fischer 投影式；与甘油醛比较CHOOHHHHOOHHCH2OHOHHCHOHOHHOHHOHCH2OHHOH213456D-GlucoseL-GlucoseCHOOHHOOHCH2OHOHCHOCH2OH简化式简化式SaccharidesHOHCHOCH2OHCH2OHOHHOHHCHOCH2OHHOHHOHCHOCH2OHOHHOHHHOHCHOCH2OHOHHOHHHOHCHOCH2OHOHHHHOHOH

10、CHOCH2OHHOHOHHOHHHOHCHOCH2OHHOHOHHOHHHOHCHOCH2OHHOHOHHHHOHOHCHOCH2OHHOHOHHHHOHOHCHOCH2OHHOHHHOOHHHOHCHOCH2OHHOHHHOOHHHOHCHOCH2OHHOHHHOHHOHOHCHOCH2OHHOHHHOHHOHOHCHOCH2OHOHHHHOHOHCHOD-GlyceraldehydeD-Erythrose(D-赤藓糖)D-Threose(D-苏糖)D-Ribose(D-核糖)D-Arabinose(D-阿拉伯糖)D-Xylose(D-木糖)D-Lyxose(D-来苏糖)D-Allose(

11、D-阿洛糖)D-Altrose(D-阿卓糖)D-Glucose(D-葡萄糖)D-Mannose(D-甘露糖)D-Gulose(D-古罗糖)D-Idose(D-艾杜糖)D-Galactose(D-半乳糖)D-Talose(D-塔洛糖)D-醛糖系列醛糖系列D-，L-型糖互为一对型糖互为一对对映体对映体自然界存在的糖大多数都是自然界存在的糖大多数都是D-型型D.L.只用在糖、只用在糖、-氨基酸、氨基酸、-羟基酸的构型表示羟基酸的构型表示SaccharidesSaccharides(1)Glucose +Tollens Glucose +Fehling Glucose +NaHSO3acetal实验现

12、象实验现象RCHO+2CH3OHRCHOCH3OCH3dry HClC6H12O6+CH3OHdry HCl(C6H11O5)OCH3(2)(3)Mutarotation(变旋现象）变旋现象）+112 Glucose 溶液+52.7放置放置Saccharides+18.7 Glucose 溶液(4)IR,C=O;1H NMR,COH异常现象异常现象？糖中的糖中的-CHO不是游离不是游离的，而是以的，而是以半缩醛半缩醛的形式存在。的形式存在。SaccharidesOHOHOOHOHOHOHOHOOHOHOHO-D-吡喃葡萄糖-D-吡喃葡萄糖123456123456OOHHOHOOHOHOOHOH

13、OHHOHO-D-呋喃果糖-D-呋喃果糖O123456123456Haworth 透视式透视式糖环的编号糖环的编号-、-异构体的定义异构体的定义端基异构体端基异构体(anomer)非对映异构体非对映异构体差向异构体差向异构体2.Cyclic Structures and Conformations:Saccharides如何解释如何解释Mutarotation(变旋现象）变旋现象）？CHOCH2OH开链 D-GlucoseOHOHOOHOHOH-D-吡喃葡萄糖OHOHOOHOHOH-D-吡喃葡萄糖C4-C5OHCHOOHHOOHHHHHHOCH2Fischer向右横倒，弯曲CHOCH2OHOH

14、HHOHOHHOHHD-GlucoseFischer123456OHOHOOHOHOHOHOHOOHOHOH-OHOHOHOHCH2OHOH123564Saccharides-D-(+)-Glu +112m.p.146C开链D-(+)-Glu-D-(+)-Glu +18.7m.p.150C36.4%0.5%63.6%(+112)36.4%+(+18.7)63.6%=52.7OHOHOOHOHOHOHOHOOHOHOHCHOCH2OHOHHHOHOHHOHH如何实现如何实现Fischer投影式投影式Haworth透视式透视式？Fischer,左侧基团Haworth，环上；右侧基团环下Saccha

15、ridesOHOHOOHOHOHOHOHOOHOHOH-D-吡喃葡萄糖-D-吡喃葡萄糖CHOCH2OHOHHHOHOHHOHHD-GlucoseC4-C5FischerOHCHOOHHOOHHHHHHOCH2OHOHOHOHCH2OHOH12356向右横倒，弯曲Fischer1234564CHOCH2OHOHHOOHOHD-GlucoseOHOHOHOHCH2OHOH12356OHOOHOHCH2OHOHHemiacetal123456CH3OH/H+OHOOHOHCH2OHOCH3123456-or -甲基葡萄糖苷-,-isomersEpimers(端基差向异构体）互为非对映异构体Sacch

16、arides环状缩醛的形成：环状缩醛的形成：Saccharides吡喃己醛糖吡喃己醛糖吡喃戊醛糖吡喃戊醛糖&吡喃己酮糖吡喃己酮糖OHOHOOHOHOH2134521345D-OHOOHOHOHOHL-Haworth式中构型的判断式中构型的判断OOH2134521345L-OOHCH2OHD-呋喃己醛糖呋喃己醛糖CHOHHOHHOOHHCH2OHOHHCHOOHCHHHHOOHHCH2OHOH*OOHOHOH*R-D-呋喃半乳糖端基异构体的确定端基异构体的确定C5-CH2OHC4-OH/C5-OHC5-构型(R-,S-)SaccharidesOOHHOHOOHOHN式(I,4C1式），较稳定优势

17、构象A式(II,1C4式），不稳定OOHOHHOHOOH-D-GlucoseOOHHOHOOHOH-D-GlucoseConformationsOHOHOOHOHOHOHOHOOHOHOHCHOCH2OHOHHHOHOHHOHH-,36.4%-,63.6%Anomeric EffectOOR-OOR-形成糖苷？SaccharidesC2C6羟基取代时羟基取代时：(端基效应端基效应)溶剂的作用：极性溶剂非极性溶剂CCH2OHOHOHHOOHOHD-Glucose.OHHOOHCCH2OHOHHO-D-(+)-GlucoseOCH2OHHOOHOHOHorOOHHOHOOHOHorOHHOOHCC

18、H2OHHOHO-D-(+)-GlucoseorOCH2OHHOOHOHOHOOHHOHOOHOHorSaccharidesSaccharidesCH2OHHOHOHHHHOHOHCHOOCH2OHHOOHOHOHOOHHOHOOHOHCH2OHHOHHHOHHOHOHCHOOCH2OHHOOHOHOHOOHHOHOOHOHCH2OHHOHOHHHHOHOHCHOOCH2OHHOOHHOOHOOHHOHOOHOHD-GlucoseD-GalactoseD-MannoseSaccharidesCH2OHOHHOHHHOHCHOOHOOHOHOHCH2OHOHHOHHHHCHOOHOOHOHCH2

19、OHHOHOHHHHOOCH2OHOHOOHHOOHOHOHOOHHOOHOHD-FructoseD-Ribose2-Deoxy-D-ribose3、Chemical Reaction:-CHO:Nucleophilic Addition Oxidation,Reduction-OH:酯化酯化，醚化，醚化，脱水脱水复合性质（各基团相互影响）复合性质（各基团相互影响）-特性特性CHOCH2OHOHHOOHOHD-GlucoseSaccharides.Formation of glycosides 糖的成苷反应糖的成苷反应 糖的环状半缩醛或半缩酮形式糖的环状半缩醛或半缩酮形式Acetal or K

20、etal 成苷反应，糖苷成苷反应，糖苷 Glycosides OOHHOHOOHOHCH3OHDry HClD-GlucoseOOHHOHOOHOMeOOHHOHOOHOMe+Methyl-D-glucoside Methyl-D-glucoside SaccharidesOORROROORX+Glycosyl donorHYCatalystSolventTemperatureOORROROORYHY=HOR,HSR,HNRR,HCAcceptorYieldSelectivityAvailabilitySaccharides糖苷的性质糖苷的性质稳定，无变旋现象稳定，无变旋现象碱性条件稳定碱性条

21、件稳定稀酸或酶的作用稀酸或酶的作用NHOHOHOOHOHOOHOHOOHOHSCNCH2CHCH2OSO3K硫苷硫苷(芥子苷芥子苷)OOHHONNHOOH3CHNNHOOOOHHOOH氧苷氧苷(尿兰母尿兰母)氮苷氮苷(脱氧胸苷脱氧胸苷)碳苷碳苷(伪尿嘧啶核苷)OOHHOHOOHXRglycosidic bondglycosyl partaglycon,geninOHOHOOHOHOOHOCH2HOOHOHOOHOHOOHOHOCHCN水杨苷，水杨苷，解热镇痛解热镇痛OHOHOOHOHOCH2OH熊果苷熊果苷尿道消毒尿道消毒皮肤增白剂皮肤增白剂苦杏仁苷苦杏仁苷毒性毒性SaccharidesPro

22、teinOOOOHOHOHHOOHH3CONHAcHOOHOXHO.Esterification(酯化反应）：酯化反应）：OHOOH OHOHOHOOH OHOPOHOHOPOOHOHHO+核糖核酸D-核糖SaccharidesOAOHOHOPOOO-PO-OPO-OOOATPOAOHOHOPOOO-PO-OOADP-D-五乙酰葡萄糖OHOHOOHOHOH+(CH3CO)2OH3CCClOOAcOAcOOAcOAcOAcSaccharides条件：弱碱KOAc,Pyridine保护基CHOCH2OPOHOHOOHHOOHOH6-磷酸-D-GlucoseCH2HOOHOPOHOHO磷酸甘油酯.醚

23、化反应醚化反应SaccharidesOHOOHOHOHOHCH3IAg2OOH3COH3COOCH3OCH3OCH385%Williamson 醚合成法醚合成法OOHHOHOOHOMeMethyl -D-glucopyranoside OOHHOHOOHOHCH3OHdry HClOOHHOHOOHOMe+Me2SO4NaOH稀HClOOMeMeOMeOOMeOHOOMeMeOMeOOMeOMeOOHHOHOOHOMeSaccharides.环缩醛、酮的生成环缩醛、酮的生成1,2-diol or 1,3-diolCis-OOHOHHOOHOH+CH3CCH3O2OOHOOOOH3CH3CH3C

24、CH3H2SO4OOHHOHOOHOCH3+PhCHOOOOHOOHOCH3PhH+糖化学中羟基的保护糖化学中羟基的保护SaccharidesCH2OHCHOHOHOOHHOD-GlucoseH2/NiCH2OHCH2OHHOHOOHHOO黑醋酸菌CH2OHCH2OHHOOHHOOL-SorboseOOHOHOHHOHOAcetone/H2SO4OOOHOOONaOCl/NaOHHClOOHOHOHHOHOOOOHOHOHHOHOOHOOHOHOHOVitamin C(Ascorbic Acid).Dehydration(脱水脱水):CHOCH2OHOHOHOHH+OCHOHOHOOCHOD-

25、核糖-呋喃甲醛（糠醛）CHOCH2OHOHOHOHOHH+OCHOHOHOCH2OHOCHOCH2OHD-阿洛糖5-羟甲基-呋喃甲醛Saccharides.Epimerism 差向异构化差向异构化糖与碱的作用糖与碱的作用CHOCH2OHOHHHOOHOHD-GlucoseB*CHOHCOHCH2OHOHOHHO烯醇式CHOCH2OHOHHOOHOHD-Glucosea*CHOCH2OHHOHOOHOHD-Mannoseb*CH2OHCH2OHHOOHOHOD-FructosecSaccharidesD-Glucose碱水溶液碱水溶液D-glucose+D-Mannose+D-Fructose.

26、Formation of Osazone Epimers 糖脎的形成糖脎的形成/差向异构体差向异构体CHOCHOH+NHNH2A.CHCHOHNNHPh苯腙苯腙CHCHOHNNHPh+NHNH2CHCONNHPhB.as Oxidant+C6H5NH2+NH3C.CHCONNHPh+NHNH2CHCNNHPhNNHPh脎脎 OsazoneSaccharidesCHOCHOH+NHNH2CHCNNHPhNNHPh3Epimer 差向异构体差向异构体CHCH2OHNNHPhHOOHOHNNHPh差向异构体形成相同的糖脎差向异构体形成相同的糖脎SaccharidesCHOCH2OHOHHOOHOHC

27、HOCH2OHHOHOOHOHCH2OHCH2OHHOOHOHOD-GlucoseD-MannoseD-Fructose.Oxidation:还原性糖还原性糖 reducing sugars弱氧化剂（碱性条件）弱氧化剂（碱性条件）CHOCH2OHOHHOOHOHAg+NH3/-OHCOO-CH2OHOHHOOHOH+AgCu2+COO-CH2OHOHHOOHOH+Cu2OTollens:Ag+(NH3)2OH-Fehling:Cu2SO4+OH-葡萄糖酸葡萄糖酸Saccharides非还原性糖非还原性糖Br2 /H2O(酸性条件）酸性条件）CHOCH2OHOHHOOHOHBr2/H2OCOOH

28、CH2OHOHHOOHOHOHOHOOHOHO葡萄糖酸-内酯Aldose(醛糖)OKetose(酮糖)OSaccharidesHNO3氧化氧化(酸性条件）酸性条件）CHOCH2OHOHHOOHOHHNO3COOHCOOHOHHOOHOHD-葡萄糖二酸葡萄糖二酸(Glucaric Acid)CHOCOOHOHHOOHOHOCOOHHOOHOHOH D-葡萄糖醛酸葡萄糖醛酸(glucuronic Acid)SaccharidesHIO4(高碘酸高碘酸)氧化氧化5HCOOH +HCHOSaccharides测定糖环结构测定糖环结构CHOCH2OHHOOHHIO45OHOHOHOOHOHOHOMeHI

29、O4OOHCOHCHOOHOMeHIO4OOHCOHCHOOMeHCO2H+邻二醇的氧化邻二醇的氧化.Reduction(还原反应还原反应)CO H COHCHOCH2OHOHHOOHOHH2/NiCH2OHCH2OHOHHOOHOH糖醇糖醇D-glucoseD-葡萄糖醇葡萄糖醇(山梨醇山梨醇)CH2OHCH2OHHOOHOHOCH2OHCH2OHOHHOOHOHCH2OHCH2OHHOHOOHOH+NaBH4D-FructoseD-Mannitol 甘露糖醇甘露糖醇SaccharidesSorbitolH2/Cat.NaBH4五五.Disaccharides&Polysaccharides(

30、二糖与多糖二糖与多糖)1.Disaccharides Moltose 麦芽糖麦芽糖OOHHOHOOHOOOHHOOHOH-1,4-糖苷键Maltose还原糖还原糖有变旋现象有变旋现象被氧化被氧化(Ag+,Cu2+,Br2/H2O)水解水解组成，糖苷键的特点组成，糖苷键的特点Saccharides淀粉酶解；食用饴糖，甜度为蔗糖的淀粉酶解；食用饴糖，甜度为蔗糖的40%Cellobiose 纤维二糖纤维二糖OOHHOHOOHOOOHHOOHOH-1,4-糖苷键Cellobiose还原糖还原糖有变旋现象有变旋现象被氧化被氧化(Ag+,Cu2+,Br2/H2O)水解水解组成，糖苷键特点组成，糖苷键特点纤

31、维素水解纤维素水解SaccharidesLactose 乳糖乳糖OOHHOHOOHOOOHHOOHOH-1,4-糖苷键Lactose还原糖还原糖有变旋现象有变旋现象被氧化被氧化(Ag+,Cu2+,Br2/H2O)水解水解组成，糖苷键特点组成，糖苷键特点乳糖的消化与吸收乳糖的消化与吸收乳糖酶与人种的差异乳糖酶与人种的差异Saccharides Sucrose 蔗糖蔗糖组成，糖苷键的特点组成，糖苷键的特点无变旋现象无变旋现象不能被氧化不能被氧化非还原糖非还原糖水解水解SaccharidesOOHOHHOOHOOHHOHOOHOSucrose-Saccharides2.Oligosaccharide

32、Cyclodextrin CD 环糊精环糊精种类、种类、-、-、-应用：药物制剂、分子识别、催化应用：药物制剂、分子识别、催化CH2OHCH2OHOH OHOHOHOHOHHOHOHOHOHOHO.OOOOOOOOOOOOHOO6 桶型结构桶型结构 上大下小上大下小 内径各异内径各异 外部亲水外部亲水 腔内亲脂腔内亲脂-1,4-糖苷键糖苷键3.Polysaccharides 多糖多糖纤维素纤维素 CelluloseOOHHOOHOOOHHOOHnCellulose-1,4-糖苷键组成，糖苷键特点组成，糖苷键特点线形多糖，线形多糖，n=1000 15000Saccharides 淀粉淀粉 Sta

33、rch直链淀粉直链淀粉 Amylose支链淀粉支链淀粉 AmylopectinOOHHOOHOOOHHOOHnAmylose-1,4-糖苷键250-300 D-GlucoseSaccharidesSaccharidesnAmylopectin-1,4-糖苷键-1,4-糖苷键OOHHOOHOOOHHOOHOOHHOOHOOOHOOH-1,6-糖苷键6000-40000 D-Glucose,20-25 个糖单元，一个分支个糖单元，一个分支支链淀粉支链淀粉 Amylopectin分子大小不同分子大小不同溶解度不同溶解度不同结构上的差异结构上的差异遇遇I2变色变色 糖原糖原 Glycogenn-1,4-糖苷键-1,4-糖苷键OOHHOOHOOOHHOOHOOHHOOHOOOHOOH-1,6-糖苷键8-10 单糖，出现一个分支单糖，出现一个分支组成、结构与支链淀粉类似组成、结构与支链淀粉类似增加溶解度及酶解速度增加溶解度及酶解速度Glycogen Saccharides