北大有机糖类化合物

1、Chapter 15 Saccharides 糖类化合物Saccharides (or Carbohydrates): 糖类; 碳水化合物衣，食，住，行 息息相关Starch (淀粉）：polysaccharides能量 来源Paper:cellulose(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 能量来源：葡萄糖、淀粉、糖原，ATP复杂的生物学功能重要的生命物质 影响蛋白质的折叠、溶解、半衰

2、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；Carbohydrate chemistry / Chemical glycobiologyGlycobiologyGeomics、Proteomics、Glycomics 糖类药物 (Carbohydrate Drugs)Saccharides血型物质与血型决定簇A型: Y=NHAcB型: Y= OHAB性: Y=NHAc or Y=OH O型ProteinOOOOOOHOHHOYOHOHOHHOOHH3CONHAcHOOHOXProteinOOOOHOHOHHOOHH3CONHAcHOOHOXHO血型 ？Saccharid

3、esOOSO3-HOHO-O3SHNOOHO2CHOOHOOOSO3-O3SHN-O3SOOOHOCO2HOSO3-OOHOOSO3-O3SHNOMe肝素五糖 ( Heparin Pentasaccharide)OHHOHOOHHNOH3CHOOHOOOHHOOHOOOHHOOHOH阿卡波糖 (Acarbose)OOOOOOSO2NH2 托吡酯 (Topiremate)糖类药物 (Carbohydrate Drugs)SaccharidesOR1R1NH2NH2OH2NHONHR2OOOHHOH2NOH卡那霉素 (Kanamycin ) R1=OH, R2=H敌拜卡霉素 (Dibekacin)

4、 R1=H, R2=H阿拜卡霉素 (Arbelkacin) R1=H, R2=COCH(OH)CH2CH2NH2OHOHOOHAcHNCO2HHNNH2NHRelenzaOOHHOHOOOMeHOHOOHOOHOOHAcHNOOHOOHOHOOHOOHHOOCeramideGlobo H 抗原OCO2HOHOAcHNHOHOOHHOOHOOHAcHNOOOHOHOOHOOHHOOCeramideGanglioside GM2糖类药物 (Carbohydrate Drugs)Saccharides一、 Definitions:1. Carbohydrates:多羟基的醛，多羟基的酮2. Mono

5、saccharides:最小的糖分子,不能水解3. Disaccharides:水解成两个单糖分子5. Polysaccharides:水解成多个单糖分子( 9)4. Oligosaccharides水解成多个单糖分子(2 9)二、 Classification:根据功能基Aldose (醛糖):Ketose(酮糖):SaccharidesCH2OHCCHHOCOHHCOHHCH2OHOCHOCCHHOCOHHCOHHCH2OHHOHGlucoseFructose根据C数丙糖 (triose)丁糖 (tetrose)戊糖 (pentose)D-ribose己糖 (hexose)GlucoseF

6、rucose根据氧化反应性质Reducing sugarNon-reducing sugar蔗糖SaccharidesSaccharides三、 Structure of Monosaccharides:1. 开链结构及构型(Chain Structures and Configurations)：具有多个手性中心，2n分子有旋光甘油醛：CHOCH2OHHOHCHOCH2OHHHOD-(+)-GlyceraldehydeL-(-)-Glyceraldehyde*CHOCOHHCH2OHCHOCCHHOCOHHCOHHCH2OHHOH*CH2OHCCHHOCOHHCOHHCH2OHO*Gluco

7、seFructoseSaccharides开链结构式的表示Fischer 投影式上下（氧化态）高低CHOOHHHHOOHHCH2OHOHHCHOHOHHOHHOHCH2OHHOH213456一对对映体D-GlucoseL-GlucoseSaccharides非对映异构体Epimer 差向异构体CHOOHHHHOOHHCH2OHOHH213456CHOOHHHHOHHOCH2OHOHH213456D-GlucoseD-MannoseCHOOHHHHOOHHCH2OHOHH213456CHOOHHOHHOHHCH2OHOHH213456D-GlucoseD-AlloseCHOOHHHHOOHHCH

8、2OHOHH213456CHOHHOHHOOHHCH2OHOHH213456D-GlucoseD-Galactose甘油醛：CHOCH2OHHOHCHOCH2OHHHOD-(+)-GlyceraldehydeL-(-)-GlyceraldehydeSaccharides糖构型表示法：D/L-Fischer 投影式；与甘油醛比较CHOOHHHHOOHHCH2OHOHHCHOHOHHOHHOHCH2OHHOH213456D-GlucoseL-GlucoseCHOOHHOOHCH2OHOHCHOCH2OH简化式SaccharidesHOHCHOCH2OHCH2OHOHHOHHCHOCH2OHHOHH

9、OHCHOCH2OHOHHOHHHOHCHOCH2OHOHHOHHHOHCHOCH2OHOHHHHOHOHCHOCH2OHHOHOHHOHHHOHCHOCH2OHHOHOHHOHHHOHCHOCH2OHHOHOHHHHOHOHCHOCH2OHHOHOHHHHOHOHCHOCH2OHHOHHHOOHHHOHCHOCH2OHHOHHHOOHHHOHCHOCH2OHHOHHHOHHOHOHCHOCH2OHHOHHHOHHOHOHCHOCH2OHOHHHHOHOHCHOD-GlyceraldehydeD-Erythrose (D-赤藓糖)D-Threose(D-苏糖)D-Ribose(D-核糖)D-A

10、rabinose(D-阿拉伯糖)D-Xylose(D-木糖)D-Lyxose(D-来苏糖) D-Allose(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D-， L-型糖互为一对对映体自然界存在的糖大多数都是D-型D. L. 只用在糖、 -氨基酸、 -羟基酸的构型表示SaccharidesSaccharides(1) Glucose + Tollens Glucose + Fehling

11、 Glucose + NaHSO3acetal实验现象RCHO+ 2CH3OHRCHOCH3OCH3dry HClC6H12O6+CH3OHdry HCl(C6H11O5)OCH3(2)(3) Mutarotation(变旋现象） +112 Glucose 溶液+52.7放置Saccharides +18.7 Glucose 溶液(4) IR, C=O; 1H NMR, COH异常现象？糖中的-CHO不是游离的，而是以半缩醛的形式存在。SaccharidesOHOHOOHOHOHOHOHOOHOHOHO -D-吡喃葡萄糖 -D-吡喃葡萄糖123456123456OOHHOHOOHOHOOHOH

12、OHHOHO -D-呋喃果糖 -D-呋喃果糖O123456123456Haworth 透视式糖环的编号 -、 -异构体的定义端基异构体(anomer)非对映异构体差向异构体2. Cyclic Structures and Conformations:Saccharides如何解释Mutarotation(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CHOCH2OHOHHHOHOHHOHHD-GlucoseFischer123456

13、OHOHOOHOHOHOHOHOOHOHOH-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Fischer投影式Haworth透视式 ？Fischer, 左侧基团Haworth，环上；右侧基团环下SaccharidesOHOHOOHOHOHOHOHOOHOHOH -D-吡

14、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Saccharides环状缩醛的形成：Saccharides吡

15、喃己醛糖吡喃戊醛糖&吡喃己酮糖OHOHOOHOHOH2134521345D-OHOOHOHOHOHL-Haworth式中构型的判断OOH2134521345L-OOHCH2OHD-呋喃己醛糖CHOHHOHHOOHHCH2OHOHHCHOOHCHHHHOOHHCH2OHOH*OOHOHOH*R-D-呋喃半乳糖端基异构体的确定C5- CH2OHC4-OH/C5-OHC5-构型 (R-, S-)SaccharidesOOHHOHOOHOHN式(I,4C1式），较稳定优势构象A式(II, 1C4式），不稳定OOHOHHOHOOH -D-GlucoseOOHHOHOOHOH -D-GlucoseConf

16、ormationsOHOHOOHOHOHOHOHOOHOHOHCHOCH2OHOHHHOHOHHOHH-, 36.4%-, 63.6%Anomeric EffectOOR-OOR-形成糖苷？SaccharidesC2C6羟基取代时：(端基效应)溶剂的作用：极性溶剂非极性溶剂CCH2OHOHOHHOOHOHD-Glucose.OHHOOHCCH2OHOHHO-D-(+)-GlucoseOCH2OHHOOHOHOHorOOHHOHOOHOHorOHHOOHCCH2OHHOHO-D-(+)-GlucoseorOCH2OHHOOHOHOHOOHHOHOOHOHorSaccharidesSacchari

17、desCH2OHHOHOHHHHOHOHCHOOCH2OHHOOHOHOHOOHHOHOOHOHCH2OHHOHHHOHHOHOHCHOOCH2OHHOOHOHOHOOHHOHOOHOHCH2OHHOHOHHHHOHOHCHOOCH2OHHOOHHOOHOOHHOHOOHOHD-GlucoseD-GalactoseD-MannoseSaccharidesCH2OHOHHOHHHOHCHOOHOOHOHOHCH2OHOHHOHHHHCHOOHOOHOHCH2OHHOHOHHHHOOCH2OHOHOOHHOOHOHOHOOHHOOHOHD-FructoseD-Ribose2-Deoxy-D-rib

18、ose3、Chemical Reaction:-CHO: Nucleophilic Addition Oxidation, Reduction-OH: 酯化，醚化，脱水复合性质（各基团相互影响）-特性CHOCH2OHOHHOOHOHD-GlucoseSaccharides . Formation of glycosides 糖的成苷反应 糖的环状半缩醛或半缩酮形式Acetal or Ketal 成苷反应，糖苷 Glycosides OOHHOHOOHOHCH3OHDry HClD-GlucoseOOHHOHOOHOMeOOHHOHOOHOMe+Methyl -D-glucoside Methy

19、l -D-glucoside SaccharidesOORROROORX+Glycosyl donorHYCatalystSolventTemperatureOORROROORYHY = HOR, HSR, HNRR, HCAcceptorYieldSelectivityAvailabilitySaccharides糖苷的性质稳定，无变旋现象碱性条件稳定稀酸或酶的作用NHOHOHOOHOHOOHOHOOHOHSCNCH2CHCH2OSO3K硫苷 (芥子苷)OOHHONNHOOH3CHNNHOOOOHHOOH氧苷(尿兰母)氮苷 (脱氧胸苷)碳苷 (伪尿嘧啶核苷)OOHHOHOOHXRglycos

20、idic bondglycosyl partaglycon, geninOHOHOOHOHOOHOCH2HOOHOHOOHOHOOHOHOCHCN水杨苷，解热镇痛OHOHOOHOHOCH2OH熊果苷尿道消毒皮肤增白剂苦杏仁苷毒性SaccharidesProteinOOOOHOHOHHOOHH3CONHAcHOOHOXHO . Esterification (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OHOHOOH

21、OHOH+(CH3CO)2OH3CCClOOAcOAcOOAcOAcOAcSaccharides条件：弱碱KOAc, Pyridine保护基CHOCH2OPOHOHOOHHOOHOH6-磷酸-D-GlucoseCH2HOOHOPOHOHO磷酸甘油酯 . 醚化反应SaccharidesOHOOHOHOHOHCH3IAg2OOH3COH3COOCH3OCH3OCH385%Williamson 醚合成法OOHHOHOOHOMeMethyl -D-glucopyranoside OOHHOHOOHOHCH3OHdry HClOOHHOHOOHOMe+Me2SO4NaOH稀HClOOMeMeOMeOOM

22、eOHOOMeMeOMeOOMeOMeOOHHOHOOHOMeSaccharides . 环缩醛、酮的生成1, 2-diol or 1, 3-diolCis-OOHOHHOOHOH+CH3CCH3O2OOHOOOOH3CH3CH3CCH3H2SO4OOHHOHOOHOCH3+PhCHOOOOHOOHOCH3PhH+糖化学中羟基的保护SaccharidesCH2OHCHOHOHOOHHOD-GlucoseH2/NiCH2OHCH2OHHOHOOHHOO黑醋酸菌CH2OHCH2OHHOOHHOOL-SorboseOOHOHOHHOHOAcetone/H2SO4OOOHOOONaOCl/NaOHHC

23、lOOHOHOHHOHOOOOHOHOHHOHOOHOOHOHOHOVitamin C (Ascorbic Acid) . Dehydration ( 脱水):CHOCH2OHOHOHOHH+OCHOHOHOOCHOD-核糖-呋喃甲醛（糠醛）CHOCH2OHOHOHOHOHH+OCHOHOHOCH2OHOCHOCH2OHD-阿洛糖5-羟甲基-呋喃甲醛Saccharides . Epimerism 差向异构化糖与碱的作用CHOCH2OHOHHHOOHOHD-GlucoseB*CHOHCOHCH2OHOHOHHO烯醇式CHOCH2OHOHHOOHOHD-Glucosea*CHOCH2OHHOHOO

24、HOHD-Mannoseb*CH2OHCH2OHHOOHOHOD-FructosecSaccharidesD-Glucose碱水溶液D-glucose+D-Mannose+ D-Fructose . Formation of Osazone Epimers 糖脎的形成 /差向异构体CHOCHOH+NHNH2A.CHCHOHNNHPh苯腙CHCHOHNNHPh+NHNH2CHCONNHPhB.as Oxidant+C6H5NH2+NH3C.CHCONNHPh+NHNH2CHCNNHPhNNHPh脎 OsazoneSaccharidesCHOCHOH+NHNH2CHCNNHPhNNHPh3Epim

25、er 差向异构体CHCH2OHNNHPhHOOHOHNNHPh差向异构体形成相同的糖脎SaccharidesCHOCH2OHOHHOOHOHCHOCH2OHHOHOOHOHCH2OHCH2OHHOOHOHOD-GlucoseD-MannoseD-Fructose . Oxidation:还原性糖 reducing sugars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Saccha

26、rides非还原性糖Br2 / H2O (酸性条件） CHOCH2OHOHHOOHOHBr2/H2OCOOHCH2OHOHHOOHOHOHOHOOHOHO葡萄糖酸-内酯Aldose(醛糖)OKetose(酮糖)OSaccharidesHNO3氧化(酸性条件） CHOCH2OHOHHOOHOHHNO3COOHCOOHOHHOOHOHD-葡萄糖二酸(Glucaric Acid)CHOCOOHOHHOOHOHOCOOHHOOHOHOH D-葡萄糖醛酸(glucuronic Acid)SaccharidesHIO4 (高碘酸)氧化5HCOOH + HCHOSaccharides测定糖环结构CHOCH2

27、OHHOOHHIO45OHOHOHOOHOHOHOMeHIO4OOHCOHCHOOHOMeHIO4OOHCOHCHOOMeHCO2H+邻二醇的氧化 . Reduction (还原反应)CO H COHCHOCH2OHOHHOOHOHH2 / NiCH2OHCH2OHOHHOOHOH糖醇D-glucoseD-葡萄糖醇 (山梨醇)CH2OHCH2OHHOOHOHOCH2OHCH2OHOHHOOHOHCH2OHCH2OHHOHOOHOH+NaBH4D-FructoseD-Mannitol 甘露糖醇SaccharidesSorbitolH2/Cat.NaBH4五. Disaccharides & Po

28、lysaccharides (二糖与多糖)1. Disaccharides Moltose 麦芽糖OOHHOHOOHOOOHHOOHOH-1,4-糖苷键Maltose还原糖有变旋现象被氧化(Ag+,Cu2+, Br2/H2O)水解组成，糖苷键的特点Saccharides淀粉酶解；食用饴糖，甜度为蔗糖的40% Cellobiose 纤维二糖OOHHOHOOHOOOHHOOHOH-1,4-糖苷键Cellobiose还原糖有变旋现象被氧化(Ag+,Cu2+, Br2/H2O)水解组成，糖苷键特点纤维素水解SaccharidesLactose 乳糖OOHHOHOOHOOOHHOOHOH-1,4-糖苷键

29、Lactose还原糖有变旋现象被氧化(Ag+,Cu2+, Br2/H2O)水解组成，糖苷键特点乳糖的消化与吸收乳糖酶与人种的差异Saccharides Sucrose 蔗糖组成，糖苷键的特点无变旋现象不能被氧化非还原糖水解SaccharidesOOHOHHOOHOOHHOHOOHOSucrose - -Saccharides2. OligosaccharideCyclodextrin CD 环糊精种类、 -、 -、 -应用：药物制剂、分子识别、催化CH2OHCH2OH.OH OHOHOHOHOHHOHOHOHOHOHO.OOOOOOOOOOOOHOO6 桶型结构 上大下小 内径各异 外部亲水

30、腔内亲脂 -1, 4-糖苷键3. Polysaccharides 多糖纤维素 CelluloseOOHHOOHOOOHHOOHnCellulose-1,4-糖苷键组成，糖苷键特点线形多糖，n= 1000 15000Saccharides 淀粉 Starch直链淀粉 Amylose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6000-400

31、00 D-Glucose, 20-25 个糖单元，一个分支支链淀粉 Amylopectin分子大小不同溶解度不同结构上的差异遇I2变色 糖原 Glycogenn-1,4-糖苷键-1,4-糖苷键OOHHOOHOOOHHOOHOOHHOOHOOOHOOH -1,6-糖苷键8-10 单糖，出现一个分支组成、结构与支链淀粉类似增加溶解度及酶解速度Glycogen Saccharides二、 Classification:根据功能基Aldose (醛糖):Ketose(酮糖):SaccharidesCH2OHCCHHOCOHHCOHHCH2OHOCHOCCHHOCOHHCOHHCH2OHHOHGlucoseFructose根据C数丙糖 (triose)丁糖 (tetrose)戊糖 (pentose)D-ribose己糖 (hexose)GlucoseFrucoseSaccharides非对映异构体Epimer 差向异构体CHOOHHHHOOHHCH2OHOHH213456CHOOHHHHOHHOCH