The R,S system was adopted for sugars and, by coincidence, the D-isomer was determined to have the R-configuration as drawn by Fischer! (R)-glyceraldehyde (S)-glyceraldehyde CHO CHO HO H H OH CH2OH CH2OH 25 α 25 o α = +13.5 o D = -13.5 D levrorotatory isomer dextrorotatory isomer L-glyceraldehyde D-glyceraldehyde Now glyceraldehyde serves as a reference for all other carbohydrates: The penultimate carbon is the highest numbered carbon (using conventional rules for nomenclature). The penultimate carbon is the stereocenter lowest on the backbone. • At the penultimate carbon, all D-sugars have the OH group on the right; the same configuration as D-glyceraldehyde. • There is no correlation between D and L with R and S! • A sugar with R configuration at the penultimate carbon may rotate P-P light to the right or the left; i.e., it may be a D or an L sugar. The most abundant monosaccharide is D-glucose. Recall: aldehydes + alcohol → hemiacetal Glucose cyclizes into a hemiacetal using the penultimate OH group as the alcohol. The result is a cyclic hemiacetal. These structures are called Haworth formulas. CHO anomeric carbon hemiacetal CH OH A CH OH CH2OH H OH 2 2 H H H O OH HO H OH H O H H OH H H OH OH O OH H H OH OH OH OH OH H H OH H OH CH2OH B H OH O α-D-glucose β-D-glucose D-glucose pyran α-D-glucopyranose β-D-glucopyranose alpha = axial beta = equatorial Stereoisomers that differ in configuration at the anomeric center are called anomers. The anomeric carbon of aldoses is C-1 and the anomeric carbon of ketoses is C-2 α-D-glucose and β-D-glucose are anomers. Conversion of Fischer projection into Haworth formula and then into chair. C-1 CHO C-5 squiggle line means O C-1 OH is up or down; i.e.; H OH C-4 OH tip over to the right C-3 C-2 α or β is not specified. HO H so aldehyde at C-1 H OH (anomeric carbon) cyclize into hemiacetal by drawing H OH ends up on the right six-membered ring and place the oxygen side of Haworth atom in upper right "corner" of Haworth C-6 CH2OH Now add the OH and H atoms on the ring. If the OH is on the right side of Fischer then it ends up “down” in Haworth. Only consider OH at C-2, C-3 and C-4; the OH group at C-5 is part of the acetal. The C-6 carbon (CH2OH group) is always drawn “up” in Haworth. CH2OH O Finally, add the H atoms to OH OH OH group at C-3 complete the structure. is on the left so it OH CH2OH goes "up" in OH H O Haworth OH H OH CHO OH groups at C-2 and OH H OH H OH C-4 are on the right so they go "down" in HO H Haworth H OH H OH C-6 always goes "up" in Haworth (outside or above the ring) CH2OH To form chair, move “end” carbons: C-4 CH2OH CH2OH HO O H O H pull C-4 up OH H drag C-1 down HO C-1 OH OH OH (this is the α−anomer) H OH OH Notice that OH groups (and CH2OH group at C-6) are all equatorial positions. OH group at C-1 is axial in the α-D-glucopyranose and equatorial in β-anomer. H CH2OH HO O Finish structure by H adding hydrogen atoms HO H H OH OH Mutarotation- equilibration between α and β hemiacetals. mutarotation shown for glucose CH2OH CH2OH CH2OH H H H OH O H OH H O OH H OH H O OH H OH OH OH OH H H OH H OH H OH The hemiacetals are in equilibrium with open-chain aldehyde. Galactose- one more important monosaccharide. D-galactose CHO CH2OH OH H OH O H H Similar to glucose except for HO H OH α-D-galactose configuration at C-4 H OH HO H H OH H OH CH2OH Fructose is another abundant monosaccharide- it is a ketohexose. CH2OH O D-fructose O furan HO H cyclic hemiacetal formation gives a furanose H OH H OH furanose hemiacetals exists as anomers CH2OH A CH OH CH2OH O 2 O CH2OH CH OH CH OH OH OH 2 2 HO H HO H OH H O H OH H H CH2OH B OH OH OH H H H α-D-fructose β-D-fructose α-D-fructofuranose β-D-fructofuranose Fructose also exists in the pyranose form- cyclization of OH group at C-5. CH2OH CH2OH HO HO HO H HO H O D-fructofuranose H OH H OH O D-fructopyranose H H OH CH CH2OH 2 Glycosides- cyclic acetals Treatment of monosaccharide with alcohol gives cyclic acetal. Monosaccharides exist mostly in hemiacetal form; conversion to acetal occurs easily: Either anomer gives the same equilibrium mixture of glycosides H CH2OH H H CH2OH CH2OH O CH OH, H+ HO 3 HO O HO O H H H HO HO H HO H + OCH OH + 3 H H2O, H H OH H OH H OH methyl α-D-glucopyranoside OCH3 methyl β-D-glucopyranoside “ose” suffix- hemiacetal (may be open-chain aldehyde or ketone) “oside” suffix- acetal An aglycone is the group bonded to the anomeric carbon atom of a glycoside; in the example above, methanol is the aglycone. NH2 salicin (from willow bark) N aglycone CH2OH O H CH OH N O 2 H HO O H H HO O CH2OH H H H OH OH OH H cytidine, a nucleoside aglycone Mutarotation is not possible since acetals are not in equilibrium with open-chain form. Glycosides are stable in base like any acetal but easily hydrolyze in acid. Reactions of monosaccharides 1. Epimerization and isomerization in base- mostly useless 2. Reduction of aldehydes and ketones- alditols 3. Oxidation-aldonic acids and aldaric acids 4. Formation of ethers and esters 5. Reactions with phenylhydrazine- osazones 6. Chain-shortening- Ruff degradation 7. Chain-lengthening- Kiliani-Fischer synthesis 1. Reactions with base- epimerization and isomerization Base removes the alpha proton. This is a reversible step and epimerization will occur: H O H O H O H O H+ base: H OH OH OH HO H HO H HO H HO H HO H H OH H OH H OH H OH H OH H OH H OH H OH CH OH CH2OH 2 CH2OH CH2OH epimer Deprotonation forms the enolate which may also undergo a rearrangement: HOH H O H OH OH OH H HOH OH H H OH OH OH O O HO H HO H O HO H HO H H OH H OH HO H H OH H OH H OH H OH H OH H OH H OH H OH CH2OH CH2OH CH2OH CH OH CH OH D-glucose enolate 2 2 D-fructose This is called the enediol rearrangement. 2. Reduction of aldehydes and ketones- alditols Reduction of an aldose: H O H OH CH2OH H NaBH4 An alditol H OH H OH O or HO H HO H HO H glucitol aka sorbitol HO H OH H2, Ni H OH OH H OH H OH H OH CH2OH CH2OH Reduction of a ketose gives epimers at C-2: CH2OH CH2OH CHO CH2OH H OH HO H HO H O NaBH HO H HO H 4 HO H NaBH4 + HO H H OH H OH H OH H OH H OH H OH H OH H OH CH2OH CH2OH CH2OH CH2OH glucitol mannitol mannose Notice that mannose and fructose provide mannitol. Reduction may disclose latent remaining symmetry- reduction of allose gives an optically inactive alditol: CHO CH2OH H OH H OH H OH NaBH H OH optically 4 inactive H OH H OH H OH H OH CH OH CH2OH 2 allose 3. Oxidation-aldonic acids and aldaric acids Two sites of oxidation: Aldehyde terminal CH2OH group • Bromine water oxidizes aldoses: O OH CHO CO2H CHO C H OH H OH H OH HO H Br2 HO H H OH Br2 H OH H O H OH HO H HO H 2 H2O H OH H OH CH2OH CH OH CH2OH CH2OH 2 aldonic acid aldose gluconic acid Bromine water 9 does not oxidize ketoses 9 does not oxidize other CH2OH groups 9 does not cause epimerization or rearrangement of carbonyl group. • Nitric acid oxidizes both aldehyde and terminal CH2OH group. CHO CO2H O OH H OH CHO C H OH HO H HO H H OH HNO H OH HNO3 3 H OH H OH HO H HO H H OH H OH CH OH CO H 2 C CH2OH 2 aldose O OH glucaric acid aldaric acid Tollen’s Test- Tollen’s reagent oxidizes aldehyde to carboxylate and produces metallic silver. O O 2 Ag(NH ) + OH- C + Ag(s) + 4 NH + 2 H O C 3 2 3 2 R O R H Due to the basic conditions cause epimerization and enediol rearragements. Sugars that reduce Tollen’s reagent are called reducing sugars. Since a ketose will rearrange to an aldehyde, it is also a reducing sugar. H OH H O O O CH2OH C C C - + - - OH Ag(NH3)2 OH O OH OH H OH H OH HO H HO H HO H HO H CH OH CH OH CH OH 2 2 CH2OH 2 Glycosides are acetals and are non-reducing sugars.