ChapterChapter 24:24: CarbohydratesCarbohydrates PhotosynthesisPhotosynthesis:: EnergyEnergy storagestorage

Sun, chlorophyll 6 CO2 + 6 H2O C6(H2O)6 + 6 O2 Metabolism Glucose Land plants Universal

ChlorophyllChlorophyll 3% to 6% of the total incident solar radiation is used for

chemical conversion of H2O (oxidation to O2) and CO2 (reduction to glucose). CarbohydrateCarbohydrate == CCn(H(H2O)O)n Hydrated carbon

CarbohydratesCarbohydrates occuroccur inin naturenature inin nucleicnucleic acids,acids, fats,fats, cellulose,cellulose, fibers,fibers, starch,starch, “table“table sugar,”sugar,” antibiotics,antibiotics, andand otherother biologicalbiological molecules.molecules.

A pentahydroxyaldehyde NamingNaming TheThe simplestsimplest carbohydratescarbohydrates areare thethe sugarssugars oror saccharidessaccharides.. TheyThey constituteconstitute polyhydroxypolyhydroxy-- aldehydesaldehydes ((aldosesaldoses)) oror --ketonesketones ((ketosesketoses);); theythey formform oligomersoligomers byby etherether bridgesbridges (hence(hence didi--,, tritri--,, tetrasaccharidetetrasaccharide,, etc.).etc.).

The simplest sugars, both

C3(H2O)3:

2,3-Dihydroxypropanal 1,3-Dihydroxyacetone Chiral (Glyceraldehyde) A ketotriose An aldotriose

ChainChain lengthlength:: TriTrioseose,, tetrtetroseose,, pentpentose,ose, etc.etc. SomeSome importantimportant monomonosaccharidessaccharides::

*

* 4 Stereo- * 3 Stereo- * * centers * centers * * * *

Dextrose, blood sugar, grape sugar Sweetest natural sugar; fruits Ribonucleic acids

Fischer projections: Review chapter 5 FischerFischer Projection:Projection: AA flatflat stencilstencil

Br H BrBr CCHH3 CC CCHH2CCHH3 HH BrBr Rules reminder: CH CH 180 º turn or double CCHH3 CH2CH3 Eyes in the exchange leaves plane of the stereochemistry intact HH board

DependingDepending onon youryour startingstarting dasheddashed--wedgedwedged lineline structure,structure, severalseveral FischerFischer projectionsprojections areare possiblepossible forfor thethe samesame molecule.molecule. MostMost sugarssugars areare chiralchiral andand occuroccur enantiomericallyenantiomerically pure.pure. SimplestSimplest case,case, oneone stereocenter:stereocenter:

D and L is an older nomenclature (predates the knowledge of the absolute configuration of glyceraldehyde). The dextrorotatory enantiomer was called D, the other L. Later, D was found to be R, L therefore S.

Almost all natural sugars have stereocenter furthest away from carbonyl (drawn at the bottom) with the same absolute configuration as D-glyceraldehyde: “D-sugars” Rules for arranging the Fischer stencil: Carbonyl on top, places bottom C*OH on the right in the D sugars.

Natural Unnatural

D-Erythrose L-Erythrose D-Threose L-Threose TheThe FamilyFamily ofof NaturalNatural AldosesAldoses TheThe FamilyFamily ofof NaturalNatural KetosesKetoses Fischer Projections and Dashed-Wedged Line Structures Recall: Fischer projections represent an unrealistic model of the molecule: All eclipsed; carbon chain “curves”. It’s usefulness is in stereochemical bookkeeping.

DD--GlucoseGlucose Five- Six- membered membered ring ring

Two diaste- Two diastereomers: reomers: Anomers Anomers

HaworthHaworth StructuresStructures Groups that lie on the right in the Fischer projection point downward in the Haworth projection.

At the anomeric carbon: OH down is called the α-anomer, OH up is called the β-anomer. OtherOther waysways ofof drawingdrawing cycliccyclic structures:structures:

Not a carbon atom BestBest areare conformationalconformational pictures:pictures:

Anomeric Anomeric carbon carbon

OH down: α-Anomer; OH up: β-Anomer; crystallizes more stable because all-equatorial MutarotationMutarotation:: ChangeChange inin observedobserved opticaloptical rotationrotation whenwhen aa sugarsugar moleculemolecule equilibratesequilibrates withwith itsits anomeranomer.. ReactionsReactions ofof SugarsSugars 1.1. OxidationOxidation a.a. CHOCHO ÆÆ COOHCOOH ((aldosealdose ÆÆ aldonicaldonic acidacid))

b.b. αα--HydroxyHydroxy groupgroup ofof ketosesketoses ÆÆ αα--dicarbonyldicarbonyl

Tests for “reducing” sugars; all ordinary saccharides are reducing. LargeLarge scalescale preparationpreparation ofof aldonicaldonic acids:acids: BrBr2,, HH2OO

Dehydration gives lactones, typically five-membered (γ- lactones).

Mechanism of bromine oxidation: H O R R : O O H O, H+ Br : RCH 2 H C OH 2 Br Br H C O H H RCHOH OH OH c.c. OxidationOxidation ofof bothboth endsends ofof aldosesaldoses →→ aldaricaldaric acidacid

Note selectivity of nitric acid: Picks on primary OH function (after oxidizing the formyl group): Less hindered.

Mechanism: O O H O H2O, HO-NO2 N RCH O O RCOH + HO-NO

:O: : C Nitrous acid R H For some sugars, this oxidation may give meso (achiral) aldaric acid. Can be used for proof of stereochemistry.

CHO COOH H OH H OH H OH HNO3 H OH Mirror plane H OH H OH H OH H OH

CH2OH COOH

D-(+)-Allose Allaric acid (meso) Symmetry becomes obvious also in NMR, e.g. 13C NMR:

6 peaks 3 peaks d.d. OxidativeOxidative cleavage:cleavage: HIOHIO4

This reagent causes the rupture of vicinal diols to dialdehydes. How? Does this ring a bell? Remember OsO4 oxidation of alkenes to vicinal diols: Cleaves “half” a double bond.

HIO4 does the same to a single bond (bearing OHs). Similarly: Remember benzylic oxidation of alkylbenzenes to benzenecarboxylic acids by basic KMnO4. O O Mn

O :O: : K •• CC--CC bondbond brokenbroken via:via:

OH O OH

KMnO4 does both the OsO4-type and HIO4-type oxidations sequentially in the same reaction step. How does this work for sugars? Leads to complete degradation of the carbon chain.

H H H OH CHO HO C OH HO C O C I O HO O HIO H OH HOH H OH 4 H O O H O H OH H OH H OH H OH

Note: Each carbon fragment retains the same number of attached hydrogen atoms as were present in the original sugar. AnotherAnother wayway toto thinkthink aboutabout thisthis isis asas aa ““dihydroxylativedihydroxylative”” cleavagecleavage ofof eacheach chainchain CC--CC bond,bond, e.g.e.g. fructose:fructose:

OH Add OHs to each side ½½ OH of the bond broken OH ½½ OH OH ½½ OH OH ½½ OH OH ½½ OH

Note: Each carbon fragment retains the same number of attached hydrogen atoms as were present in the original sugar. 2.2. ReductionReduction toto alditolsalditols

Note: Just as in the oxidation to aldaric acids, reduction may symmetrize the sugar.

Sorbitol (“sugar alcohol”) is used as artificial sweetener in diet foods: 2.6 cal/g per versus 4 cal/g for normal sugar. Sorbitol also occurs naturally in many stone fruits. 3.3. EstersEsters andand Ethers:Ethers: ProtectionProtection

Hemiacetal Acetal

Acetal function can be deprotected selectively Mild, does not touch normal ether

Alternative exploitation of the special reactivity of the (hemi)acetal function: Turn it into an acetal, called glycoside for sugars.

Protection of anomeric carbon Æ no mutarotation, no aldehyde oxidation (i.e. does not behave as reducing sugar), no reduction. ProtectionProtection asas cycliccyclic acetalsacetals

Recall:Recall:

-CH2OH often not engaged: Flexibility makes entropy of acetal formation worse

OH OH H3C H H CH3 HO O O O O + O HO , H O H OH H H H H H H3C OH H O H H3C

β-D-Altrose β-D-Altrose bisacetonide 4.4. KilianiKiliani--FischerFischer ExtensionExtension (Modified)(Modified)

Heinrich Kiliani 1855 - 1945

Emil Fischer 1852-1919 Lindlar type Example:Example:

CHO CHO CHO 1. HCN HO H H OH 2. H2, HO H Pd-BaSO4, H O, H+ HO H HO H HO H 2 + HO H HO H H OH H OH H OH CH2OH CH2OH CH2OH D-Lyxose D-Lyxose D-Talose D-Galactose 5.5. RuffRuff DegradationDegradation

Note: Both diastereomers (R or S at the top stereocenter) degrade to the same lower sugar.

Fe3+Æ Fe2+ Fe3+Æ Fe2+ StructureStructure DeterminationDetermination ofof SugarsSugars-- TheThe FischerFischer ProofProof LogicalLogical combinationcombination ofof 1.1. SugarSugar extensionextension →→ 22 diastereomersdiastereomers 2.2. SugarSugar degradation:degradation: 22 DiastereomersDiastereomers givegive samesame sugar)sugar) 3.3. SugarSugar symmetrizationsymmetrization viavia aldaricaldaric acidsacids oror alditolsalditols 4.4. RecognitionRecognition ofof intricateintricate stereochemicalstereochemical relationshipsrelationships AA glimpseglimpse atat thethe logic:logic:

Ext. Ext. Oxn. or Oxn. or Redn. Redn. Achiral Chiral

Etc. Etc.

Oxn. or Oxn. or Redn. Redn. Same compound CHO CH2OH CH2OH CHO HO H HO H HO H HO H H OH H OH HO H HO H H OH H OH H OH H OH

CH2OH CH2OH CH2OH CH2OH

D-Arabinose Same! D-Lyxose

CHO COOH COOH CHO H OH H OH H OH H OH HO H HO H H OH H OH H OH H OH HO H HO H H OH H OH H OH H OH

CH2OH COOH COOH CH2OH

D-Glucaric acid D-Gularic acid Enantiomers DD--KetosesKetoses correlatecorrelate withwith alditolsalditols byby reductionreduction

E.g., Again, potential symmetrization Alditols of symmetrization erythrose and helps in threose structural assignment

Alditols of glucose and mannose DiDi-- andand HigherHigher SaccharidesSaccharides Sucrose:Sucrose: DisaccharideDisaccharide derivedderived fromfrom glucoseglucose andand fructosefructose 150 lb/ person/ year “Table sugar”

Ether bridge between respective anomeric centers: Nonreducing [α]D = +66.5

[α]D = -20 LactoseLactose (milk(milk sugar)sugar)

Ether bridge between anomeric C and C4

β Reducing α C4 Cellulose:Cellulose: SugarSugar PolymerPolymer

Molecular weight 500,000 (~3000 units) 1 unit = 178 molecular weight. Used in cell wall material: Rigid structure due to multiple hydrogen bonds. Nitrocellulose:Nitrocellulose: ExplosiveExplosive Major component of smokeless gunpowder (guncotton); used in photographic film.

Christian F. Schönbein 1799-1868

Henri Braconnot:

1832: HNO3 + starch Théophile-Jules Pelouze:

1838: HNO3 + paper Starch:Starch: PolyglucosePolyglucose withwith αα––acetalacetal linkslinks Constitutes fuel reserve in plants: Corn, potatoes, wheat (bread), rice. Hydrolyzes to glucose (sweat taste of bread in mouth). Two major components: AmyloseAmylose AmylopectinAmylopectin (has(has branches)branches) HumanHuman FuelFuel Tank:Tank: GlycogenGlycogen

Provides immediate glucose during strain

MW = 100 million SugarsSugars asas waterwater solubilizingsolubilizing groupsgroups inin nature:nature: AnthracyclineAnthracycline anticanceranticancer agentsagents andand antibioticsantibiotics

Anthracycline Anthracycline Streptomycin intercalates into intercalates into binds to the DNA: Kills (tumor) DNA: Kills (tumor) ribosome, causes cells cells misreading of genetic information