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Title The Carbohydrates [C(H2O)]n Emil Hermann Fischer ( )
![Title The Carbohydrates [C(H2O)]n Emil Hermann Fischer ( )](http://slideplayer.com./slide/5046750/16/images/1/Title+The+Carbohydrates+%5BC%28H2O%29%5Dn+Emil+Hermann+Fischer+%28+%29.jpg "Title The Carbohydrates [C(H2O)]n Emil Hermann Fischer ( )")
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F-R Convention The Fischer-Rosanoff Convention CHO C2-OH C3-OH C4-OH
C6-CH2OH
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D/L Series Fischer-Rosanoff D- and L-Series
OH on the right of the highest numbered chiral carbon = D-series. OH on the left of the highest numbered chiral carbon = L-series.
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D-Aldohexoses The D-Aldohexoses 2 right 8 right 2 left C3 2 right
Allose Altrose Glucose Mannose Gulose Galactose Idose Talose All altruists gladly make gum in gallon tanks [L. Fieser]
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Rxn of Aldoses Reactions of Aldoses osazone CHO OH CH2OH + PhNH2 + NH3
=N-NHPh CH2OH OH osazone OH HO CHO CH2OH 3 equiv. PhNHNH2 CO2H OH aldaric acid HO HNO3 achiral alditol OH CH2OH NaBH4 HO achiral CO2H OH CH2OH aldonic acid Br2/H2O HO
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Osazones More on Osazones CHO OH CH2OH HO D-glucose OH CH2OH HO
D-fructose O OH HO CHO CH2OH D-mannose Ca(OH)2 (Lobry de Bruyn- Alberda van Eckenstein rearrangement, 1895) 3 equiv. PhNHNH2 1 equiv. PhNHNH2 =N-NHPh OH CH2OH HO D-glucose phenylhydrazone OH HO =N-NHPh CH2OH D-mannose phenylhydrazone 1 equiv. PhNHNH2 + PhNH2 + NH3 2 equiv. PhNHNH2 =N-NHPh CH2OH OH HO
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F-K and Ruff Chain Lengthening and Shortening of Aldoses OH HO CN
CH2OH HCN Fischer-Kiliani Synthesis OH CH2OH CHO Fe+++ H2O2 Ruff Degradation Pd/BaSO4 pH 4.5, H2 CHO OH CH2OH HO CO2Ca1/2 OH CH2OH HO Br2/H2O Aldonic acid as Ca salt
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D-Series Interrelationship
Interrelationship of the D-Series of Aldoses via Chain Lengthening and Degradation
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Which one is Glucose? The Aldohexoses But which one is (+)-glucose?
D-series L-series
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Aldaric Acids/Alditols
Rosanoff Formulation of C6 Aldaric Acids and Alditols Terminal groups identical; CO2H or CH2OH
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Fischer Proof: 1 X Fischer’s Proof: Part 1
(+)-Glucose forms an optically active aldaric acid and optically active alditol. 1, 7, 9, 15 eliminated: plane of symmetry, achiral X 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
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Fischer Proof:2 X X Fischer’s Proof: Part 2
(+)-Glucose and (+)-mannose form the same osazone. If 1, 7, 9, and 15 are not related to (+)-glucose, then they are not related to (+)-mannose nor are 2, 8, 10, and 16 related to (+)-glucose. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 X X
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Fischer Proof:3 Fischer’s Proof: Part 3
(+)-Arabinose affords (-)-glucose and (-)-mannose by Kiliani-Fischer synthesis. (+)-Arabinose must be of the opposite series (D/L)as (+)-glucose and have the same absolute configuration at C3-5 as (-)-glucose and (-)-mannose. What is the structure of arabinose?
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F P:3, con’t X Arabinose is either or
(+)-Glucose is one of these structures Arabinose forms an optically active aldaric acid (arabinaric acid) and optically active alditol (arabitol) Arabinose is
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Fischer Proof:4 X Fischer’s Proof: Part 4
The pentose (+)-xylose affords optically inactive xylaric acid and optically inactive xylitol as its borax complex. (+)-Xylose can only be one of the following: X These enantiomers cannot be (+)-xylose because their Fischer-Kiliani hexoses (already eliminated) would lead to one optically active and one optically inactive aldaric acid. Fischer-Kiliani synthesis of (+)-xylose leads to two new hexoses, (+)-gulose and (+)-idose, both of which form optically active aldaric acids. (+)-Xylose must be one of the remaining two structures.
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Fischer Proof:5 Fischer’s Proof: Part 5 (+)-Arabinose
(+)-Xylose (+)-Gulose/(+)-Idose (+)-Glucose/(+)-Mannose
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or Fischer Proof:5, con’t Fischer’s Proof: Part 5
(+)-Glucose and (-)-gulose form the same optically active aldaric acid, glucaric acid. identical or (+)-Glucose must be either identical
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Fischer Proof:5, con’t-2 Fischer’s Proof: Part 5
(+)-Mannose must be one of these hexoses, the C2 epimer of (+)-glucose. rotate 180o identical mannaric acid rotate 180o identical Mannaric acid is formed from a single hexose.
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Fischer Proof:6 Fischer’s Proof: Part 6
But which enantiomer of glucose is (+)-glucose? D-glucose L-glucose Just Guess! Fischer arbitrarily assigned the D-series to the dextrorotatory enantiomer. Sixty years later (1951), he was proved correct when Bijvoet related (+)-glucose to (+)-tartaric acid. Fischer: All sugars related to D-(+)-glucose by chemical correlation belong to the D-series.
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Fischer’s Flaw A Flaw in the Fischer Scheme
(+)-Glucose (-)-Glucose (-)-Galactose (+)-Galactose Identical Achiral Mucic Acid (An Aldaric Acid) "Two aldoses can produce the same dibasic acid only if they belong to the same stereochemical family. That this, however, is erroneous as a general proposition, may be readily seen from the fact that the two enantiomorphous galactoses - plainly belong to the opposite families - yield the same mucic acid.” A. M. Rosanoff-1906
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Rosanoff’s Wheel Rosanoff’s Reorganization of the Carbohydrates
Arranged by successive Kiliani syntheses The D- and L- assignments were Fischer’s based on chemical correlation with D-(+)-glucose, an unreliable scheme. 2 4 8 16 -series -series mirror plane
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Evolution of Signage Evolution of Signage Optical Activity
Configuration Fischer-1891 +/- d,l Rosanoff-1906 +/- Today +/- = d,l D,L
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D-Aldohexoses The D-Series of Aldoses aldotriose aldotetrose aldo
(+)-glyceraldehyde (+)-threose (-)-erythrose (-)-ribose (-)-arabinose (+)-xylose (-)-lyxose (+)-altrose (+)allose (+)-glucose (+)-mannose (-)-gulose (-)-idose (+)-galactose (+)-talose aldotriose aldotetrose aldo pentose aldo hexose All altruists gladly make gum in gallon tanks [L. Fieser]
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Fischer Projections Fischer Projections of Glucose CHO OH HO CH2OH CHO
3 4 5 CHO OH HOH2C HO = rotate C5 about C4 by 120o form hemiacetals between C5-OH and C1 D-(+)-Glucose
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Anomers Fischer Projections of Glucopyranose Anomers right alpha left
beta HO C C OH OH OH HO HO OH OH O O CH2OH CH2OH b-D-(+)-Glucopyranose a-D-(+)-Glucopyranose
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Haworth Haworth Projections of Glucopyranose Anomers up (top) beta
down (bottom) alpha b-D-(+)-Glucopyranose a-D-(+)-Glucopyranose
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Conformational Glucopyranose
Chair Conformations of Glucopyranose Anomers down (bottom) alpha up (top) beta O H O H b-D-(+)-Glucopyranose a-D-(+)-Glucopyranose
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How an Old Salt Remembers
starboard port right left green light red light fewer letters more letters alpha beta down up bottom top
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Mutarotation Mutarotation of Anomers a-D-(+)-Glucopyranose
H b-D-(+)-Glucopyranose O H Crystallizes above 98oC pure -anomer mp 150oC []D = +18.7o Crystallizes below 98oC pure -anomer mp 146oC []D = o H2O equilibrium mixture [] = +52.6o
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allose 92 8 altrose 70 30 glucose ~100(36.5/63.5) <1 mannose
Ring Sizes of Hexoses Ring Sizes of Hexoses Hexose Pyranose Form (%/%) Furanose Form allose 92 8 altrose 70 30 glucose ~100(36.5/63.5) <1 mannose ~100(67/33) gulose 97 3 idose 75 25 galactose 93(27.5/72.5) 7 talose 69 31 fructose 67 33
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Periodic acid Periodic Acid Cleavage of Carbohydrates as a Diagnostic Tool HIO4 OH 2 CH2=O OH HIO4 HIO4 CH2=O + OH CHO CH2=O HCO2H HIO4 OH HO H2O Formaldehyde (CH2O) arises from a primary alcohols Formic acid (HCO2H) arises from a secondary alcohols
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Periodic Acid Diagnostic
Periodic Acid Cleavage of Carbohydrates as a Diagnostic Tool OH HIO4 2 CH2=O HCO2H RCH2OH CH2=O R2CHOH HCO2H OH CHO HIO4 RCH=O HCO2H CH2=O HCO2H CO2 R2C=O HIO4 OH O CH2=O + OH CO2H HIO4 CH2=O CO2
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Periodic on Carbohydrates
Periodic Acid Cleavage of Carbohydrates CH2OH CHO HO OH D-glucose HCO2H HCO2H HCO2H HCO2H HCO2H H2CO HO OH CH2OH O D-fructose H2CO CO2 HCO2H HCO2H HCO2H CH2OH HO OH D-mannitol H2CO H2CO HCO2H HCO2H HCO2H HCO2H H2CO
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Methylation Methylation of Pyranosides HO OH O HO OH O OCH3 CH3OH, H+
CH3I Ag2O (CH3)2SO4 NaOH CH3O O OH OCH3 CH3O O OCH3 H3O+
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Ring Size Ring Size of Pyranosides OCH3 CO2H CH3O CH3O O OCH3 CO2H
HNO3 via oxidation of the enol of the ketone HNO3 HNO3 OCH3 CO2H CH3O CH3O O OH OCH3
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Periodic on Glycosides
Periodic Acid Cleavage of Methyl -Glucopyranoside OH O OCH3 OHC HCO2H HO OH O OCH3 HIO4 H3O+ OH CHO + OHCCHO CH3OH D-glyceraldehyde glyoxal
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Enzymes Enzymatic Cleavage of Glucosides H3O+ Methyl -D-glucoside
maltase -D-glucose emulsin -D-glucose
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Tollens + Ago The Silver Mirror Test Methyl -D-glucoside
Tollens reagent Ag(NH3)2+ OH- non-reducing sugar (a glycoside) no reaction + Ago silver mirror reducing sugar (an aldose) Tollens reagent Ag(NH3)2+ OH- D-glucose
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Tollens 2 Ago + The Silver Mirror Test enediol Ag(NH3)2+ OH-
-D-fructofuranose D-fructose Ag(NH3)2+ OH- enediol Ag(NH3)2+ OH- Ago + silver mirror Ag(NH3)2+ OH- Aldoses and ketoses are reducing sugars
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Intro: Di- and Polysaccharides
Disaccharides and Polysaccharides
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-D-Glucopyranosyl- -D-fructofuranoside
Sucrose/Olestra -D-Glucopyranosyl- -D-fructofuranoside or-D-Fructofuranosyl--D-glucopyranoside RCOO OOCR O Olestra (R=n-CnH2n+1; n=6-8) HO OH O Sucrose (non-reducing sugar) acetal ketal
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Sucrose is Formed from Glucose and Fructose
Woodward Sucrose is Formed from Glucose and Fructose This discussion brings to mind a wonderful story told to me by Professor Harry Wasserman (Yale), who during the late 1940's was a graduate student of Professor R. B. Woodward at Harvard. Apparently Woodward had received a notice of a $1,000 prize for the first person to accomplish a chemical synthesis of sucrose. He went into the laboratory and said to his students that all they had to do was connect two molecules of glucose together [...and lose a molecule of water] and they would have themselves $1,000. One student, obviously not overwhelmed by Woodward's stature in the field even at such a young age, replied that if you did it that way, the prize would be $2,000!
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Bees Do It Bees Do It CHO HO O OH CH2OH HO or H3O+
D-glucose []D = +52.7o dextrose Sucrose []D = +66.5o (non-reducing, non-mutarotating sugar) HO OH O or H3O+ invertase HO OH CH2OH O D-fructose []D = -92.4o levulose
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Disaccharides-Cellobiose
Cellulose (polysaccharide) 4-O-attachment -acetal linkage partial hydrolysis H3O+ emulsin,-glucosidase (termites, ruminants) Cellobiose (disaccharide) 4-O-(-D-glucopyranosyl)-D-glucopyranose
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Cellobiose-Structure Proof
Cellobiose-Str. Proof Cellobiose-Structure Proof Br2/H2O Cellobiose permethylation hydrolysis ----> only D-glucose emulsin ----> -glucoside positive Tollens test ----> reducing sugar tetramethoxy- carboxylic acid tetramethoxy aldehyde H3O+ shows mutarotation
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Cellobiose-Structure Proof
Cellobiose-Str. Proof Cellobiose-Structure Proof hot HNO3 dimethyl L-tartaric acid hot HNO3 tetramethoxy aldehyde tetramethoxy- carboxylic acid dimethyl D-glyceric acid trimethyl xylaric acid
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Disaccharides: Maltose
Starches: poly--D-glucosides Malt (barley) maltase hydrolysis ----> only D-glucose maltase ----> -glucoside positive Tollens test ----> reducing sugar shows mutarotation differs from cellobiose at the glycosidic anomeric center
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Disaccharides: Lactose
4-O-(-D-galactopyranosyl)-D-glucose ~5% of human and cow milk hydrolysis ----> D-glucose and D-galactose -galactosidase (lactase) ----> -galactoside positive Tollens test ----> reducing sugar lactose intolerance shows mutarotation
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Disaccharides: Amygdalin
Laetrile (laevorotatory mandelonitrile), “vitamin 17” 1,6--linkage cyanohydrin of benzaldehyde -linkage Isolated from bitter almonds by Wohler. Demonstrated that emulsin produces glucose, benzaldehyde and prussic acid (HCN) Touted in some circles as a treatment for cancer.
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Cellulose: Chain Length
permethylation H3O+ 2,3,4,6-tetra-O- methyl D-glucose (terminal) 2,3,6-tri-O- (chain) units 0.6% 99.4%
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Starches: Plant Polysaccharides
Amylose : ~20% water soluble starch; poly 4-O-(-D-glucoside) forms helical structure; blue complex with iodine
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Starches: Plant Polysaccharides
Amylopectin: ~80% water insoluble starch branched poly-4-O-(-D-glucoside) permethylation/hydrolysis permethylation: 95% 2,3,6-tri-O-methyl-D-glucose chain 2.5% 2,3-di-O-methyl-D-glucose junction 2.5% 2,3,4,6-tetra-O-methyl-D-glucose terminus Average 20 glucose units /chain
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Diogenes And Finally, a True Story
In March of 1986 I was in California visiting several universities. While at Stanford University, I stopped at the the health center to have a swollen foot examined. The young resident was very attentive. To assess his qualifications, I asked him where he had attended college. “M.I.T.,” he responded. “So you must have had Professor Kemp for organic chemistry,” I countered. “Yes, I did,” he said. Then I asked, “What D-aldohexose forms the same osazone as glucose?” Like Diogenes the Cynic in search of an honest man (person), I have posed this question to many a practitioner of the medical and dental professions. Neither Diogenes nor I have fulfilled our quests. However, the responses to my query were often amusing. Response: My thought: “I really enjoyed organic chemistry!” Really? “Organic, don’t remind me!” An honest man? “I know the mechanism of the aldol condensation.” Wrong chapter! “I know what a Grignard reagent is.” Wrong test! “Wait! Give me some time.” “It’s only an hour exam.”
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D-Mannose! Moral The Moral of the Story
Somewhere,…sometime…someone might ask you this question. What D-aldohexose forms the same osazone as D-glucose? Your answer will be... D-Mannose!
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The End The End
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