Organic Chemistry III

Transcription

1 rganic Chemistry III (Yuki Goto, Bioorganic Chemistry Lab.) rganic chemistry of biomolecules rganic chemistry of radicals 6/6 (Wed) 6/13 (Wed) 6/20 (Wed) 6/27 (Wed) 7/4 (Wed)

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3 Examples of biomolecules?

4 Today s topic is carbohydrates also called sugars or saccharides Examples of carbohydrates serve as energy storage general formula: Cn2mm contain many functional groups and chiral centers

5 Classification of carbohydrates monosaccharide ( ) disaccharide ( ) trisaccharide ( ),... polysaccharide ( )

6 Topics structure of monosaccharide - classification - Fischer projection - cyclic sugars reactions of monosaccharide - several examples of monosaccharides - glycoside formation (glycosylation) - protection strategies of monosaccharides structure and functions of oligo and polysaccharide

7 Classification of monosaccharide monosaccharide aldose aldotriose (C3) aldotetrose (C4) aldopentose (C5) aldohexose (C6) ketose pentose ( ), hexose ( ) ketotriose (C3) ketotetrose (C4) ketopentose (C5) ketohexose (C6)

8 Classification of monosaccharide Quiz-1: Classify the following monosaccharides

9 ow to draw structures of sugars Fischer projection Fischer This looks like a planar structural formula but indeed indicates the following stereochemistry. Press and project the structure onto the bottom paper bonds sticking out from paper bonds sticking into backward

10 Tips for Fischer projection drawing 1. (In the cases of saccharides,) put the aldehyde/ketone group above. And, align the carbon chain vertically. Carbons are numbered starting with the top carbon. 2. In the projection of each carbon, make the adjacent carbons land first. 3. You can rotate a Fischer projection 180. (You must not rotate it 90 ) 4. You can fix one substitution and rotate the remaining three groups.

11 Tips for Fischer projection drawing Let s use a simple aldotriose, (R)-glyceraldehyde, as a model case. bonds sticking out from paper bonds sticking into backward 1. (In the cases of saccharides,) put the aldehyde/ketone group above. And, align the carbon chain vertically. Carbons are numbered starting with the top carbon. 2. In the projection of each carbon, make the adjacent carbons land first. puzzling,

12 Tips for Fischer projection drawing 3. You can rotate a Fischer projection 180. (You must not rotate it 90 ) (R)-glyceraldehyde (R)-glyceraldehyde (R)-glyceraldehyde (S)-glyceraldehyde 4. You can fix one substitution and rotate the remaining three groups. fix this group

13 Fischer projection drawing Quiz-2: Draw the Fischer projection of the sugar below. Quiz-3: Designate the stereogenic carbon of the following compounds as either (R) or (S). (a) (b)

14 Fischer projection drawing Quiz-4: Use solid-wedge and dashed-wedge notation to write 3D representation for the following molecule shown in Fischer projection.

15 D/L nomenclature In organic chemistry, we generally use R/S nomenclature to designate stereochemistry. In biochemistry and even organic chemistry of biomolecules, we also use D/L nomenclature! mirror L-glucose (very rare in nature) D-glucose

16 ow complicated sugars are! ere, only D-sugars are shown. Imagine there are also enantiomers of these sugars as L-sugars. D-aldotriose D-aldotetrose D-aldopentose

17 ow complicated sugars are! ere, only D-sugars are shown. Imagine there are also enantiomers of these sugars as L-sugars. D-aldopentose D-aldohexose

18 Fischer projections are not real form of the sugars D-glucose Review quiz: + R R

19 Fischer projections are not real form of the sugars D-glucose Review quiz: + R R R R R R R hemiacetal acetal in sugar chemistry, cyclic form glycoside

20 Formation of cyclic sugars via hemiacetal formation furan pyran

21 Formation of cyclic sugars via hemiacetal formation e.g. D-glucose s case new chiral center! Squiggle indicates both stereoisomers are present (mixed)

22 Formation of cyclic sugars via hemiacetal formation new chiral center! anomeric position * = 37 α-d-glucopyranose * anomers * Squiggle indicates both stereoisomers are present (mixed) D-glucopyranose β-d-glucopyranose = * 63 If the on the new chiral center is located on the same side with the on the D/L determining carbon in Fischer projection, it is α-anomer. Review quiz: Identify the new stereogenic carbon in the α and β anomers as either (R) or (S).

23 Formation of cyclic sugars via hemiacetal formation Quiz-5: ere is the Fischer projection of D-mannose. Draw the structure of β-d-mannopyranose in chair structure. D-mannose

24 Topics structure of monosaccharide - classification - Fischer projection - cyclic sugars reactions of monosaccharide - several examples of monosaccharides - glycoside formation (glycosylation) - protection strategies of monosaccharides structure and functions of oligo and polysaccharide

25 Reaction of monosaccharides - 1 Simple transformation of functional groups functional groups in sugars possible reactions aldehydes reduction to alcohol oxidation to carboxyl group alcohols alkylation to ethers acylation to esters Review quiz: Give an example(s) of reagents/conditions to achieve each transformation.

26 Reaction of monosaccharides - 1 Simple transformation of functional groups e.g. reduction of the terminal aldehyde to alcohol No aldehyde!

27 Reaction of monosaccharides - 1 Simple transformation of functional groups e.g. alkylation of hydroxy groups Williamson ether synthesis

28 Reaction of monosaccharides - 1 Simple transformation of functional groups e.g. acylation of hydroxy groups

29 Reaction of monosaccharides - 2 Truncation of chains in monosaccharides (Ruff degradation) racemic (oxidation) -C 2, retention of configuration Note; Br2 acts as a mild oxidant. Whereas the aldehyde is oxidized, hydroxy groups are intact.

30 Reaction of monosaccharides - 3 Elongation of chains in monosaccharides (Kiliani-Fischer synthesis) cyanohydrin imine partial hydrogenation hydrolysis Review quiz: Draw the mechanism of the hydrolysis of the imine under acidic conditions.

31 Reaction of monosaccharides - 4 Epimerization under basic conditions (Lobry de Bruijn-Alberda van Ekenstein reaction) D-glucose can be slowly converted to D-mannose and D-fructose under basic conditions! ketose! epimerized at C2 W!? Quiz-6: Although D-fructose (open chain form) is here shown to emphasize it is a ketose, it actually exists in the pyranose and furanose form. Draw Fischer projections for the pyranose and furanose forms of D-fructose.

32 Reaction of monosaccharides - 4 Epimerization under basic conditions (Lobry de Bruijn-Alberda van Ekenstein reaction) D-glucose can be slowly converted to D-mannose and D-fructose under basic conditions! ketose! pyranose form furanose form Quiz-6: Although D-fructose (open chain form) is shown here to emphasize it is a ketose, it actually exists in the pyranose and furanose form. Draw Fischer projections for the pyranose and furanose forms of D-fructose.

33 Reaction of monosaccharides - 4 Epimerization under basic conditions (Lobry de Bruijn-Alberda van Ekenstein reaction) ketose! epimerized at C2

34 Reaction of monosaccharides - 4 Epimerization under basic conditions (Lobry de Bruijn-Alberda van Ekenstein reaction) ketose! epimerized at C2 protonation on oxygen

35 Reaction of monosaccharides - 5 Synthesis of glycosides If glucose is reacted with alcohols, what can occur? Remind this R R + R R R R R hemiacetal acetal in sugar chemistry, cyclic form glycoside

36 Synthesis of glycosides Reaction of monosaccharides - 5 If glucose is reacted with alcohols, what can occur? acetal glycosides: (in a narrow sense,) acetal forms of sugars on the anomeric position nomenclature - giving the alkyl group followed by the sugar name with the -ose replaced with -oside e.g. the name of the glycoside above is methyl D-glucopyranoside Review quiz: Draw the mechanism of the glycoside formation under acidic conditions.

37 Selective protection of monosaccharides D-glucopyranose ow? Me Me Me Me Review quiz: Draw the mechanism of the last reaction.

38 Selective protection of monosaccharides acetonide - protective group of 1,2- and 1,3- diols R R R R Ac acetone, + toluene Ac Ac acetone, + toluene Ac nly syn 1,2-diols can be protected by acetonide. Review practice: Draw the mechanism of protection and deprotection of acetonide group.

39 Stereoselective glycosylation Br R Ag 2 R β-anomer selective

40 Stereoselective glycosylation Br R Ag 2 R β-anomer selective Ac Ac Ac Ac Ac Ac Br

41 If R in glycosylation is a sugar disaccharides Dimers of D-glucopyranose α-d-glucopyranose α-d-glucopyranoside β-d-glucopyranoside α(1 4) glycosidic bond (maltose) lactose 乳糖 β-d-glucopyranose β-d-glucopyranose β(1 4) glycosidic bond (cellobiose) sucrose ショ糖 砂糖 α-d-glucopyranoside α-d-fructofuranoside β-d-galactopyranoside β(1 4) glycosidic bond α(1 2) glycosidic bond

42 If R in glycosylation is a sugar disaccharides Dimers of D-glucopyranose α-d-glucopyranose α-d-glucopyranoside β-d-glucopyranoside α(1 4) glycosidic bond (maltose) lactose 乳糖 β-d-glucopyranose β-d-glucopyranose β(1 4) glycosidic bond (cellobiose) sucrose ショ糖 砂糖 α-d-glucopyranoside α-d-fructofuranoside β-d-galactopyranoside β(1 4) glycosidic bond α(1 2) glycosidic bond

43 Two important polysaccharides Both are polymers of D-glucopyranose see 3D structures amylose デンプンの構成要素 α(1 4) glycosidic bond helical structure of amylose (good energy source) cellulose β(1 4) glycosidic bond planar structure of cellulose (we cannot digest this)

44 topics- roles of polysaccharides in organisms energy storage - amylose, glycogen, etc. structural skeleton - cellulose, chitin, etc. regulation of cellular events Many different polysaccharide chains are found on exterior surface of cells. Different cells display different poly saccharine chain on the surface. They play important roles in - definition/recognition of cellular types - infection of viruses - regulation of growth factors additional N-acetylgalactosamine additional galactose red blood cell red blood cell red blood cell red blood cell type A type B type AB type

45 Classification of monosaccharide Quiz-1: Classify the following monosaccharides aldotetrose ketopentose ketohexose aldopentose

46 Fischer projection drawing Quiz-2: Draw the Fischer projection of the sugar below. Quiz-3: Designate the stereogenic carbon of the following compounds as either (R) or (S). (a) (b)

47 Fischer projection drawing Quiz-2: Draw the Fischer projection of the sugar below. C C 2

48 Fischer projection drawing Quiz-3: Designate the stereogenic carbon of the following compounds as either (R) or (S). (a) (b) = 4 (S) 3 C C = 3 C 1 C 2 3 C (R)

49 Fischer projection drawing Quiz-4: Use solid-wedge and dashed-wedge notation to write 3D representation for the following molecule shown in Fischer projection. = C = C 2

50 Formation of cyclic sugars via hemiacetal formation new chiral center! anomeric position * = 37 α-d-glucopyranose * anomers * Squiggle indicates both stereoisomers are present (mixed) D-glucopyranose β-d-glucopyranose = * 63 If the on the new chiral center is located on the same side with the on the D/L determining carbon in Fischer projection, it is α-anomer. Review quiz: Identify the new stereogenic carbon in the α and β anomers as either (R) or (S). (S) (R)

51 Formation of cyclic sugars via hemiacetal formation Quiz-5: ere is the Fischer projection of D-mannose. Draw the structure of β-d-mannopyranose in chair structure. D-mannose = C C 2 = = C 2

52 Formation of cyclic sugars via hemiacetal formation Quiz-5: ere is the Fischer projection of D-mannose. Draw the structure of β-d-mannopyranose in chair structure. C 2 C 2 =

53 Formation of cyclic sugars via hemiacetal formation Quiz-5: ere is the Fischer projection of D-mannose. Draw the structure of β-d-mannopyranose in chair structure. an alternative process to think C 2 = = C 2

54 Reaction of monosaccharides - 4 Epimerization under basic conditions (Lobry de Bruijn-Alberda van Ekenstein reaction) D-glucose can be slowly converted to D-mannose and D-fructose under basic conditions! ketose! C 2 C 2 2 C pyranose form C 2 furanose form Quiz-6: Although D-fructose (open chain form) is shown here to emphasize it is a ketose, it actually exists in the pyranose and furanose form. Draw Fischer projections for the pyranose and furanose forms of D-fructose.