1. Dr. Wolf's CHM 424 25- 1 Modified Chapter 25 Carbohydrates

2. Dr. Wolf's CHM 424 25- 2 25.1 Classification of Carbohydrates

3. Dr. Wolf's CHM 424 25- 3 Classification of Carbohydrates monosaccharidedisaccharideoligosaccharidepolysaccharide

4. Dr. Wolf's CHM 424 25- 4 is not cleaved to a simpler carbohydrate on hydrolysis glucose, for example, is a monosaccharide MonosaccharideMonosaccharide

5. Dr. Wolf's CHM 424 25- 5 is cleaved to two monosaccharides on hydrolysis these two monosaccharides may be the same or different DisaccharideDisaccharide C 12 H 22 O 11 + H 2 O sucrose (a disaccharide) C 6 H 12 O 6 + C 6 H 12 O 6 glucose (a monosaccharide) fructose (a monosaccharide)

6. Dr. Wolf's CHM 424 25- 6 oligosaccharide: gives two or more monosaccharide units on hydrolysis is homogeneous—all molecules of a particular oligosaccharide are the same, including chain length gives two or more monosaccharide units on hydrolysis is homogeneous—all molecules of a particular oligosaccharide are the same, including chain length polysaccharide: yields "many" monosaccharide units on hydrolysis mixtures of the same polysaccharide differing only in chain length yields "many" monosaccharide units on hydrolysis mixtures of the same polysaccharide differing only in chain length Higher Saccharides

7. Dr. Wolf's CHM 424 25- 7 No. of carbonsAldoseKetose 4AldotetroseKetotetrose 4AldotetroseKetotetrose 5AldopentoseKetopentose 5AldopentoseKetopentose 6AldohexoseKetopentose 6AldohexoseKetopentose 7AldoheptoseKetoheptose 7AldoheptoseKetoheptose 8AldooctoseKetooctose 8AldooctoseKetooctose Table 25.1 Some Classes of Carbohydrates

8. Dr. Wolf's CHM 424 25- 8 25.2 Fischer Projections and D - L Notation

9. Dr. Wolf's CHM 424 25- 9 Fischer Projections

10. Dr. Wolf's CHM 424 25- 10 Fischer Projections

11. Dr. Wolf's CHM 424 25- 11 Fischer Projections of Enantiomers

12. Dr. Wolf's CHM 424 25- 12 Enantiomers of Glyceraldehyde CHO CH 2 OH HOH DCHO HHO L (+)-Glyceraldehyde(–)-Glyceraldehyde

13. Dr. Wolf's CHM 424 25- 13 25.3 The Aldotetroses

14. Dr. Wolf's CHM 424 25- 14 stereochemistry assigned on basis of whether configuration of highest-numbered stereogenic center is analogous to D or L -glyceraldehyde An Aldotetrose CHO CH 2 OH HOH HOH 1 2 3 4 D

15. Dr. Wolf's CHM 424 25- 15 An Aldotetrose CHO CH 2 OH HOH HOH 1 2 3 4 D -Erythrose

16. Dr. Wolf's CHM 424 25- 16 The Four Aldotetroses CHO CH 2 OH HOH HOH D -Erythrose L -Erythrose CHO CH 2 OH HO H H HO D -Erythrose and L -erythrose are enantiomers

17. Dr. Wolf's CHM 424 25- 17 The Four Aldotetroses CHO CH 2 OH HOH HOH CHO H HO HOH D -Erythrose D -Threose D -Erythrose and D -threose are diastereomers

18. Dr. Wolf's CHM 424 25- 18CHO CH 2 OH HO H H HO The Four Aldotetroses CHO CH 2 OH H HO HOH L -Erythrose D -Threose L -Erythrose and D -threose are diastereomers

19. Dr. Wolf's CHM 424 25- 19 The Four Aldotetroses CHO CH 2 OH H HO HOH D -Threose D -Threose and L -threose are enantiomers L -Threose OHCHO CH 2 OH H HO H

20. Dr. Wolf's CHM 424 25- 20 The Four Aldotetroses CHO CH 2 OH HOH HOHCHO H HO HOH H OHCHO H HO D -Erythrose L -Erythrose D -Threose L -Threose CHO CH 2 OH HO H H HO

21. Dr. Wolf's CHM 424 25- 21 25.4 Aldopentoses and Aldohexoses

22. Dr. Wolf's CHM 424 25- 22 The Aldopentoses There are 8 aldopentoses. Four belong to the D -series; four belong to the L -series. Their names are ribose, arabinose, xylose, and lyxose.

23. Dr. Wolf's CHM 424 25- 23 The Four D -Aldopentoses D -Ribose D -Arabinose D -Xylose D -Lyxose HOHHOHHOHHHO HOHHOHHOHHHO CH 2 OH H OH H OH H OH H OHCHO CHOCHO CHO

24. Dr. Wolf's CHM 424 25- 24 AldohexosesAldohexoses There are 16 aldopentoses. 8 belong to the D -series; 8 belong to the L - series. Their names and configurations are best remembered with the aid of the mnemonic described in Section 25.5.

25. Dr. Wolf's CHM 424 25- 25 25.5 A Mnemonic for Carbohydrate Configurations

26. Dr. Wolf's CHM 424 25- 26 The Eight D -Aldohexoses CHO CH 2 OH H OH

27. Dr. Wolf's CHM 424 25- 27 AllAltruistsGladlyMakeGumInGallonTanks The Eight D -Aldohexoses CHO CH 2 OH H OH

28. Dr. Wolf's CHM 424 25- 28 AllAllose AltruistsAltrose GladlyGlucose MakeMannose GumGulose InIdose GallonGalactose TanksTalose The Eight D -Aldohexoses CHO CH 2 OH H OH

29. Dr. Wolf's CHM 424 25- 29 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH

30. Dr. Wolf's CHM 424 25- 30 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH H OH

31. Dr. Wolf's CHM 424 25- 31 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH H HO

32. Dr. Wolf's CHM 424 25- 32 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH H OH

33. Dr. Wolf's CHM 424 25- 33 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH H OH H OH

34. Dr. Wolf's CHM 424 25- 34 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH H OH H HO

35. Dr. Wolf's CHM 424 25- 35 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH H HO

36. Dr. Wolf's CHM 424 25- 36 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH H HO H OH

37. Dr. Wolf's CHM 424 25- 37 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH H HO H HO

38. Dr. Wolf's CHM 424 25- 38 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH H OH H OH

39. Dr. Wolf's CHM 424 25- 39 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH H OH H OH H OH

40. Dr. Wolf's CHM 424 25- 40 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH H OH H OH H HO

41. Dr. Wolf's CHM 424 25- 41 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses HO CHO CH 2 OH H OH H OH H

42. Dr. Wolf's CHM 424 25- 42 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses HO CHO CH 2 OH H OH H OH H H OH

43. Dr. Wolf's CHM 424 25- 43 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses HO CHO CH 2 OH H OH H OH H H HO

44. Dr. Wolf's CHM 424 25- 44 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH H HO H OH

45. Dr. Wolf's CHM 424 25- 45 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH H HO H OH H OH

46. Dr. Wolf's CHM 424 25- 46 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH H HO H OH H HO

47. Dr. Wolf's CHM 424 25- 47 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH H HO H HO

48. Dr. Wolf's CHM 424 25- 48 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH H HO H HO H OH

49. Dr. Wolf's CHM 424 25- 49 AlloseAltroseGlucoseMannoseGuloseIdoseGalactoseTalose The Eight D -Aldohexoses CHO CH 2 OH H OH H HO H HO H HO

50. Dr. Wolf's CHM 424 25- 50 L -Aldohexoses There are 8 aldohexoses of the L -series. They have the same name as their mirror image except the prefix is L - rather than D -. CHO CH 2 OH H OH H OH H H OH HO D -(+)-Glucose L -(–)-Glucose CHO CH 2 OH H H H H OH HO HO HO

51. Dr. Wolf's CHM 424 25- 51 25.6 Cyclic Forms of Carbohydrates: Furanose Forms

52. Dr. Wolf's CHM 424 25- 52 Recall from Section 17.8 R"OH C O RR' R"O C O H RR' Product is a hemiacetal. +

53. Dr. Wolf's CHM 424 25- 53 Cyclic Hemiacetals Aldehydes and ketones that contain an OH group elsewhere in the molecule can undergo intramolecular hemiacetal formation. The equilibrium favors the cyclic hemiacetal if the ring is 5- or 6-membered. C OR OHOHOHOH C OH R O

54. Dr. Wolf's CHM 424 25- 54 equilibrium lies far to the right cyclic hemiacetals that have 5-membered rings are called furanose forms Carbohydrates Form Cyclic Hemiacetals CHO CH 2 OH 1 2 3 4 HOHO 1 23 4

55. Dr. Wolf's CHM 424 25- 55 stereochemistry is maintained during cyclic hemiacetal formation D -Erythrose CHO CH 2 OH 1 2 3 4 HOHO 1 23 4 H H OH OH H H H OHOH H

56. Dr. Wolf's CHM 424 25- 56 D -Erythrose turn 90° 1 2 3 4 1 2 3 4

57. Dr. Wolf's CHM 424 25- 57 D -Erythrose move O into position by rotating about bond between carbon-3 and carbon-4 1 2 3 4

58. Dr. Wolf's CHM 424 25- 58 D -Erythrose 1 2 3 4 1 2 3 4

59. Dr. Wolf's CHM 424 25- 59 D -Erythrose 1 2 3 4 close ring by hemiacetal formation between OH at C-4 and carbonyl group

60. Dr. Wolf's CHM 424 25- 60 D -Erythrose 1 2 3 4 1 2 3 4

61. Dr. Wolf's CHM 424 25- 61 stereochemistry is variable at anomeric carbon; two diastereomers are formed D -Erythrose CHO CH 2 OH 1 2 3 4 HOHO 1 23 4 H H OH OH H H H OHOH H anomeric carbon

62. Dr. Wolf's CHM 424 25- 62 D -Erythrose H OH O 1 23 4HH H OHOH H OH H O 1 23 4HH H OHOH H  - D -Erythrofuranose  - D -Erythrofuranose

63. Dr. Wolf's CHM 424 25- 63 D -Ribose CHO CH 2 OH H OHOHOHOH H OH H OH12 3 4 5 furanose ring formation involves OH group at C-4

64. Dr. Wolf's CHM 424 25- 64 D -Ribose CHO CH 2 OH H OHOHOHOH H OH H OH12 3 4 5 need C(3)-C(4) bond rotation to put OH in proper orientation to close 5-membered ring CHO H H H CH 2 OH OHOH HOHOHOHO 1 2 3 45

65. Dr. Wolf's CHM 424 25- 65 D -Ribose CHO H H H CH 2 OH OHOH HOHOHOHO 1 2 3 45 CHO H H H HOCH 2 OHOH OHOHOHOH 1 2 3 45

66. Dr. Wolf's CHM 424 25- 66 D -Ribose CH 2 OH group becomes a substituent on ring CHO H H H HOCH 2 OHOH OHOHOHOH 1 2 3 45 H OH O 1 23 4 H H OHOH H5  - D -Ribofuranose

67. Dr. Wolf's CHM 424 25- 67 25.7 Cyclic Forms of Carbohydrates: Pyranose Forms

68. Dr. Wolf's CHM 424 25- 68 cyclic hemiacetals that have 6-membered rings are called pyranose forms Carbohydrates Form Cyclic Hemiacetals H OH O 1 2 3 4 5 CHO CH 2 OH 12 3 4 5

69. Dr. Wolf's CHM 424 25- 69 D -Ribose CHO CH 2 OH 12 3 4 5 H H HOH OH OH CHO H H H OHOH HO 1 2 3 45 pyranose ring formation involves OH group at C-5

70. Dr. Wolf's CHM 424 25- 70 D -Ribose CHO H H H CH 2 OH OHOH HO 1 2 3 45 H OH O 1 2 3 4 OHOH HO H H H HH5  -D -Ribopyranose

71. Dr. Wolf's CHM 424 25- 71 D -Ribose H OH O 1 2 3 4 OHOH HO H H H HH5  -D -Ribopyranose OH H O 1 2 3 4 OHOH HO H H H HH5  -D -Ribopyranose

72. Dr. Wolf's CHM 424 25- 72 D -Glucose CHO CH 2 OH 12 3 4 5 H HO HOH H OH H OHOHOHOH 6 OHOHOHOH CHO H OH H OHH HO 1 2 3 4 56H pyranose ring formation involves OH group at C-5

73. Dr. Wolf's CHM 424 25- 73 D -Glucose CHO H OH H CH 2 OH OHH HO 1 2 3 4 56H OHOHOHOH CHO H OH H HOCH 2 OHH HO 1 2 3 4 56H OHOHOHOH need C(4)-C(5) bond rotation to put OH in proper orientation to close 6-membered ring

74. Dr. Wolf's CHM 424 25- 74 D -Glucose CHO H OH H HOCH 2 OHH HO 1 2 3 4 56H OHOHOHOH  -D -Glucopyranose H OH O 1 2 3 4 OHH HO H OH H H HOCH 2 56

75. Dr. Wolf's CHM 424 25- 75 D -Glucose  -D -Glucopyranose H OH O 1 2 3 4 OHH HO H OH H H HOCH 2 56  -D -Glucopyranose OH H O 1 2 3 4 OHH HO H OH H H HOCH 2 56

76. Dr. Wolf's CHM 424 25- 76 D -Glucose  -D -Glucopyranose H OH O 1 2 3 4 OHH HO H OH H H HOCH 2 56 pyranose forms of carbohydrates adopt chair conformations

77. Dr. Wolf's CHM 424 25- 77 D -Glucose  -D -Glucopyranose H OH O 1 2 3 4 OHH HO H OH H H HOCH 2 5 6 OH H OH H HO HOHH H O all substituents are equatorial in  - D -glucopyranose 1 2 3 4 5 6

78. Dr. Wolf's CHM 424 25- 78 D -Glucose  -D -Glucopyranose OH H OH H HO HOHH H HOCH 2 O OH group at anomeric carbon is axial in  - D -glucopyranose 1  -D -Glucopyranose H OH OH H HO HOHH H HOCH 2 O 1

79. Dr. Wolf's CHM 424 25- 79 Figure 25.5 CHO CH 2 OH H OHOHOHOH H OH H OH Less than 1% of the open-chain form of D -ribose is present at equilibrium in aqueous solution.

80. Dr. Wolf's CHM 424 25- 80 Figure 25.5 OH H OH H H HOHOH H O  -D -Ribopyranose (56%) H HO  -D -Ribopyranose (20%) H OH OH H HHOH H O 1 H 76% of the D -ribose is a mixture of the  and  - pyranose forms, with the  -form predominating

81. Dr. Wolf's CHM 424 25- 81 Figure 25.5 HOCH 2 H OH O H H OHOH H  - D -Ribofuranose (18%) HOCH 2 OH H O H H OHOH H  - D -Ribofuranose (6%) The  and  -furanose forms comprise 24% of the mixture.

82. Dr. Wolf's CHM 424 25- 82 25.8 Mutarotation

83. Dr. Wolf's CHM 424 25- 83 MutarotationMutarotation Mutarotation is a term given to the change in the observed optical rotation of a substance with time. Glucose, for example, can be obtained in either its  or  -pyranose form. The two forms have different physical properties such as melting point and optical rotation. When either form is dissolved in water, its initial rotation changes with time. Eventually both solutions have the same rotation.

84. Dr. Wolf's CHM 424 25- 84 Mutarotation of D -Glucose  -D -Glucopyranose OH H OH H HO HOHH H HOCH 2 O 1  -D -Glucopyranose H OH OH H HO HOHH H HOCH 2 O 1 Initial: [  ] D +18.7° Initial: [  ] D +112.2° Final: [  ] D +52.5°

85. Dr. Wolf's CHM 424 25- 85 Mutarotation of D -Glucose  -D -Glucopyranose OH H OH H HO HOHH H HOCH 2 O 1  -D -Glucopyranose H OH OH H HO HOHH H HOCH 2 O 1 Explanation: After being dissolved in water, the  and  forms slowly interconvert via the open- chain form. An equilibrium state is reached that contains 64%  and 36% .

86. Dr. Wolf's CHM 424 25- 86 25.9 Ketoses

87. Dr. Wolf's CHM 424 25- 87 KetosesKetoses Ketoses are carbohydrates that have a ketone carbonyl group in their open-chain form. C-2 is usually the carbonyl carbon.

88. Dr. Wolf's CHM 424 25- 88 ExamplesExamples D -Ribulose L -Xyulose D -Fructose HO H CH 2 OH O H OH H H O OH OHHO H O OH H H OH

89. Dr. Wolf's CHM 424 25- 89 25.13 Glycosides

90. Dr. Wolf's CHM 424 25- 90 GlycosidesGlycosides Glycosides have a substituent other than OH at the anomeric carbon. Usually the atom connected to the anomeric carbon is oxygen.

91. Dr. Wolf's CHM 424 25- 91 ExampleExample Linamarin is an O-glycoside derived from D -glucose. O OH OH HO HO HOCH 2 O OCC OH HO HO HOCH 2 CH 3 N D -Glucose

92. Dr. Wolf's CHM 424 25- 92 GlycosidesGlycosides Glycosides have a substituent other than OH at the anomeric carbon. Usually the atom connected to the anomeric carbon is oxygen. Examples of glycosides in which the atom connected to the anomeric carbon is something other than oxygen include S-glycosides and N- glycosides.

93. Dr. Wolf's CHM 424 25- 93 ExampleExample Adenosine is an N- glycoside derived from D -ribose HOCH 2 HOHO H H OHOH H D -Ribose HOCH 2 H N O H H OHOH H N NH 2 N N Adenosine

94. Dr. Wolf's CHM 424 25- 94 ExampleExample Sinigrin is an S-glycoside derived from D -glucose. O OH OH HO HO HOCH 2 D -Glucose O SCCH 2 CH OH HO HO HOCH 2 CH 2 NOSO 3 K

95. Dr. Wolf's CHM 424 25- 95 GlycosidesGlycosides O-Glycosides are mixed acetals.

96. Dr. Wolf's CHM 424 25- 96 O-Glycosides are mixed acetals H OH O CHO CH 2 OH hemiacetal H OR O ROH acetal

97. Dr. Wolf's CHM 424 25- 97 Preparation of Glycosides Glycosides of simple alcohols (such as methanol) are prepared by adding an acid catalyst (usually gaseous HCl) to a solution of a carbohydrate in the appropriate alcohol. Only the anomeric OH group is replaced. An equilibrium is established between the  and  -glycosides (thermodynamic control). The more stable stereoisomer predominates.

98. Dr. Wolf's CHM 424 25- 98 Preparation of Glycosides HO CHO CH 2 OH H OH H OH H H OH CH 3 OH HCl D -Glucose O OCH 3 OH HO HO HOCH 2 + O OCH 3 OH HO HO HOCH 2

99. Dr. Wolf's CHM 424 25- 99 Preparation of Glycosides O OCH 3 OH HO HO HOCH 2 + O OCH 3 OH HO HO HOCH 2 Methyl  - D -glucopyranoside Methyl  - D -glucopyranoside (major product)

100. Dr. Wolf's CHM 424 25- 100 Mechanism of Glycoside Formation HCl carbocation is stabilized by lone-pair donation from oxygen of the ring O OH OH HO HO HOCH 2 O OH HO HO HOCH 2 + H

101. Dr. Wolf's CHM 424 25- 101 Mechanism of Glycoside Formation O OH HO HO HOCH 2 + H O H CH 3 O O OH HO HO HOCH 2 CH 3 H + + O OH HO HO HOCH 2 O H H3CH3CH3CH3C +

102. Dr. Wolf's CHM 424 25- 102 Mechanism of Glycoside Formation O O OH HO HO HOCH 2 CH 3 H + + O OH HO HO HOCH 2 O H H3CH3CH3CH3C + + O OCH 3 OH HO HO HOCH 2 –H+ O OCH 3 OH HO HO HOCH 2

103. Dr. Wolf's CHM 424 25- 103 25.14 Disaccharides

104. Dr. Wolf's CHM 424 25- 104 DisaccharidesDisaccharides Disaccharides are glycosides. The glycosidic linkage connects two monosaccharides. Two structurally related disaccharides are cellobiose and maltose. Both are derived from glucose.

105. Dr. Wolf's CHM 424 25- 105 Maltose and Cellobiose Maltose Maltose is composed of two glucose units linked together by a glycosidic bond between C-1 of one glucose and C-4 of the other. The stereochemistry at the anomeric carbon of the glycosidic linkage is . The glycosidic linkage is described as  (1,4) O HOCH 2 OH OH HO OH HO HO O O 14 

106. Dr. Wolf's CHM 424 25- 106 Maltose and Cellobiose Cellobiose Cellobiose is a stereoisomer of maltose. The only difference between the two is that cellobiose has a  (1,4) glycosidic bond while that of maltose is  (1,4). O HOCH 2 OH OH HO OH HO HO O O 14 

107. Dr. Wolf's CHM 424 25- 107 Maltose and Cellobiose CellobioseMaltose

108. Dr. Wolf's CHM 424 25- 108 Cellobiose and Lactose Cellobiose Cellobiose and lactose are stereoisomeric disaccharides. Both have  (1,4) glycosidic bonds. The glycosidic bond unites two glucose units in cellobiose. It unites galactose and glucose in lactose. O HOCH 2 OH OH HO OH HO HO O O 14 

109. Dr. Wolf's CHM 424 25- 109 Cellobiose and Lactose Lactose Cellobiose and lactose are stereoisomeric disaccharides. Both have  (1,4) glycosidic bonds. The glycosidic bond unites two glucose units in cellobiose. It unites galactose and glucose in lactose. O HOCH 2 OH OH HO OH HO HO O O 14 

110. Dr. Wolf's CHM 424 25- 110 25.18 Reduction of Carbohydrates

111. Dr. Wolf's CHM 424 25- 111 Reduction of Carbohydrates Carbonyl group of open-chain form is reduced to an alcohol. Product is called an alditol. Alditol lacks a carbonyl group so cannot cyclize to a hemiacetal.

112. Dr. Wolf's CHM 424 25- 112 Reduction of D -Galactose  - D -galactofuranose  - D -galactofuranose  - D -galactopyranose  - D -galactopyranose CH 2 OH H OH H HO H HO H OHCHO H OH H HO H HO H OH D -Galactitol (90%) reducing agent: NaBH 4, H 2 O (catalytic hydrogenation can also be used)

113. Dr. Wolf's CHM 424 25- 113 25.19 Oxidation of Carbohydrates

114. Dr. Wolf's CHM 424 25- 114 Benedict's Reagent Benedict's reagent is a solution of the citrate complex of CuSO 4 in water. It is used as a test for "reducing sugars." Cu 2+ is a weak oxidizing agent. A reducing sugar is one which has an aldehyde function, or is in equilibrium with one that does. A positive test is the formation of a red precipitate of Cu 2 O. + 2Cu 2+ RCHO 5HO – + + Cu 2 O RCO – O 3H 2 O +

115. Dr. Wolf's CHM 424 25- 115 Examples of Reducing Sugars Aldoses: because they have an aldehyde function in their open-chain form. Ketoses: because enolization establishes an equilibrium with an aldose. CH 2 OH C O RCHOHC OH R CH CHOH RO oxidized by Cu 2+

116. Dr. Wolf's CHM 424 25- 116 Examples of Reducing Sugars Disaccharides that have a free hemiacetal function. O HOCH 2 OH OH HO OH HO HO O O Maltose

117. Dr. Wolf's CHM 424 25- 117 Examples of Reducing Sugars Disaccharides that have a free hemiacetal function. oxidized by Cu 2+ O HOCH 2 OH HO OH HO HO OOH CH O Maltose

118. Dr. Wolf's CHM 424 25- 118 Glycosides are not reducing sugars O OCH 3 OH HO HO HOCH 2 Methyl  - D -glucopyranoside lacks a free hemiacetal function; cannot be in equilibrium with a species having an aldehyde function

119. Dr. Wolf's CHM 424 25- 119 Oxidation of Reducing Sugars The compounds formed on oxidation of reducing sugars are called aldonic acids. Aldonic acids exist as lactones when 5- or 6- membered rings can form. A standard method for preparing aldonic acids uses Br 2 as the oxidizing agent.

120. Dr. Wolf's CHM 424 25- 120 Oxidation of D -Xylose HO H OH H OH HCHO CH 2 OH Br 2 H2OH2OH2OH2O D -Xylose HO H OH H OH H CH 2 OH CO 2 H D -Xylonic acid (90%)

121. Dr. Wolf's CHM 424 25- 121 Oxidation of D -Xylose HO H OHOHOHOH H OH H CH 2 OH CO 2 H D -Xylonic acid (90%) O O OH OH HOCH 2 OOOH HO HOHOHOHO +

122. Dr. Wolf's CHM 424 25- 122 Ruff Degradation Part 1,Oxidation of D -Glucose CHO CH 2 OH H OH H OH H H OH HO H OH H OH H H OH HO CO 2 H D -Gluconic acid D -Glucose Br 2 H2OH2OH2OH2O

123. Dr. Wolf's CHM 424 25- 123 Ruff Degradation Part 2,Oxidized Carbon Removed CH 2 OH H OH H OH H H OH HO CO 2 H D -Gluconic acid 1) CaCO 3 2) H 2 O 2, Fe +3 H H OH H OHCHO CH 2 OH HO D -Arabinose

124. Dr. Wolf's CHM 424 25- 124 Nitric Acid Oxidation Nitric acid oxidizes both the aldehyde function and the terminal CH 2 OH of an aldose to CO 2 H. The products of such oxidations are called aldaric acids.

125. Dr. Wolf's CHM 424 25- 125 Nitric Acid Oxidation CHO CH 2 OH H OH H OH H H OH HO HNO 3 60°C CO 2 H H OH H OH H H OH HO D -Glucaric acid (41%) D -Glucose

126. Dr. Wolf's CHM 424 25- 126 25.20 Cyanohydrin Formation and Carbohydrate Chain Extension Kiliani-Fischer Synthesis

127. Dr. Wolf's CHM 424 25- 127 Extending the Carbohydrate Chain Carbohydrate chains can be extended by using cyanohydrin formation as the key step in C—C bond-making. The classical version of this method is called the Kiliani-Fischer synthesis. The following example is a more modern modification.

128. Dr. Wolf's CHM 424 25- 128  - L -arabinofuranose  - L -arabinofuranose  - L -arabinopyranose  - L -arabinopyranose CH 2 OH H HO H HO H OHCHO Extending the Carbohydrate Chain HCN CH 2 OH HO H H HO OH HCN CHOH the cyanohydrin is a mixture of two stereoisomers that differ in configuration at C-2; these two diastereomers are separated in the next step

129. Dr. Wolf's CHM 424 25- 129 Extending the Carbohydrate Chain CH 2 OH HO H H HO OH HCN CHOH CH 2 OH HO H H HO OH H H OHOHOHOHCN HO H H HO OH H HOHOHOHO HCN+ separate L -Mannononitrile L -Gluconononitrile

130. Dr. Wolf's CHM 424 25- 130 Extending the Carbohydrate Chain CH 2 OH HO H H HO OH H H OHOHOHOHCN L -Mannononitrile H 2, H 2 O Pd, BaSO 4 L -Mannose (56% from L -arabinose) CH 2 OH HO H H HO OH H H OHOHOHOH CHCHCHCHO

131. Dr. Wolf's CHM 424 25- 131 Likewise...Likewise... CH 2 OH HO H H HO OH H HOHOHOHO HCN L -Gluconononitrile H 2, H 2 O Pd, BaSO 4 L -Glucose (26% from L -arabinose) CH 2 OH HO H H HO OH H HOHOHOHO H CHCHCHCHO

132. Dr. Wolf's CHM 424 25- 132 25.21 Epimerization and Isomerization of Carbohydrates

133. Dr. Wolf's CHM 424 25- 133 Enol Forms of Carbohydrates Enolization of an aldose scrambles the stereochemistry at C-2. This process is called epimerization. Diastereomers that differ in stereochemistry at only one of their stereogenic centers are called epimers. D -Glucose and D -mannose, for example, are epimers.

134. Dr. Wolf's CHM 424 25- 134 EpimerizationEpimerization CHO CH 2 OH H OH H OH H H OH HO D -Mannose D -Glucose CHO CH 2 OH H OH H OH H HO H HO Enediol H OH H OH H OH HOCHOHC This equilibration can be catalyzed by hydroxide ion.

135. Dr. Wolf's CHM 424 25- 135 Enol Forms of Carbohydrates The enediol intermediate on the preceding slide can undergo a second reaction. It can lead to the conversion of D -glucose or D -mannose (aldoses) to D -fructose (ketose).

136. Dr. Wolf's CHM 424 25- 136 IsomerizationIsomerization Enediol CH 2 OH H OH H OH H OH HOCHOHC D -Glucose or D -Mannose CHO CH 2 OH H OH H OH H HO CHOH D -Fructose CH 2 OH H OH H OH H HO CO

137. Dr. Wolf's CHM 424 25- 137 25.22 Acylation and Alkylation of Hydroxyl Groups in Carbohydrates

138. Dr. Wolf's CHM 424 25- 138 Reactivity of Hydroxyl Groups in Carbohydrates acylation alkylation Hydroxyl groups in carbohydrates undergo reactions typical of alcohols.

139. Dr. Wolf's CHM 424 25- 139 Example: Acylation of  - D -glucopyranose O OH OH HO HO HOCH 2 + CH 3 COCCH 3 OO 5 pyridine O O CH 3 COCH 2 O CH 3 CO O O O OCCH 3 (88%)

140. Dr. Wolf's CHM 424 25- 140 Example: Alkylation of methyl  - D -glucopyranoside O OCH 3 OH HO HO HOCH 2 + 4CH 3 I Ag 2 O, CH 3 OH O OCH 3 CH 3 O CH 3 OCH 2 (97%)

141. Dr. Wolf's CHM 424 25- 141 Classical Method for Ring Size Ring sizes (furanose or pyranose) have been determined using alkylation as a key step. O OCH 3 OH HO HO HOCH 2 OCH 3 O CH 3 O CH 3 OCH 2

142. Dr. Wolf's CHM 424 25- 142 Classical Method for Ring Size Ring sizes (furanose or pyranose) have been determined using alkylation as a key step. O OCH 3 CH 3 O CH 3 OCH 2 H2OH2OH2OH2O H+H+H+H+ (mixture of  +  ) O OH CH 3 O CH 3 OCH 2

143. Dr. Wolf's CHM 424 25- 143 Classical Method for Ring Size Ring sizes (furanose or pyranose) have been determined using alkylation as a key step. (mixture of  +  ) O OH CH 3 O CH 3 OCH 2 CH 2 OCH 3 H OHOHOHOH OCH 3 H H CH 3 O H OCH 3 CHO

144. Dr. Wolf's CHM 424 25- 144 Classical Method for Ring Size Ring sizes (furanose or pyranose) have been determined using alkylation as a key step. CH 2 OCH 3 H OHOHOHOH OCH 3 H H CH 3 O H OCH 3 CHO This carbon has OH instead of OCH 3. Therefore,its O was the oxygen in the ring.

145. Dr. Wolf's CHM 424 25- 145 End of Chapter 25