II. OCCURRENCE, PROPERTIES, AND SYNTHESIS OF THE MONOSACCHARIDES
JOHN C. SOWDEN
1. NATURALLY OCCURRING MONOSACCHARIDES
A. INTRODUCTION
Many sugars and deoxysugars are found free or combined in naturally occurring materials. These sugars are of particular importance because of the interest in their biological function and in their present or potential industrial application. To the sugar chemist, these sugars are of value in providing, along with the natural sugar alcohols and uronic acids, starting materials for the preparation of the synthetic sugars. The list of known naturally occurring sugars and deoxysugars gradually is being expanded as isolation procedures are developed and improved. The biosynthesis of many is discussed in Chapter XIII and their nutritional aspects in Chapter XIV.
D-Glucose, free or combined, undoubtedly is the most widely distributed of the sugars. Other aldohexoses found in natural products are D-mannose and D- and L-galactose. D-Fructose is the only abundant natural ketose.
The occurrence of another hexulose, D-tagatose, has been established (./), but the reported isolation (2) of L-sorbose needs further substantiation.
Of the pentoses, D-xylose, D-ribose, and D- and L-arabinose are of biological origin. L-ZAreo-Pentulose (L-xylulose) is excreted in the urine of patients with pentosuria and D-en/J/iro-pentulose (D-ribulose) has been recognized as an intermediate in carbohydrate metabolism and photosynthesis. Both of these ketopentoses have been reported to occur in minor amounts in normal human urine. The aldotetrose ester, D-erythrose 4-phosphate, is an intermediate in several natural enzymic transformations. The three-carbon sugar series is represented by glyceraldehyde and dihydroxyacetone, which occur as their phosphate derivatives in the intermediate stages of cellular metabolism as well as in many other related biological processes. Two heptuloses, two aldoheptoses (2a) and two heptitols have been isolated from natural products.
1. E. L. Hirst, L. Hough, and J. K. N. Jones, Nature 163, 177 (1949).
2. C. M. Martin and F. H. Reuter, Nature 164, 407 (1949).
2a. M. W. Slein and G. W. Schnell, Proc. Soc. Exptl. Biol. Med. 82, 734 (1953);
W. Weidel, Z. physiol. Chem. 299, 253 (1955); A. P. Maclennan and D. A. L.
Davies, Biochem. J. 63, 31p (1956).
77
78 JOHN C. SOWDEN
Sedoheptulose occurs as an intermediate in photosynthesis and carbo- hydrate metabolism (Chapter XIII).
The presence in plant materials of L-glucose, the enantiomorph of the ubiquitous D-glucose, has been reported (8) but needs confirmation. How- ever, the natural occurrence of 2-deoxy-2-iV-methylamino-L-glucose in streptomycin and of 6-deoxy-3-0-methyl-L-glucose (L-thevetose) in certain cardiac glycosides has been established.
Many deoxysugars, formally derived from ordinary sugars by the re- placement of a hydroxyl group by a hydrogen atom, are of biological origin.
The sugars with a terminal methyl rather than a primary alcohol group are the most common deoxysugars. All of the aldohexoses mentioned above are represented in the D- or L-form by naturally occurring 6-deoxy-D- glucose, 6-deoxy-D- and -L-galactose (D- and L-fucose), and 6-deoxy-L- mannose (L-rhamnose). 2-Deoxy-D-en/#&r0-pentose (2-deoxy-D-ribose) is widely distributed in cellular materials as the sugar component of the deoxynucleic acids. A large variety of 6-deoxy- and 2,6-dideoxy-aldohexoses and their 3-0-methyl ethers are found as constituents of the cardiac glyco- sides (Chapter X).
Sugars and deoxysugars with branched carbon chains also occur in na- ture (Chapter X). These include apiose (4) and hamamelose (5), found in plant sources, and streptose (6), cordycepose (7), mycarose (&), and cladi- nose (8a), which occur as constituents of antibiotic substances.
The natural sugars may exist free, or combined as components of larger molecules such as oligosaccharides, polysaccharides, glycosides, etc. The better-defined polysaccharides are usually homopolymers of monosac- charides: cellulose, starch, and glycogen are D-glucose polymers; inulin gives D-fructose; and pectins yield mainly D-galacturonic acid on hydrolysis.
Other polysaccharides (gums, hemicelluloses, and many animal polysac- charides) are heteropolymers of simple sugars, uronic acids, and amino sugars (Chapter XII).
8. F. B. Power and F. Tutin, Chem. Zentr. 77, Part II, 1623 (1906); H. Saha and and K. N. Choudhury, J. Chem. Soc. 121, 1044 (1922).
4- See C. S. Hudson, Advances in Carbohydrate Chem. 4, 57 (1949).
5. See O. T. Schmidt, Ann. 476, 250 (1929); O. T. Schmidt and K. Heintz, ibid.
515,77 (1934).
6. F. A. Kuehl, Jr., M. N. Bishop, E. H. Flynn, and K. Folkers, J. Am. Chem. Soc.
70, 2613 (1948); M. L. Wolfrom and C. W. DeWalt, ibid. 70, 3148 (1948).
7. K. G. Cunningham, S. A. Hutchinson, W. Manson, and F. S. Spring, J. Chem.
Soc. p. 2299 (1951) ; H. R. Bentley, K. G. Cunningham, and F. S. Spring, ibid. p. 2301 (1951).
8. P. P. Regna, F. A. Hochstein, R. L. Wagner, Jr., and R. B. Woodward, J. Am.
Chem. Soc. 75, 4625 (1953).
8a. P. F. Wiley and O. Weaver, J. Am. Chem. Soc. 77, 3422 (1955); 78, 808 (1956).
II. MONOSACCHARIDES: OCCURRENCE, PROPERTIES, SYNTHESIS CHO
CH2OH /
c
| \
CHO OH HCOH HCOH
79
COH
HOH2C CH/ \ 2OH Apiose
HCOH CH20H
I
Hamamelose
CHO
I
HCOH
I
OHCCOH
I
HOCH CH3 Streptose
CHO CHOH
I
CH
I
HOH2C CH2OH / \ Cordycepose
CHO
I
CH2
CH3
/ C
\ OH
CHOH CHOH CH3
I
Mycarose
CHO
I
CH2
CH3
/ C
\ OCH3
CHOH CHOH CH3
I
Cladinose B. ORIGIN AND PREPARATION OF SOME NATURALLY
OCCURRING MONOSACCHARIDES a. Pentoses
L-Arabinose
OH OH H I I I (HO)HoC- C—C— C - CHO 2
I I I H H OH
H OH 0-L-Arabopyranose aldehydo-ii-Arabmose
Occurrence. The sugar occurs in the free state in the heartwood of many coniferous trees. In a combined state, it is very widely distributed in plant
PHYSICAL PROPERTIES AND DERIVATIVES OF SOME NATURAL MONOSACCHARIDES" oo o
Sugar
Aldopentose L-Arabinosec D-Ribose D-Xylose
Ketopentose D-eryiAro-Pentulose
(D-Ribulose)
L-iÄreo-Pentulose (L-Xylulose) Deoxypentose
2-Deoxy-D-er2//Aro-pentose (2-Deoxy-D-ribose) Aldohexose
D-Galactose0
D-Glucose6
D-Mannose
Ketohexose D-Fructose L-Sorbose
M.p.& (°C.)
160 87 145
Sirup Sirup 92-5
167 118-20 (monohydrate)
146 83-6 (monohydrate)
132
102-4 159-61
r 120-25 L«JD
(final in H20)
105°
- 2 3 . 7 ° 19°
- 1 6 . 3 ° 34.8°
- 5 8 °
80.2°
52.7°
14.6°
- 9 2 . 4 ° - 4 3 °
Characteristic derivative0
Benzylphenylhydrazone Diphenylhydrazone p-Bromophenylhydrazone Benzylphenylhydrazone Cd Xylonate-CdBr2 double
salt
o-Nitrophenylhydrazone p -Bromophenylhy draz one Benzylphenylhydrazone Anilide
Benzylphenylhydrazone Oxidation to mucic acid Benz y lpheny 1 hy draz one p-Bromophenylhydrazone Oxidation to D-glucaric acid Phenylhydrazone
Anhydro-phenylhydrazone tetraacetate
2,5-Dichlorophenylhydrazone 2,5-Dichlorophenylhydrazone
Ref- erence
(9) (10) (U) (12) (IS)
(14) (15) (16) (17) (18) (19) (18) (18) (20) (18, 21)
(22)
(23) (28)
M.p.
(°C.)
174 204-5 164-5 95
—
168-9 128 128 174 157-8 210-20 163-4 164-6 199-200 123-4
154 117
[a]D (final)
- 1 4 . 6 ° (CH3OH) 14.9° (C5H5N) 10.3° (C2H5OH) - 2 0 . 3 ° (CH3OH)
8.8° (Η,Ο)
- 4 8 ° (CH3OH) 31.5° (C5H5N) - 1 7 . 5 ° ( C5H5N )
46° (C5H5N) -14.3°(C5H5N)
0°
- 4 8 ° (C5H5N) 18° (C5H5N) 33.8°(CBH5N) 12° (CEH5N)
5.3°(C6H5N) - 3 2 . 7 ° (C5H5N)
o » 2
CO
O Ö
2
D-Tagatose
6-Deoxyaldohexosed L-Fucosec
(6-Deoxy-L-galactose) D-Quinovose
(6-Deoxy-D-glucose) L-Rhamnose
(6-Deoxy-L-mannose)
Ketoheptose D -manno -Heptulose Sedoheptulose
(D-aZfro-Heptulose)
134-5
145 139-45
93-4 (monohydrate)
152 Sirup
- 5 °
-76°
29.7°
8.9°
29.4°
2-3°
1,2:3,4-Di -O-isopropylidene- D-tagatose
D-Tagatopyranose penta- acetate
Benzylphenylhydrazone Diphenylhydrazone Phenylosazone·
Phenylhydrazone Phenylosazone'
p-Bromophenylhydrazone a-Hexaacetate
Sedoheptulosan
Sedoheptulosan monohydrate Sedoheptulosan tetrabenzoate
W)
(26)
(12, 26) (26, 27)
(28) (29) (28)
(80) (SD (82) (88) (84)
65-6 132
178 198 186-7 160 189
179 110 155 102 166
72° (H20) 30.2°(CHC18)
14.9° (CH3OH) -15.8°(C6H6N) -95° (C5H5N,
white light) 27° (80%
C2H5OH) 94° (C5H5N, white light)
—
39° (CHCI3) -146° (H20) -134° (Η,Ο) -188° (CHC1,)
β For additional information and details, it is suggested that the following references in particular be consulted : H. Vogel and A. Georg, "Tabellen der Zucker und ihrer Derivate." Springer, Berlin, 1931.
Tollens-Eisner, "Kurzes Handbuch der Kohlenhydrate," 4th ed. Barth, Leipzig, 1935.
(Photo-Lithoprint Reproduction, Edwards Brothers, Inc., Ann Arbor, 1943.)
"Beilsteins Handbuch der organischen Chemie," Vol. 31. Springer, Berlin, 1938.
F. J. Bates and Associates, Natl. Bur. Standards Cire. C440 (1942).
6 Melting points of usual crystalline modifications.
e D-Arabinose, L-galactose, D-fucose, and possibly L-glucose also occur in nature. The physical properties of these sugars and their derivatives are identical with those of the corresponding enantiomorphs listed above except for the sign of the optical rota- tion.
d In addition to the more common 6-deoxyaldohexoses listed here, 6-deoxy-L-talose [J. Schmutz, Helv. Chim. Ada 31,1719 (1948)]
and 6-deoxy-D-allose [M. Keller and T. Reichstein, ibid. 32, 1607 (1949)] have been identified as constituents of cardiac glycosides (see Chapter X).
« Enantiomorph of L-rhamnose phenylosazone.
f Enantiomorph of D-quinovose phenylosazone.
o o
GO >
a a W >
B
O o o d w w
I
a w on
00
00
TABLE I—Continued
9. W. Alberda van Ekenstein and C. A. Lobry de Bruyn, Rec. trav. chim. 15, 225 (1896); 0. Ruff and G. Ollendorf, Ber. 32, oo
3234 (1899). *°
10. C. Neuberg, Ber. 33, 2253 (1900); A. Müther and B. Tollens, Ber. 37, 311 (1904).
11. P. A. Levene and W. A. Jacobs, Ber. 42, 2104, 2472, 2476, 3247 (1909); P. A. Levene and R. S. Tipson, J. Biol. Chem. 115, 731 (1936).
12. O. Ruff and G. Ollendorf, Ber. 32, 3235 (1899); E. Votocek, F. Valentin, and O. Leminger, Collection Czechoslov. Chem. Com- muns. 3, 252 (1931).
IS. G. Bertrand, Bull. soc. chim. [3] 5, 554 (1891) ; 19, 1001 (1898) ; C. S. Hudson and H. S. Isbell, / . Am. Chem. Soc. 51, 2225 (1929).
14. C. Glatthaar and T. Reichstein, Helv. Chim. Ada 18, 80 (1935).
15. P. A. Levene and F. B. LaForge, / . Biol. Chem. 18, 319 (1914); I. Greenwald, ibid. 88, 1 (1930); 89, 501 (1930); L. von Var- ghn Ber. 68, 24 (1935).
16. P. A. Levene and T. Mori, / . Biol. Chem. 83, 803 (1939), P. A. Levene, L. A. Mikeska, and T. Mori, ibid. 85, 785 (1930); R.
E. Deriaz, W. G. Overend, M. Stacey, E. G. Teece, and L. F. Wiggins, / . Chem. Soc. 1879 (1949).
17. P. W. Kent, M. Stacey, and L. F. Wiggins, J. Chem. Soc. 1232 (1949) ; W. G. Overend, M. Stacey, and L. F. Wiggins, ibid. 1358 o
(1949) ; P. A. J. Gorin and J. K. N. Jones, Nature 172, 1051 (1953). §
18. A. Hoffman, Ann. 366, 277 (1909). 0
19. W. H. Kent and B. Tollens, Ann. 227, 221 (1885); "Beilstein's Handbuch der Organischen Chemie,,, Vol. 3, p. 581. Springer,
Berlin, 1921 ; ibid. Vol. 31, p. 303,1938. O 20. R. Gans and B. Tollens, Ann. 249, 219 (1888); Tollens-Eisner "Kurzes Handbuch der Kohlenhydrate," p. 199. Barth, Leipzig, |
1935. g 21. C. L. Butler and L. H. Cretcher, J. Am. Chem. Soc. 53, 4358 (1931).
22. M. L. Wolfrom and M. G. Blair, / . Am. Chem. Soc. 68, 2110 (1946).
28. I. Mandl and C. Neuberg, Arch. Biochem. and Biophys. 35, 326 (1952).
24. T. Reichstein and W. Bosshard, Helv. Chim. Ada 17, 753 (1934).
25. Y. Khouvine and Y. Tomada, Compt. rend. 205, 736 (1937); Y. Khouvine, G. Arragon, and Y. Tomada, Bull. soc. chim.
France [5] 6, 354 (1939).
26. A. Müther and B. Tollens, Ber. 37, 306 (1904).
27. A. Müther, Dissertation, Göttingen, p. 21, 1903.
28. E. Fischer and K. Zach, Ber. 45, 3761 (1912); K. Freudenberg and K. Raschig, ibid. 62, 373 (1929).
29. E. Fischer and J. Tafel, Ber. 20, 2566 (1887); C. Tanret, Bull. soc. chim. France [3] 27, 395 (1902).
80. F. B. LaForge, J. Biol. Chem. 28, 511 (1917).
81. E. M. Montgomery and C. S. Hudson, J. Am. Chem. Soc. 61, 1654 (1939).
82. F. B. LaForge and C. S. Hudson, J. Biol. Chem. 30, 61 (1917).
88. J. W. Pratt, N. K. Richtmyer, and C. S. Hudson, J. Am. Chem. Soc. 74, 2200 (1952).
84. W. T. Haskins, R. M. Hann, and C. S. Hudson, J. Am. Chem. Soc. 74, 2198 (1952).
II. MONOSACCHARIDES: OCCURRENCE, PROPERTIES, SYNTHESIS 8 3
products, being found in gums, hemicelluloses, pectic materials, and bac- terial polysaccharides. Several glycosides yield the sugar on hydrolysis.
Preparation (86). Mesquite gum, from a plant (Prosopis juliflora and related species) common in the southwestern United States, and cherry gum are utilized. Mesquite gum consists of L-arabinose, D-galactose, and 4-0-methyl-D-glucuronic acid in combination, and cherry gum in addition has some D-xylose and D-mannose. By controlled hydrolysis most of the pentose is removed without hydrolyzing the other constituents to any great extent. The L-arabinose is then partially purified by dialysis (86) or ion- exchange procedures (87) and crystallized from ethyl alcohol. Wheat and rye bran, peach gum, Australian black wattle gum, and spent beet pulp have been utilized for the preparation of L-arabinose.
General Discussion. Although calcium chloride compounds of both the a- and ß-anomers have been crystallized (88), only one crystalline anomer of the sugar itself is known, and this has been usually designated as the 0-anomer, following the nomenclature of Hudson.
Neither L- nor D-arabinose is fermentable by yeasts.
D-Arabinose
Occurrence. The sugar is encountered infrequently. Cathartic-acting glycosides (aloins) such as barbaloin, isobarbaloin, nataloin, and homo- nataloin from plants of the genus Aloe (A. barbadensis) yield D-arabinose
(89). The glycosidic union is very resistant to hydrolysis. The sugar occurs in the furanose modification as a constituent of the polysaccharide fraction of tubercle bacilli (40).
Preparation. The D-arabinose has the same configuration as the lower five carbon atoms of D-glucose. Therefore, any of the methods for removing carbon 1 from D-glucose leads to D-arabinose or a derivative. Probably the most convenient method is the oxidation of the easily obtained calcium gluconate by hydrogen peroxide and ferric acetate (41).
85. T. S. Harding, Sugar 24, 656 (1922); E. Anderson and L. Sands, J. Am. Chem.
Soc. 48, 3172 (1926); Org. Syntheses Collective Vol. 1, 60 (1932).
86. E. V. White, J. Am. Chem. Soc. 69, 715 (1947).
87. C. S. Hudson, J. Am. Chem. Soc. 73, 4038 (1951); F. B. Cramer, J. Franklin Inst. 256, 93 (1953).
88. W. C. Austin and J. P. Walsh, J. Am. Chem. Soc. 56,934 (1934) ; J. K. Dale, ibid.
56, 932 (1934); H. S. Isbell and W. W. Pigman, J. Research Natl. Bur. Standards 18.
141 (1937).
89. M. E. Léger, Ann. chim. [9] 8, 265 (1917); C. S. Gibson and J. L. Simonsen, J.
Chem. Soc. p. 553 (1930).
40. M. Maxim, Biochem. Z. 223, 404 (1930); E. Chargaff and R. J. Anderson, Z.
physiol. Chem. 191,172 (1930) ; W. N. Haworth, P. W. Kent, and M. Stacey, J. Chem.
Soc. p. 1211, 1220 (1948).
41. R. C. Hockett and C. S. Hudson, J. Am. Chem. Soc. 56, 1632 (1934);
H. G. Fletcher, Jr., H. W. Diehl, and C. S. Hudson, ibid. 72, 4546 (1950).
84 JOHN C. SOWDEN
D-Ribose
(HO)H2C-C—C—C-CHO I I I
OH OH OH
OH OH
aldehydo -D-Ribose a-D-Ribofuranose Occurrence. D-Ribose and 2-deoxy-D-ribose comprise the carbohydrate constituents of nucleic acids, which are found in all plant and animal cells.
In general, the ribonucleic acids are found in the cytoplasm and the deoxy- ribonucleic acids in the nucleus (Chapter VIII). The 5-thiomethyl analog of D-ribose also is a constituent of yeast nucleic acid.
Preparation (42, 4$)> D-Ribose may be synthesized from D-arabinose by alkaline isomerization, by the glycal synthesis, or through the pyridine- catalyzed epimerization of D-arabonic acid followed by reduction. The sugar also has been prepared by the oxidative degradation of calcium D-altronate (44) and by the nitromethane synthesis from D-erythrose (45).
The best methods for laboratory preparations involve the stepwise hydrolysis of yeast nucleic acid. The original procedure of Levene and Clark which requires the action of ammonia at elevated temperatures and pressures has been greatly improved by Phelps, who uses magnesium oxide as the hydrolytic agent. The hydrolytic products, consisting of a mixture of nucleosides, then are further hydrolyzed by acid to produce D-ribose.
A similar method is based on the enzymic hydrolysis of the yeast nucleic acid (46). Emulsins prepared from sweet almonds, alfalfa seeds, and many sprouted seeds hydrolyze polynucleotides (nucleic acids) to the nucleo- sides. Guanosine (iV-ribosyl-guanine) is produced almost quantitatively and adenosine picrate (picrate of iV-ribosyl-adenine) is likewise obtained in high yield. As in the earlier methods, the nucleosides are hydrolyzed by acids to give D-ribose.
General Discussion (47a). The universal occurrence of D-ribose in all living cells makes this sugar of the greatest interest to biochemists and biologists.
42. F. J. Bates and Associates, Nat. Bur. Standards, Cire. C440 (1942).
48. P. A. Levene and E. P. Clark, J. Biol. Chem. 46, 19 (1921); F. P. Phelps, U. S.
Patent 2,152,662 (1939); L. Laufer and J. Charney, U. S. Patents 2,379,913 and 2,379,914 (1945).
44- C. S. Hudson and N. K. Richtmyer, U. S. Patent 2,162,721 (1939).
45. J. C. Sowden, J. Am. Chem. Soc. 72, 808 (1950).
46. H. Bredereck, M. Köthnig, and E. Berger, Ber. 73, 956 (1940).
47. See: R. W. Jeanloz and H. G. Fletcher, Jr., Advances in Carbohydrate Chem. 6, 135 (1951).
47a. W. G. Overend and M. Stacey in "The Nucleic Acids" (E. Chargaff and J.
N. Davidson, eds.), p. 9. Academic Press, New York, 1955.
H OH
II. MONOSACCHARIDES: OCCURRENCE, PROPERTIES, SYNTHESIS 8 5
Not only is it a constituent of the nucleic acids but also of several vitamins and coenzymes (Chapters VIII and XIII). The sugar occurs in these natural products in the furanose modification. Solutions of ribose probably contain considerable quantities of the furanose form, and the mutarotation is com- plex and exhibits a minimum. Its metabolism is discussed in Chapters XIII and XIV.
D-Ribose is not fermentable by ordinary yeasts.
D-Xylose
H OH H
( H O ) H2C - Ç - < U f c H O -\OH H /
OH H OH HO \ ) _ K 0 H
aldehydo-Ό -Xylose a-D-Xylopyranose Synonyms, Wood sugar; in earlier literature Z-xylose.
Preparation {42, 48). The sugar is prepared from corn-cobs (or many other woody materials) by boiling with acids, fermenting out the glucose with yeasts, and crystallizing the D-xylose from the evaporated solution.
General Discussion. The presence of combined D-xylose in considerable quantities in many important agricultural wastes has stimulated interest in this sugar and its preparation. Cottonseed hulls, pecan shells, corn-cobs and straw have been investigated as sources of the sugar, and several large- scale preparations {49, 50) have been carried out. The sugar crystallizes fairly easily and could be made cheaply, but insufficient uses have been de- veloped to make the manufacture of the sugar of commercial interest. Since it is not fermentable by ordinary yeasts or utilizable by many animals, the value of the sugar is considerably limited. Sheep are able to make use of 94 to 100% of ingested xylose although hogs eliminate 30% in the urine.
The assimilation is greater when the sugar is fed along with large amounts of other materials {50). This pentose is cataractogenic to young rats when fed in large quantities (see under D-Galactose and in Chapter XIV). Many bacteria and certain yeasts are able to ferment the sugar with the formation of important substances. Lactic and acetic acids in yields of 85 to 96% are formed {51) by the action of certain Lactobacilli on D-xylose. Torula and 48. T. S. Harding, Sugar 25, 124 (1923); C. S. Hudson and T. S. Harding, J. Am.
Chem. Soc. 40, 1601 (1918); K. P. Monroe, ibid. 41, 1002 (1919).
49. W. T. Schreiber, N. V. Geib, B. Wingfield, and S. F. Acree, Ind. Eng. Chem. 22, 497 (1930).
60. N. A. Sytchev, Compt. rend. acad. sei. U.S.S.R. 29, 384 (1940).
61. M. Iwasaki, J. Agr. Chem. Soc. Japan 16, 148 (1940).
86 JOHN C. SOWDEN
Monilia yeasts grow well on hydrolyzed straw and corn-cobs and provide a good cattle feed (50).
D-eryfhro-Pentulose H H
(HO)H2C—C—C—C—CH
I I
2(OH) OH OH OSynonyms. D-Ribulose, D-riboketose.
Occurrence. Phosphorylated Ώ-erythro-pentulose is an intermediate in the oxidative pathway of glucose metabolism by yeast or animal tissue and has been recognized as an early product of photosynthesis in plants (see Chapter XIII).
Preparation (52), The ketopentose has been synthesized from D-arabinose by isomerization with pyridine followed by isolation as the crystalline o-nitrophenylhydrazone. The free sugar has not been crystallized. The D-en/£Aro-pentulose 5-phosphate may be obtained by treatment of D-glu- conic acid 6-phosphate with yeast enzymes (Chapter XIII).
L-fhreo-Pentulose OH H
I I
(HO)H2C—C—C—C—CH2(OH)
I I II
H OH O
Synonyms. L-Xylulose, L-xyloketose, urine pentose.
Occurrence. In urine of many cases of pentosuria.
Preparation (53). The sugar has been synthesized by boiling L-xylose with pyridine, removing unchanged L-xylose by crystallization, and iso- lating the h-threo-pentulose as the p-bromophenylhydrazone.
General Discussion. The occasional presence of pentoses in urine was known for a considerable time before the identification of the sugar as L-^Areo-pentulose by Levene and LaForge (54). The precursor of the pentose is believed to be D-glucuronic acid since administration of this substance induces the appearance of the ketopentose in the urine (55). Rats exhibit a significant increase of liver glycogen when fed D-^reo-pentulose but not
52. C. Glatthaar and T. Reichstein, Helv. Chim. Ada 18, 80 (1935).
68. L. von Vargha, Ber. 68,18 (1935); cf. O. T. Schmidt and R. Treiber, Ber. 66, 1765 (1933).
54. P. A. Levene and F. B. LaForge, J. Biol. Chem. 18, 319 (1914); I. Greenwald, ibid. 88, 1 (1930).
55. M. Enklewitz and M. Lasker, J. Biol. Chem. 110, 443 (1935).
II. MONOSACCHARIDES: OCCURRENCE, PROPERTIES, SYNTHESIS 87
when fed the natural L-isomer. The natural isomer is partially utilized by dogs, however (66). (See also Chapter XIV.)
2-Deoxy- D-eryfhro-Pentose H H H (HO)H2C—C—C—C—CHO
OH OH H
Synonyms. 2-Deoxy-D-ribose, ribodesose, thyminose.
Occurrence. In furanosidic combination with purines and pyrimidines in the nucleic acids of plant and animal cells.
Preparation. The preparation of 2-deoxy-D-en/ZAro-pentose by hydrolysis of the natural deoxypentosenucleic acids is tedious and the yields are low.
The nucleic acids first are hydrolyzed enzymatically to deoxyribonucleo- sides (iV-deoxyribofuranosyl purines and pyrimidines). Further mild acidic hydrolysis then liberates the sugar from the purine bases {57). The sugar- pyrimidine linkage, however, is more stable and its hydrolysis by stronger acid is accompanied by destruction of the deoxypentose to levulinic acid.
Direct mercaptanolysis of deoxyribosenucleic acids has been employed to obtain the dibenzyl mercaptal of the deoxysugar {58).
2-Deoxy-D-er^Aro-pentose may be prepared from D-arabinose by the glycal method {59) or from D-erythrose by the nitroolefin synthesis {60).
The two most convenient methods, however, start from D-glucose. In one of these {61), D-glucose is isomerized by alkali (Chapter I) to a mixture of 3-deoxy-D-arafro- and 3-deoxy-D-n'6o-hexonic acids (the D-glucometasac- charinic acids) and the latter are converted to the deoxypentose by oxida- tive degradation. The D-glucometasaccharinic acids also are readily pre- pared by alkaline degradation of the disaccharide laminaribiose or its parent polysaccharide laminarin {62). The second method based on D-glucose
56. H. W. Larson, N. R. Blatherwick, P. J. Bradshaw, and S. D. Sawyer, J. Biol.
Chem. 117, 719 (1937); H. W. Larson, W. H. Chambers, N. R. Blatherwick, M. E. Ewing, and S. D. Sawyer, ibid. 129, 701 (1939).
57. P. A. Levene and E. S. London, J. Biol. Chem. 83, 793 (1929) ; P. A. Levene and T. Mori, ibid. 83, 803 (1929) ; P. A. Levene, L. A. Mikeska, and T. Mori, ibid. 86, 785 (1930); O. Schindler, Helv. Chim. Ada 32, 979 (1949); P. Reichard and B. Estborn, Ada Chem. Scand. 4, 1047 (1950).
58. P. W. Kent, Nature 166, 442 (1950).
59. A. M. Gakhokidze, J. Gen. Chem. (U.S.S.R.) 15, 539 (1945) ; R. E. Deriaz, W. G.
Overend, M. Stacey, E. G. Teece, and L. F. Wiggins, J. Chem. Soc. p. 1879 (1949).
60. J. C. Sowden, J. Am. Chem. Soc. 71, 1897 (1949); 72,' 808 (1950).
61. J. C. Sowden, J. Am. Chem. Soc. 76, 3541 (1954).
62. W. M. Corbett and J. Kenner, J. Chem. Soc. p. 3274 (1954).
88 JOHN C. SOWDEN
involves the preparation of the 3-O-methylsulfonyl-D-glucose and the direct degradation of the latter by alkali to the deoxypentose (62a).
General Discussion (47a, 63). The biosynthesis of 2-deoxy-D-er2/i/iro-pen- tose is believed to occur by aldol condensation between D-glyceraldehyde 3-phosphate and acetaldehyde (Chapter XIII). However, an alternative route, that involves the direct in vivo reduction of D-ribose to its 2-deoxy analog, also has some support (63a).
A remarkable difference between normal sugars and 2-deoxysugars is the extreme ease with which the latter undergo glycoside formation. In further contrast to the normal sugars, 2-deoxy-D-en/ZAro-pentose is readily de- stroyed by aqueous mineral acids which convert it to levulinic acid.
b. Hexoses
D-Ga lactose
H OH OH H I I I 1 (HO)H2C-C— C—C—C-CHO
OH H H OH aldehydo-Ό -Galactose
Synonyms. "Cerebrose," "brain sugar."
Occurrence. The sugar is a frequent constituent of oligosaccharides, notably lactose, melibiose, and raffinose. Polysaccharides which yield galac- tose on hydrolysis include agar, gum arabic, mesquite gum, western larch gum, and many other plant gums and mucilages. A few glycosides have also been reported to yield galactose on hydrolysis (idaein, myrtillin, the cere- brosides, etc.). D-Galactose occurs in glycosidic combination with myo- inositol (64) in sugar beets and with glycerol (65) in certain algae. Crystal- line galactose has been observed on ivy berries.
Galactose polysaccharides from animal sources include the galactogens of the albumin gland of the snail (Helix pomatia), frog spawn, and beef lung (Chapter XII). The cerebrosides and gangliosides, occurring in con-
62a. D.C.C. Smith, Chemistry & Industry p. 92 (1955).
68. For a general discussion of the chemistry of 2-deoxysugars, including 2-deoxy- D-en/Mro-pentose, see W. G. Overend and M. Stacey, Advances in Carbohydrate Chem.
8, 45 (1953).
68a. M. C. Lanning and S. S. Cohen, J. Biol. Chem. 216, 413 (1955).
64. R. J. Brown and R. F. Serro, J. Am. Chem. Soc. 75, 1040 (1953); E. A. Kabat, D. L. MacDonald, C. E. Ballou, and H. O. L. Fischer, ibid. 75, 4507 (1953).
65. H. Colin and E. Guéguen, Compt. rend. 191,163 (1930) ; R. C. Bean, E. W. Put- man, R. E. Trucco, and W. Z. Hassid, J. Biol. Chem. 204, 169 (1953).
.OH H H \ | |X OH
H OH α-Ό -Galactopyranose
II. MONOSACCHARIDES: OCCURRENCE, PROPERTIES, SYNTHESIS 8 9
siderable amounts in brain and nerve tissue, are principally galactosides (Chapter X).
Preparation (66). The most frequently used method requires the hydroly- sis of lactose by acids and the direct fractional crystallization of the galac- tose. A modification of the method involves the removal of the glucose by fermentation with yeasts and the crystallization of the remaining galactose.
Water-soluble gums extractable from the western or eastern larch may serve as sources for the sugar (67).
General Discussion. The usual crystalline modification of the sugar is the a-D-galactopyranose, although the 0-anomer is obtained by crystallization from cold alcoholic solution (68). Galactose and glucose differ only in the configuration of carbon 4, and this difference is accompanied by a greater tendency for galactose to give furanose derivatives. As a result, the mutaro- tation of the galactose isomers does not follow the first-order equation, and considerable quantities of furanose isomers are formed when the sugar is directly acetylated.
Galactose is one of the few sugars other than D-glucose which is found distributed to any great extent in the animal kingdom. In combination with glucose as the disaccharide lactose, it is an important constituent of the milk of mammals. Radioactive tracer experiments have demonstrated that the mammary gland of the cow will convert D-glucose-1-C14 to D-galac- tose-l-C14 during lactose production (69). Similarly, when D-galactose-1-C14 is ingested by rats, D-glucose-1-C14 can be isolated subsequently from the liver glycogen (70). In relation to the mechanism of configurational inver- sion at carbon 4 that results in the interconversion of glucose and galactose, the hydrolysis of glucose 4-phosphate by acid or alkaline phosphatase, or by aqueous acid, produces the original glucose and not galactose (71).
The configurational interconversion in vivo now is known to be achieved enzymically, through the agency of uridine-ö'-pyrophosphoric acid, as described below for lactose-fermenting yeasts.
D-Galactose, like D-xylose, produces cataracts when introduced into the diet of experimental animals (72). Large amounts of D-galactose in the diet 66. T. S. Harding, Sugar 25, 175 (1923); E. P. Clark, Bur. Standards Sei. Papers 17, 228 (1922); G. Mougne, Bull. soc. chim. biol. 4, 206 (1922).
67. A. W. Schorger and D. F. Smith, J. Ind. Eng. Chem. 8, 494 (1916) ; L. E. Wise, P. L. Hamer, and F. C. Peterson, Ind. Eng. Chem. 25, 184 (1933).
68. C. S. Hudson and E. Yanovsky, J. Am. Chem. Soc. 39, 1021 (1917).
69. E.Dimant, V. R. Smith, and H. A. Lardy, J. Biol. Chem. 201, 85 (1953).
70. Y. J. Topper and D. Stetten, Jr., J. Biol. Chem. 193, 149 (1951).
71. H. R. Dursch and F. J. Reithel, J. Am. Chem. Soc. 74, 830 (1952).
72. See: H. S. Mitchell and G. M. Cook, Proc. Soc. Exptl. Biol. Med. 43, 85 (1940);
A. M. Yudkin and H. A. Geer, Arch. Opthalmol. 23, 28 (1940).
90 JOHN C. SOWDEN
of chickens results in violent spasms and eventual death (78). Similar effects are noted in humans who are afflicted with galactosemia due to an inability to assimilate the galactose portion of lactose in milk.
The fermentation of D-galactose by galactose-adapted and lactose- fermenting yeasts has received much study. Leloir (74) and his associates demonstrated that galactose enters the main glycolytic pathways by a direct interconversion of galactose 1-phosphate and glucose 1-phosphate promoted by an enzyme, "galactowaldenase," in the yeast. (See Chapter XIII.)
L-Galactose; DL-Galactose
OH H H OH I I I I (HO)H2C-C — C—C—C-CHO
I I I I H OH OH H
OH H
aldehydo -L-Galactose a-L-Galactopyranose Occurrence. Several polysaccharides including chagual gum, agar-agar, and flaxseed mucilage produce L-galactose on hydrolysis, and, since D-galac- tose is usually present, the DL-galactose is obtained. Galactogen from snails also gives D- and L-galactose on hydrolysis (75).
Preparation. The synthetic methods are the most convenient although the preparation from flaxseed mucilage and agar has been described (76). The separation of L-galactose from natural or synthetic DL-mixtures is accom- plished by the fermentation of the D-galactose by galactose-adapted yeasts or by resolution of the hydrazones formed from optically active 1-amyl-l- phenylhydrazine (77).
The reduction of the readily available D-galacturonic acid to L-galactonic acid and finally to L-galactose may be recommended for the preparation of this sugar. More details are given later in this chapter (p. 128).
78. H. Dam, Proc. Soc. Exptl. Biol. Med. 55, 57 (1944).
74. R. Caputto, L. F. Leloir, C. E. Cardini, and A. C. Paladini, J. Biol. Chem. 184, 333 (1950); L. F. Leloir and C. E. Cardini, Ann. Rev. Biochem. 22, 179 (1953).
75. D. J. Bell and E. Baldwin, Nature 146, 559 (1940).
76. E. Anderson, J. Biol. Chem. 100, 249 (1933); E. Anderson and H. J. Lowe, ibid.
168, 289 (1947); C. Araki, J. Chem. Soc. Japan 59, 424 (1938).
77. C. Neuberg and M. Federer, Ber. 38, 872 (1905).
II. MONOSACCHARIDES : OCCURRENCE, PROPERTIES, SYNTHESIS 91 D-Glucose
H H OH H I I I I (HO)H2C-C—C—C —C-CHO
OH OH H OH aldehydo-Ό -Glucose
Synonyms. Dextrose, blood sugar, grape sugar, corn sugar.
Occurrence. This sugar, in a free or combined form, is not only the most common of the sugars but also is probably the most abundant organic com- pound. It occurs free in fruits, plant juices, honey, blood, lymph, cerebro- spinal fluid, and urine and is a major component of many oligosaccharides
(notably of sucrose), polysaccharides (particularly cellulose, starch, and glycogen) and glucosides.
Preparation (78). D-Glucose (usually called dextrose commercially be- cause of its dextrorotation) is manufactured on a large scale from starch.
Potato starch (Europe) and corn starch (America) are utilized.
Starch, in aqueous suspension, and 0.25 to 0.5% of hydrochloric acid (by weight of starch) are put in a converter. Steam is passed into the con- verter and a pressure of about 40 pounds per square inch is maintained until a 90 to 91 % conversion to glucose has been attained. The acid solu- tion is then passed into tubs and neutralized to a pH of 4.8 with sodium carbonate. Fatty materials originating from the starch are removed by centrifugals, and protein and insoluble carbohydrates subsequently by filtration. Alternatively, fats and proteins are removed from the initial acid hydrolyzate by coagulation with bentonite and the clarified solution is further purified by ion exchange. A cation-exchanger first removes metal ions; then acid is removed by passage over an anion-exchanger. The sugar solution from either process is decolorized and purified by passage through bone black (animal charcoal) and after evaporation to approximately 30°Bé.
(ca. 55 % by weight) is filtered again through bone black. The final filtrate is then evaporated in a vacuum pan. The subsequent treatment depends upon the product desired.
The last stage in the process is the most difficult to carry out on a large scale because the crystallization should take place from aqueous solution (cheapness), the crystals should be homogeneous (at least three forms are possible), and the particular crystals obtained should be easily centrifuged 78. W. B. Newkirk, Ind. Eng. Chem. 16, 1173 (1924); 28, 760 (1936); 31, 18 (1939);
G. R. Dean and J. B. Gottfried, Advances in Carbohydrate Chem. 5, 127 (1950).
CH2OH
Η ^Λ Η
ΗΟΧ^ γίη
H OH a -D -Glucopyranose
160 140
120
100
£ 80 2 13
« 60
I"
40 20
0
-20
100 90 80 70 60 50 40 30 20 10 0 Per cent water
0 10 20 30 40 50 60 70 80 90 100
Per cent dextrose FIG. 1
and washed. The conditions under which the various pyranose forms of D-glucose are stable are illustrated in the above phase diagram (79) of the system D-glucose-water (Fig. 1).
Below 50°C, a-D-glucose-H20 is the stable crystalline phase, but above 50°C. the anhydrous form is obtained. At still higher temperatures, the ß-D-glucose forms the solid phase. Although at any temperature it is usually possible to obtain any form by the addition of the proper seed crystals, this is usually not desirable since the introduction of seed crystals of the more stable modification will result in a change to the latter if equilibrium con- ditions are attained. In the commercial process these conditions are met for the hydrate by cooling the liquid at a concentration of about 40°Bé.
(about 77% by weight) to a temperature of about 50°C, and after seeding heavily with the hydrate allowing it to crystallize while the mass is stirred and slowly cooled. The crystals are then separated by centrifugation and passed through driers.
For the preparation of the anhydrous material, the crystals are developed at higher temperatures in the vacuum pan while the evaporation is taking place. This is done by first evaporating about 15 to 20% of the total batch to a thick sirup (90 % dry substance) and allowing crystals to form spon-
79. W. B. Newkirk, Ind. Eng. Chem. 28, 764 (1936).
Unsaturated solution
jS-Glucose solution A
II. MONOSACCHARIDES: OCCURRENCE, PROPERTIES, SYNTHESIS 9 3
taneously. The remainder of the batch is then used to dilute the seed formed and the evaporation is continued. When the crystals have developed to the desired point, the mass is passed into a centrifuge and the mother liquors removed. During this final stage and during the washing, the proper tem- peratures are maintained to prevent spontaneous formation of the hydrate.
The crystals are finally dried by filtered, warm air.
The ß-D-glucose has proved of some technical interest because of its greater initial solubility. It has been prepared (80) by dissolution in hot pyridine and crystallization at 0°C. The accompanying molecule of pyri- dine is removed at 105°C. The ß-isomer is also prepared (81) by crystalliza- tion from hot acetic acid and recrystallization from water and alcohol at lower temperatures. At temperatures greater than about 115°C, the ß-D-glucose is the stable form in contact with a saturated aqueous solution (see Fig. 1). Because of the high solubility at these temperatures very con- centrated solutions must be used. It is possible to work at somewhat lower temperatures (100°C.) if seed of the α-isomer is excluded. The ß-D-glucose may be prepared by seeding a concentrated glucose solution at 100°C. with ß-glucose and then evaporating it at this temperature to a solid mass (82).
Spray-drying of a hot concentrated glucose solution produces a mixture of the a- and ß-sugar (83).
In industrial circles, the term "glucose" is used to describe a partially hydrolyzed starch product that consists of dextrins, oligosaccharides, mal- tose, and D-glucose. The material is also designated as C.S.U. (corn sirup, unmixed). The commercial material is made by autoclaving aqueous starch suspensions with acids. It has a reducing power usually in the range 40 to 45% of the same weight of D-glucose; the concentration of solid material lies in the range 78 to 85 %.
"Hydrol" is the mother liquor remaining from the preparation of D-glu- cose and corresponding to the "molasses" of cane-sugar refining. The sugar content of a typical hydrol consists of about 65 % of D-glucose and 35 % of disaccharides and higher oligosaccharides. Disaccharides that have been identified (84) in hydrol include gentiobiose, maltose, 6-O-a-D-glucopy- ranosyl-D-glucose ("isomaltose," "brachiose"), α,α-trehalose, cellobiose,
80. R. Behrend, Ann. ΖΊΊ, 220 (1910) ; A. W. Mangam and S. F . Acree, J. Am. Chem.
Soc. 39, 965 (1917).
81. C. S. Hudson and J. K. Dale, J. Am. Chem. Soc. 39, 323 (1917).
82. R. L. Whistler and B. F . Buchanan, J. Biol. Chem. 126, 557 (1938); C. Tanret, Bull. soc. chim. France [3] 13, 733 (1895).
88. A. T . Harding, U. S. Patent 2,369,231 (1945).
84. H. Berlin, J. Am. Chem. Soc. 48,1107, 2627 (1926) ; E . M. Montgomery and F . B . Weakley, J. Assoc. Offic. Agr. Chemists 36,1096 (1953) ; J. C. Sowden and A. S. Spriggs, J. Am. Chem. Soc. 76, 3539 (1954); J. C. Sowden and A. S. Spriggs, J. Am. Chem. Soc.
78,2503 (1956).
94 JOHN C. SOWDEN
and 5-O-0-D-glucopyranosyl-D-glucose. The 6-O-a-D-glucopyranosyl-D-glu- cose arises principally as a residuum of the original starch structure (85), whereas the other disaccharides are formed mainly by acid reversion of the dextrose (86). From amylopectin, hydrolyzed under conditions leading to negligible reversion, 3-O-a-D-glucopyranosyl-D-glucose also has been iso- lated, thus indicating the preformation of this linkage in starch (86a).
D-Mannose
CH2OH
( H O ) H2C - Ç - Ç - Ç - Ç - C H O ( J H 0) l
OH OH H H H 0 V--Γ H
H H aldehydo -D -Mannose ß -D -Mannopy ranose
Synonyms. "Seminose."
Occurrence. Authentic instances of the presence of the free sugar in natu- ral products are lacking, but polysaccharides yielding D-mannose on hydrolysis are frequently encountered. For preparatory purposes, the most important source is the seed of the tagua palm (87), Phytelephas macro- carpa, also known as vegetable ivory. Salep mucilage from tubers of Orchi- daceae, white spruce hemicellulose, and Phoenix canariensis are rich enough sources of D-mannose that they have been used for the preparation of this sugar. Other mannans are proliferated by yeasts and by the red alga Porphyra umbilicalis (88). D-Mannose has also been reported as a con- stituent of ovomucoid, of blood serum globulins, and of tubercle bacilli (Chapter XII).
Preparation (89). Shavings obtained as by-products from the preparation of buttons from the ivory nut (Phytelephas macrocarpa) are considered the best source. The vegetable-ivory shavings are hydrolyzed with acids, and, by a fractionation employing alcohols, the D-mannose formed is separated from other substances and crystallized directly from alcoholic solution or,
85. A. Thompson, M. L. Wolfrom, and E . J. Quinn, J. Am. Chem. Soc, 75, 3003 (1953).
86. W. R. Fetzer, E. K. Crosby, C. E . Engel, and L. C. Kirst, Ind. Eng. Chem. 45, 1075 (1953); A. Thompson, K. Anno, M. L. Wolfrom, and M. Inatome, J. Am. Chem.
Soc. 76, 1309 (1954).
86a. M. L. Wolfrom and A. Thompson, / . Am. Chem. Soc. 77, 6403 (1955).
87. R. Reiss, Ber. 22, 609 (1889).
88. J. K. N . Jones, ./. Chem. Soc. p. 3292 (1950).
89. T. S. Harding, Sugar 25, 583 (1923); E. P . Clark, J. Biol. Chem. 51, 1 (1922);
C. S. Hudson and E . L. Jackson, J. Am. Chem. Soc. 56, 958 (1934); H. S. Isbell, J.
Research Natl. Bur. Standards 26, 47 (1941).
II. MONOSACCHARIDES: OCCURRENCE, PROPERTIES, SYNTHESIS 9 5
alternatively, is converted to the easily crystallizable methyl a-D-man- noside. The direct crystallization of D-mannose is a considerable improve- ment over the earlier methods which separated the sugar as the phenyl- hydrazone.
General Discussion. Both pyranose anomers of the sugar are known, and either may be obtained from aqueous solution by adding seed crystals of the desired form to a supersaturated solution. The importance of having seed crystals is well illustrated by this sugar. The single anomer known for many years was the ß-D-mannose, but in laboratories in which the a-anomer had been obtained, it became very difficult to obtain the more-soluble ß-form. The ß-D-mannose now can be obtained only by very careful exclu- sion of the seed of the a-anomer.
D-Mannose forms an easily crystallizable compound (90) with calcium chloride of the formula CeH^Oe-CaC^^H^O, which exhibits a complex mutarotation with a maximum and which appears to contain the furanose modification of the sugar.
D-Mannose is absorbed by rats at only about 12 % of the rate of D-glucose, and, even after allowance for this difference in absorption, the glycogen deposition in the liver is much smaller for D-mannose than for D-glucose.
This sugar is also much less effective than D-glucose in lowering an existing ketonuria (91). (See also Chapter XIV.)
S2/ra-D-Mannosylguanosine 5'-pyrophosphoric acid has been isolated from yeast where it is presumed to act as a D-mannose donor in the formation of the yeast mannan (92).
D-Fructose H H OH
I I I
( H O ) H2C - C — C — C — C - C K L O H
I I I II 2
OH OH H 0
OH H keto-Ό -Fructose ß (?) -D-Fructof uranose
Synonyms. Lévulose, fruit sugar.
Occurrence (93). D-Fructose is found, usually accompanied by sucrose, in an uncombined form in fruit juices and honey. Apples and tomatoes are
90. J. K. Dale, Bur. Standards J. Research 3, 459 (1929) ; H. S. Isbell, J. Am. Chem.
Soc. 65, 2166 (1933) ; H. S. Isbell and W. W. Pigman, J. Research Natl. Bur. Standards 18, 141 (1937).
91. H. J. Deuel, Jr., L. F . Hallman, S. Murray, and J. Hilliard, J. Biol. Chem. 125, 79 (1938).
92. E. Cabib and L. F . Leloir, J. Biol. Chem. 206, 779 (1954').
93. For a review of the chemistry of D-fructose, see C. P . Barry and J. Honeyman, Advances in Carbohydrate Chem. 7, 53 (1952).
96 JOHN C. SOWDEN
said to have particularly large quantities of the sugar. Sucrose consists of D-fructose and D-glucose in glycosidic union. Plants of the family Com- positae contain large amounts of lévulose polysaccharides (inulins) (Chap- ter XII). It is of interest that many common weeds, e.g., Jerusalem arti- choke, burdock, goldenrod, and dandelion, as well as dahlias and chicory utilize inulins as reserve polysaccharides. The sugar is a frequent constituent of oligosaccharides, often combined with glucose as a sucrose unit, but it rarely occurs in glycosides other than oligosaccharides.
Preparation (4®)> The abundance and wide distribution of D-fructose in natural products, its sweetness, and its resistance to crystallization have stimulated considerable experimental work on methods of preparation.
Most methods depend for the isolation of the sugar on the formation of a difficultly soluble calcium levulate or fructosate in which one mole of the sugar is combined with one of lime. The compound is washed free from im- purities, such as other sugars and inorganic salts, and decomposed to D-fructose and insoluble calcium carbonate by carbonation.
The best source of D-fructose for large-scale purposes is probably the inversion of sucrose by acids or invertase. The separation of the ketose from the concomitant D-glucose then may be accomplished by direct crystalliza- tion, by removal of the D-glucose after oxidation with bromine to D-gluconic acid (ketoses are not affected), or by precipitation of·the calcium fructosate.
Hydrolysis of the natural inulins mentioned above also may serve for the preparation of D-fructose, which is isolated from the hydrolyzate by pre- cipitation of the lime complex. Conditions are patented for preparing D-fruc- tose by the action of alkali on D-glucose {94).
General Discussion. Only one crystalline isomer of the sugar is known, and this is probably a pyranose form. In solution, however, as indicated by evidence obtained from mutarotation studies, a considerable amount of the furanose modification is present. There is no evidence for a true equilibrium between a- and 0-anomers although this condition may be a result of the presence of only a small quantity of the unknown anomer rather than of its complete absence. Upon acetylation, the acetylated acyclic modification is obtained accompanied by the cyclic forms. In natural products the sugar, when combined, is always found as the furanose modification.
Most tests have shown D-fructose to be the sweetest of the sugars, al- though the actual ratios between the various sugars depend to a consider- able extent on the methods and conditions adopted for the comparison.
Compared to a sweetness value for sucrose of 100, that for D-fructose has been reported as varying from 103 to 173. (See also Chapter XIV.) In Table II are given the relative sweetnesses of some sugars and other organic com- pounds.
U. S. M. Cantor and K. C. Hobbs, U. S. Patent 2,354,664 (1944).
II. MONOSACCHARIDES: OCCURRENCE, PROPERTIES, SYNTHESIS 97 TABLE II
RELATIVE SWEETNESS OF SOME ORGANIC COMPOUNDS (95) Compound
Cane sugar (sucrose) D-Fructose
D-Glucose Lactose Maltose Sorbitol Glycerol Invert sugar
Saccharin (D-benzosulfimide) Perillaldehyde-a-anfa'-oxime
2-Amino-4-nitrophenyl n-propyl ether (96)
Relative sweetness 1
1.0-1.5 0.5-0.6 0.27 0.60 0.48 0.48 0.8-0.9 200-700 2000 4000
Intravenously injected D-fructose is assimilated much more rapidly than D-glucose and can be accepted safely at higher rates than the latter without causing undue diuresis, hyperglycemia, or carbohydrate spillage through the urine (97). In the absence of ketosis, diabetics can utilize D-fructose without insulin more efficiently than D-glucose, presumably due to differ- ences in the mechanism of initial phosphorylation of the two sugars (98).
(See Chapter XIV for further discussion.)
L-Sorbose OH H OH
I I I
(HO)H2C-C—C—C — C-CH90H
2 I I I II 2
H OH H O teo-L-Sorbose
OK H a (?) -L-Sorbopyranose Synonyms. Sorbinose; also in earlier literature d-sorbose.
Occurrence (99). L-Sorbose has been reported in the enzymic hydrolyzate 95. C. F. Walton, ''International Critical Tables," Vol. 1, p. 357 (1926).
96. J. J. Blanksma and P. W. M. Van der Weyden, Rec. trav. chim. 59, 629 (1940);
P. E. Verkade, C. P. van Dijk, and W. Meerburg, ibid. 65, 346 (1946).
97. T. Weichselbaum, R. Elman, and R. H. Lund, Proc. Soc. Exptl. Biol. Med. 75, 816 (1950).
98. M. Miller, W. R. Drucker, J. E. Owens, J. W. Craig, and H. Woodward, Jr., J.
Clin. Invest. 31, 115 (1952).
99. For a review of the chemistry of L-sorbose and D-tagatose, see J. V. Karabinos, Advances in Carbohydrate Chem. 7, 99 (1952).
98 JOHN C. SOWDEN
of a pectin from the skin of the passion fruit (Passiflora edulis) (2). Although L-sorbose is found in the fermented juice of mountain-ash berries (Sorbus aucuparia L.), it has been shown to be a secondary product formed by the oxidation of sorbitol (D-glucitol) by bacteria such as Acetobacter xylinum.
Preparation. The biochemical oxidation of sorbitol is the most con- venient source of this sugar, which, as an intermediate in the commercial synthesis of ascorbic acid, is prepared in large quantities by this method.
The early researches by Bertrand (100) showed that sorbitol may be oxi- dized by sorbose bacteria (Acetobacter xylinum Adrian Brown) to L-sorbose.
Yields of 50 to 75 % are reported. By carrying out the fermentation with Acetobacter suboxydans in rotating drums instead of utilizing surface cul- tures of Bertrand's organism, yields of over 90% are obtained (101).
D-Tagatose
? ?H ?H H ^ — ° \ Ç H2O H
(HO)H2C-C—C—C — C-CH2OH κ Λττ
iHÂ À 4 Η θ Ν ^ / Ο Η
H H keto -D -Tagat ose a ( ? ) -D -Tagatopy ranose
Occurrence (99). D-Tagatose has been obtained as a hydrolytic product from a gum exudate of the tropical tree Sterculia setigera (1).
Preparation. D-Tagatose has been prepared by the isomerization of D-galactose (102) with aqueous alkali or pyridine and by the oxidation of D-talitol with Acetobacter suboxydans (103).
L-Fucose OH H H OH
I I I I H X - C — C — C — C-CHO 3
I I I I H OH OH H
ÖH H aldehydo -L-Fucose <*-L-Fucopy ranose Synonyms. 6-Deoxy-L-galactose, L-galactome thy lose, L-rhodeose.
Occurrence. The sugar is found as a constituent of the cell walls of marine 100. G. Bertrand, Compt. rend. 126, 762 (1898).
101. P. A. Wells, J. J. Stubbs, L. B. Lockwood, and E. T. Roe, Ind. Eng. Chem. 29, 1385 (1937).
102. C. A. Lobry de Bruyn and W. Alberda van Ekenstein, Rec. trav. chim. 16, 265 (1897); T. Reichstein and W. Bosshard, Helv. Chim. Ada 17, 753 (1934).
103. E. L. Totton and H. A. Lardy, J. Am. Chem. Soc. 71, 3076 (1949).
II. MONOSACCHARIDES: OCCURRENCE, PROPERTIES, SYNTHESIS 9 9
algae (seaweed) and of a few gUms. It also has been identified in the poly- saccharides of blood group - specific substances from both animal and human sources {104). This sugar seems to be a fairly common constituent of zoöpolysaccharides (Chapter XII).
Preparation (4®, 105). Seaweed (Fucus species or Ascophyllum nodosum) is hydrolyzed by acids and the neutralized hydrolyzate fermented by galac- tose-acclimatized yeasts. The solution after evaporation is extracted with alcohol; after removal of the alcohol, the extracted material is converted to the difficulty soluble phenylhydrazone. The hydrazine groups are then re- moved by reaction with benzaldehyde and the sugar is crystallized from the liquid. The fermentation removes the mannose and galactose which often accompany the L-fucose in seaweeds. The mannose is particularly objectionable since it also forms a difficultly soluble phenylhydrazone.
D-Fucose
Synonyms. 6-Deoxy-D-galactose, D-galactomethylose, rhodeose.
Occurrence and Preparation (106). This rare sugar is occasionally found in the hydrolytic products of glycosides. The roots of certain South and Central American plants (Convolvulaceae), used as purgatives, give resins of a glycosidic nature. Jalap resin (convolvulin) and Scammonium or Tampico jalap (jalapin) are obtained from Tubera jalapae and Ipomoea orizabensis, respectively. Jalapin yields D-glucose, L-rhamnose, D-fucose, and (cüexiro)-11-hydroxyhexadecanoic acid on hydrolysis. Convolvulin on the other hand gives among other products, 3,12-dihydroxyhexadecanoic acid, D-glucose, L-rhamnose, and the 6-deoxy-D-glucose rather than D-fucose.
D-Quinovose
H H OH H I I I I
HeC - C — C — C—C-CHO
LLk in HÔ\p_^ÔH
H OH aldehydo -D -Quinovose a -D -Quinovopyranose
Synonyms. 6-Deoxy-D-glucose, D-glucomethylose, D-isorhamnose, D-epi- rhamnose, isorhodeose, chinovose.
104. H. G. Bray, H. Henry, and M. Stacey, Biochem. J. 40,124 (1946); E. A. Kabat, H. Baer, A. E. Bezer, and V. Knaub, J. Exptl. Med. 88, 43 (1948).
105. E. P. Clark, J. Biol. Chem. 54, 65 (1922); R. C. Hockett, F. P. Phelps, and C. S. Hudson, J. Am. Chem. Soc. 61, 1658 (1939).
106. E. Votocek and F. Valentin, Collection Czechoslov. Chem. Communs. 1, 46, 606 (1929) ; F. B. Power and H. Rogerson, J. Chem. Soc. 101,1 (1912) ; L. A. Davies and R.
Adams, J. Am. Chem. Soc. 50, 1749 (1928); C. Mannich and P. Schumann, Arch.
Pharm. 276, 211 (1938).
