OPTICAL ROTATION AND RING STRUCTURE IN THE
`SUGAR GROUP
`THE OPTICAL ROTATION OF THE VARIOUS ASYMMETRIC
`CARBON ATOMS IN THE HEXOSE AND PENTOSE SUGARS
`
`RP128
`
`By H. S. Isbell
`
`ABSTRACT
`The specific rotations of a-d-gulose ( + 61.6), a-methyl d-guloside (+106) and
`/3-methyl d-guloside ( — 83), which are reported for the first time, complete the
`data necessary for the calculation of the optical rotatory power of each of the
`The values for the
`various asymmetric carbon atoms in the hexose sugars.
`optical rotatory power of the various asymmetric carbon atoms in both the
`hexose and pentose series are calculated first, from the optical rotations of the
`The
`methyl glycosides, and, secondly, from the optical rotations of the sugars.
`values from the glycosides are slightly higher, but of the same order as the values
`obtained from the sugars indicating that the normal forms of d-glucose, d-galac-
`tose, a-d-mannose and a-d-gulose have the same ring structure as the correspond-
`The slightly larger values for the glycosides indicates
`ing glycosides (1, 5).
`that the replacement of the hydroxyl group in the sugars by a methoxy group
`The utilization of the
`alters the rotation of all the asymmetric carbon atoms.
`values given is illustrated by the explanation of certain deviations from Hudson's
`second rule of isorotation and the prediction of the optical rotations of the at
`present unknown hexose sugars and meth}d glycosides.
`
`CONTENTS
`
`I. Introduction
`1. Determination of ring structure by the agreement with or
`deviation from the theory of optical superposition
`2. Determination of ring structure of the glycosides from
`methylation studies
`II. Calculation of the numerical value for the optical rotatory power of
`the various asymmetric carbon atoms
`1. Method of calculation
`2. Calculation of optical rotations of the various asymmetric
`carbon atoms
`3. Summary of results
`III. Discussion of the results
`1. Comparison of the rotations of the methyl glycosides with the
`rotations of the sugars
`2. The prediction of values for the rotation of unknown sugars
`and glycosides
`
`IV. Summary
`
`I. INTRODUCTION
`
`Page
`1041
`
`1043
`
`1044
`
`1046
`1046
`
`1048
`1049
`1049
`
`1049
`
`1051
`1052
`
`In 1875 van't Hoff 1 formulated the rule of optical superposition
`and illustrated it quite plainly in its application to the carbohydrate
`This rule states the optical rotation of the molecule is the
`field.
`algebraic sum of the constituent asymmetric carbon atoms, the
`
`i La Chimie dans L'Espace, van't Hoff, Rotterdam; 1875.
`
`1041
`
`Breckenridge Exhibit 1023
`Breckenridge v. Research Corporation Technologies, Inc.
`
`

`
`1042
`
`Bureau of Standards Journal of Research
`
`[Vol. S
`
`rotations of the individual atoms changing from +a to —a when
`the atomic configuration is replaced by its mirror image.
`Van't
`Hoff illustrated this rule quite plainly in its application to the carbo-
`However, at that time the
`hydrate field as will be discussed below.
`experimental data were lacking to establish its validity in the sugar
`In 1909 the development of experimental carbohydrate
`group.
`chemistry was sufficient for Hudson 2 to apply the superposition rule
`by his method of considering only the rotations of the first asym-
`metric carbon and the rest of the molecule and to determine the
`optical rotation of the first carbon atom and the rotation of the rest
`of the molecule. He compared all kinds of derivatives by his method
`and by this way of comparison showed that the principle of optical
`In order to make comparisons
`superposition holds approximately.
`between substances whose structure differs considerably he made a
`number of rules ("isorotation") or approximations. The correla-
`tion of rotation in the sugar group by him and others showed that
`there exist many deviations 3 from his rules, which indicate that the
`influence of a given group on the rotatory power of the various asym-
`metric carbon atoms is manifested throughout the sugar molecule.
`A test of the theory of optical superposition was anticipated by
`van't Hoff 4 in 1894, who states that when there are several asym-
`metric carbon atoms their action is to be added or subtracted.
`"Thus ^or the four pentose types COH (CHOH) 3 , we should have
`the following rotations:
`
`No. 1
`
`No. 2
`
`No. 3
`
`No. 4
`
`+A
`+B
`+c
`
`+A
`+B
`-C
`
`+A
`-B
`+c
`
`-A
`+B
`+c
`
`and since the sum of No. 2, No. 3, and No. 4 is equal to A + B + C,
`the rotation of arabinose (probably the highest) should be equal to
`the rotations of xylose, ribose, and the expected fourth type taken
`together." 6
`Van't Hoff 's idea may be put in the form of four simultaneous equa-
`tions which contain only three variables, and if the experimental
`values of A, B, and C, determined from any three of the equations
`check the fourth equation, his theory as applied in the given case is
`If one had a similar series of compounds, which
`definitely proved.
`checked, it would be strong evidence that all the compounds in the
`series had similar structures. The realization of the experimental
`proof of this reasoning has not been possible because of the lack of
`knowledge and sufficient experimental data. The problem is far more
`complicated than van't Hoff could anticipate at that early date.
`However, in the light of modern knowledge upon the ring structure
`of the sugars it should now be possible to reach the desired goal if the
`necessary data were available.
`
`2 Hudson, J. Am. Chem. Soc, 31, p. 69; 1909.
`3 Boeseken, The Configuration of the Saccharides, A. W. Sijthoff's, Leyden.
`4 Van't Hoff, The Arrangement of Atoms in Space (translated by Eiloart), Longmans, Green & Co., p.
`160; 1898.
`6 Discovered since, and called lyxose.
`
`

`
`isbeici
`
`Optical Rotation and Ring Structure in Sugar Group
`
`1043
`
`The author is attempting to prepare those compounds necessary for
`the calculation and checking of the optical rotatory power of all the
`different asymmetric carbon atoms in the hexose sugars and methyl
`glycosides. The investigation, which is still in progress, has been
`successful, in that the optical rotations of a-cZ-gulose and a- and
`/3-methyl S-gulosides have been determined.
`These values complete
`the data necessary for the computation of the optical rotation of each
`of the several asymmetric carbon atoms in the hexose sugars and in
`the methyl glycosides. The values obtained for the rotatory power of
`the different asymmetric carbon atoms are of particular interest
`because they are the primary values from which the optical rotation
`of all the normal aldohexose sugars and methyl glycosides may be
`calculated. The numerical values for the at present unknown normal
`forms of d-idose, d-talose, d-allose, and ^-altrose and the correspond-
`ing methyl glycosides are predicted. An attempt is being made to
`prepare and measure the optical rotation of one or more forms of
`If the optical rotations which may be found in the future
`S-idose.
`check the predicted values, it will be strong evidence that all the
`sugars involved in the calculations have similar ring structures.
`
`1. DETERMINATION OF RING STRUCTURE BY THE AGREEMENT
`WITH OR DEVIATION FROM THE THEORY OF OPTICAL SUPER-
`POSITION
`
`At the time when van't HofT first presented the theory of optical
`superposition the reducing sugars were considered to be true alde-
`Subsequently it has been found that the sugars and glycosides
`hydes.
`exist in two isomeric forms (a and /3) which contain an
`additional
`In 1883 Tollens 6 had suggested a ring
`asymmetric carbon atom.
`structure for the reducing sugars, but discovery of the two methyl
`glycosides by Emil Fischer 7 in 1893 marks the beginning of the
`modern concept of the structure of the sugars. The optical rotation
`of the pseudo-aldehydic carbon atom was determined in 1909 by
`C. S. Hudson, who by a series 8 of brilliant researches has developed
`the theory of optical superposition into the most useful tool at the
`disposal of sugar chemists. Hudson 9 has considered the rotation of
`the pseudo-aldehydic carbon as +a in the alpha (dextro) sugars,
`— a in the beta sugars, and the rotation of the rest of the molecules
`as b. The rotation of the a-d-form is equal to b + a and the rotation
`of the /5-(Z-form is equal to b — a. He has shown from the available
`data, first, that the difference between the molecular rotations of the
`a and /3 forms of all the aldehyde sugars and their derivatives (2a) is
`a nearly constant quantity, and, secondly, that the a and (3 forms of
`those derivatives of any aldose sugar in which only the first carbon is
`affected have molecular rotations whose sum is approximately equal
`to the sum (2b) of the molecular rotations of the a and (3 forms of
`Certain exceptions were found to the above rules, par-
`the sugar.
`ticularly in the mannose, rhamnose, and lyxose series, which led to
`
`e Tollens, Ber., 16, p. 921; 1883.
`7 Fischer, Ber., 26, p. 2400; 1893.
`s Hudson, Relations Between Rotatory Power and Structure in the Sugar Group, B. S. Sci. Paper No. 533.
`9 See footnote 2, p, 1042,
`
`

`
`1044
`
`Bureau of Standards Journal of Research
`
`[Vol. s
`
`the hypothesis 10 "that among the known derivatives of mannose and
`rhamnose there occur substances of various ring types (which ac-
`counts for the observed exceptional comparative rotations) and that
`substances belonging to the same ring type show normal comparative
`rotations (which accounts for the normal values)." The hypothesis
`and allocation of the various substances to the different series which
`he postulated was vigorously attacked by Haworth and Hirst. 11 They
`regard a- and /?-mannose as being not necessarily dissimilar in ring
`structure and believe that the divergence in optical rotation may be
`caused by the special arrangement of hydroxyl groups in mannose
`and the related sugars rhamnose and lyxose.
`In their studies they
`found a new form of lyxose whose rotation (—70) is also exceptional.
`However, Hudson's hypothesis has recently received additional sup-
`port in the preparation by Dale 12 of a calcium chloride double com-
`pound of a new form of a-^-mannose whose rotation agrees with the
`rotation calculated by Hudson for a certain ring form of /3-c£-mannose.
`A comparison of the optical rotations of the sugars and glycosides
`only indicates that a given series of compounds have or have not a
`common ring form. The ring structure of said series is assumed to be
`the same as the ring structure of any substance in the series whose
`ring structure is established by other methods. The ring structures
`of these key substances are derived from the results obtained by
`methyl^ation studies.
`
`2. DETERMINATION OF RING STRUCTURE OF THE GLYCOSIDES
`FROM METHYLATION STUDIES
`
`In 1903 Purdie and Irvine 13 showed that the hydroxyl groups in
`methyl glucoside could be replaced by methoxyl groups by means of
`methyl iodide and silver oxide.
`Since all the hydroxyl groups in the
`resulting pentamethyl glucose are blocked the ring structure is as-
`sumed to be fixed. The normal isomeric a and /3 pentamethyl glu-
`coses, when hydrolyzed by acids, are converted into tetramethyl
`Both of the tetramethyl glucoses exhibit mutarotation
`glucoses.
`and give the same final rotatory power which shows that a and /3
`tetramethyl glucose have the same ring structure. Recently Wolfrom
`and Lewis 14 have shown that tetramethyl glucose may be trans-
`formed by dilute alkalies directly to tetramethyl mannose, which
`shows that tetramethyl mannose and tetramethyl glucose have simi-
`Direct evidence on the location of the ring may
`lar ring structures.
`be obtained by the oxidation of the methylated sugars to the corre-
`Charlton, Haworth and Peat 15 found that
`sponding sugar acids.
`those lactones prepared from the normal forms of glucose, galactose,
`mannose, arabinose, and xylose, by first methylating the aldoses and
`then submitting them to oxidation with bromine water, exhibited a
`rapid change in rotation when dissolved in water.
`This rapid
`change 16 indicates that 1,5 lactones were formed.
`This conclusion
`
`io Hudson, J. Am. Chem. Soc, 48, p. 1434, 1926.
`" Haworth and Hirst, J. Chem. Soc, p. 1221; 1928.
`" J. K. Dale, B. S. Jour. Research, 3, p. 459; 1929; J. Am. Chem. Soc, 51, p. 2788; 1929.
`is Purdie and Irvine, J. Chem. Soc, 83, p. 1021; 1903; 85, p. 1049; 1904.
`» Wolfrom and Lewis, J. Am. Chem. Soc, 50, p. 837; 1928.
`" Charlton, Haworth and Peat, J. Chem. Soc, p. 89; January, 1926.
`i« Levene and Simms, J. Biol. Chem., 65, p. 31; 1925.
`
`

`
`:
`
`isbein
`
`Optical Rotation and Ring Structure in Sugar Group
`
`1045
`
`has been confirmed by the degradation of the various methylated
`sugar acids by nitric acid oxidation to the expected products. Thus
`tetramethyl gluconic acid prepared from the normal tetramethyl
`glucose on nitric acid oxidation gave a 70 per cent yield of xylotri-
`methoxyglutaric acid, 17 which indicates that the methylated sugar
`has a 1,5 ring structure.
`The formation of the third methyl glucoside (the distillable so-
`) and other similar compounds indicates
`called 7-form of Fischer 18
`that in a sugar solution an equilibrium 19 may exist between a number
`of different ring forms. As pointed out by Phelps and Purves the
`ring structure of a methylated sugar which might be prepared from
`such a solution would not determine the ring structure of the original
`sugar. When substitution is on the pseudo-aldehydic carbon atom
`as in the glycosides, the oxygen ring is more stable and probably it
`Hence, it may be
`does not migrate upon further methylation.
`assumed that the correct ring structure of glycosides is obtained from
`methylation studies, but that the ring structures of the sugars are
`not established by methylation.
`It has been shown by methylation studies that a- and /3-methyl
`glucosides, 20 a- and /3-methyl galactosides, 21 a-methyl mannoside, 22
`a- and /3-methyl arabinosides, 23 a- and /3-methyl xylosides, 24 and
`The only glycosides
`a-methyl lyxoside 25 have a 1, 5-ring structure.
`whose rotations were used and which have not been shown by methyl-
`ation studies to have a 1, 5-ring structure are the author's newly
`prepared a- and /3-methyl gulosides. 26
`In this article it has been
`assumed that their ring structure is the same as the ring structure
`of the other crystalline glycosides.
`The ring structures of the sugars were allocated by means of the
`concept that there occur different ring forms in the sugar group
`which may be detected by the wide deviation from Hudson's rules
`of isorotation. The rotation of each sugar was compared with the
`rotation of the corresponding glycoside by means of the following
`equations
`
`[M\ D (glycoside) =B' ± 18,500.
`[M] D (sugar) = B ±8,500.
`If the values of B and B f agree approximately it is assumed that
`the two substances have similar ring structures. The only excep-
`tions as previously found by Hudson were in the mannose and
`lyxose series. A comparison of the numerical values shows that
`B ( — 3,100) from a-d-mannose (+30) agrees with the value of
`B' (—3,170) from a-methyl cZ-mannoside ( +79) and hence it is assumed
`
`"Haworth, Hirst and Miller, J. Chem. Soc, p. 2436: 1927.
`is Fischer, Ber., 47, p. 1980; 1914.
`i» Phelps and Purves, B. S. Jour. Research, 3, p. 247; 1929; J. Am. Chem. Soc, 51, p. 2443; 1929.
`20 Haworth, Hirst, and Miller, J. Chem. Soc, p. 2436; 1927.
`2i Haworth, Ruell, and Westgarth, J. Chem. Soc, 125, p. 2468; 1924; Pryde, J. -Chem. Soc, 123, p. 1808;
`1923.
`22 Goodyear and Haworth, J. Chem. Soc, p. 3136; 1927.
`23 Haworth, Hirst, and Learner, J. Chem. Soc, p. 2432; 1927.
`24 Hirst and Purves, J. Chem. Soc, 123, p. 1352; 1923; Phelps and Purves, J. Am.'Chem. Soc, 51, p. 2443;
`1929; also B. S. Jour. Research, 3, p. 247; 1929.
`25 Hirst and Smith, J. Chem. Soc, p. 3147; 1928.
`26 It is planned to methylate the two methyl gulosides and determine their probable ring structure.
`The calculations are published at this time because it will be some time before the methylation studies
`are completed.
`
`

`
`—
`
`1046
`
`Bureau of Standards Journal of Research
`
`[Vol. S
`
`that they belong to the same series. The value of B ( 4- 5,440) from
`iS-^-mannose (—17) does not check the value from the methyl glyco-
`side ( — 3,170) which indicates that it has a different ring structure
`and it is therefore excluded from the calculations. The value of
`B ( — 2,000) from /3-d-lyxose
`( — 70) does not check the value of
`( — 8,760) from a-methyl d-lyxoside and so it is also excluded from
`B r
`the calculations. The values of B and B' as well as' the data used in
`the calculations are given in Table 1.
`
`Table 1 .
`
`Optical rotation of the aldose sugars and glycosides
`
`a-d-glucose '
`/3-d-glucose »
`a-methyl d-glucoside 2 ._
`/8-methyl d-glucoside 2 ._
`a-d-mannose 3 _.„
`
`/3-d-mannose 3
`/3-d-mannose (Dale's) *__
`a-methyl d-mannoside 5
`a-d-galactose J
`/3-d-galactose 1 _.
`
`.
`
`a-methyl d-galactoside 2
`j8-methyl d-galactoside 2
`a-d-gulose 6
`a-methyl d-guloside 6...
`/3-methyl d-guloside e ...
`
`.
`
`/S-d-arabinose L_
`/3-i-arabinose 7
`a-methyl /-arabinoside »
`/S- methyl /-arabinoside ]
`a-d-Xylose J
`
`a-methyl d-xyloside 1...
`/3-methyl d-xyloside 1 ...
`a-d-lyxose '
`/3-d-lyxose 8
`a-methyl d-lyxoside 9__.
`
`inH 2
`
`[Ml™
`
`+113
`+19
`+157. 9
`-32.5
`+30
`
`-17
`-65
`+79
`+144
`+52
`
`+192. 7
`-0.4
`+62.6
`+106
`-83
`
`-175
`+175
`+17.3
`+245. 5
`+92
`
`+153. 9
`-65.5
`+5.5
`-70
`+59.4
`
`+20, 340
`+3, 420
`+30, 630
`-6,300
`+5,400
`
`-3, 060
`-11,700
`+15, 330
`+25, 920
`+9, 360
`
`+37, 380
`-80
`+11, 100
`+20, 600
`-16, 100
`
`-26, 250
`+26, 250
`+2, 840
`+40, 260
`+13, 800
`
`+25, 240
`-10,740
`+825
`-10, 500
`+9, 740
`
`[M)2S
`±8,500=B
`
`+11, 840
`+11, 920
`
`-3,100
`
`+5,440
`-3,200
`
`+17, 420
`+17, 860
`
`+2,
`
`-17, 750
`+17, 750
`
`+5,300
`
`-7, 625
`-2,000
`
`Ring
`from
`methyl-
`ation
`
`Ring
`assigned
`
`±18,500=B
`
`+12, 130
`+12, 200
`
`1,5
`1,5
`
`-3, 170
`
`1,5
`
`+18, 880
`+18, 580
`
`+2,100
`+2,400
`
`+21, 340
`+21, 760
`
`+6, 740
`+7, 760
`
`-8, 760
`
`1,5
`1.5
`
`1,5
`1,5
`
`1,5
`1,5
`
`1,5
`
`1,5
`1,5
`1,5
`1,5
`1,5
`
`1,5
`1,5
`1,5
`1,5
`
`1,5
`1,5
`1,5
`1,5
`1,5
`
`1,5
`1,5
`1,5
`1,5
`1,5
`
`1,5
`1,5
`1,5
`
`1,5
`
`i B. S. Sci. Paper No. 533.
`2 Bourquelot, Ann. Chim., 7, p. 218; 1917.
`3 Levene and Meyer, J. Biol. Chem., 57, p. 329; 1923; 59, p. 129; 1924.
`* Dale, J. Amer. Chem. Soc, 51, p. 2788; 1929.
`« Van Ekenstein, Rec. trav. chim., 15, p. 223; 1896.
`6 These values were taken from the author's work which will be subsequently published. The rotation
`of a-d-gulose was determined from a new calcium chloride double compound of a-d-gulose; the methyl
`gulosides were fractionally crystallized to constant melting point from ethyl alcohol. The rotations may
`be subject to slight revision but are probably correct to ±2°.
`7 Hudson and Yanovsky, J. Amer. Chem. Soc, 39, p. 1035; 1917.
`8 Haworth and Hirst, J. Chem. Soc, p. 1221; 1928.
`» Phelps and Hudson, J. Amer. Chem. Soc, 48, p. 503; 1926.
`
`II. CALCULATION OF THE NUMERICAL VALUE FOR THE
`OPTICAL ROTARY POWER OF THE VARIOUS ASYMME-
`TRIC CARBON ATOMS
`1. METHOD OF CALCULATION
`
`If we assume the 1, 5 ring structure for the sugars, they are repre-
`sented by the formulas I, II, III, IV, V, VI, and VII.
`Since the
`a and /3 forms differ only in the stereoisomeric arrangement of the
`pseudo-aldehydic carbon atom only one form is given. The methyl
`
`

`
`—
`
`isbem
`
`Optical Rotation and Ring Structure in Sugar Group
`
`1047
`
`glycosides differ from the sugars only in that the hydroxyl on the
`first carbon is replaced by a methoxy group.
`
`6
`
`H2OHC
`
`R 5
`H
`. C .
`
`H2OHC
`
`H
`. C .
`
`I
`
`I
`
`H
`. C
`
`H
`
`OH
`. C .H
`
`Aon
`R3
`R2
`Hi
`H
`OH OH H
`C . C . C . C
`H
`H
`OH 1 OH
`
`'
`
`ad-galactose II.
`OH H
`H
`H
`C . C . C . C
`H
`OH OH 1 OH
`
`ad-gulose IV.
`OH H
`C . C . C
`H
`OH
`
`-
`
`'
`
`'
`
`H
`OH
`
`/S-methyl /-arabinose VI.
`
`H O
`
`H
`
`1
`
`1
`
`3
`
`2
`4
`OH H
`H
`C . C . C .
`OH H
`OH
`
`H O
`
`H
`
`ad-glucose I.
`H
`OH OH
`C . C . C . C
`OH H
`H
`
`5H
`
`. C .
`
`I
`
`1
`
`H
`. C .
`
`'
`
`6
`
`H2OHC
`IC
`
`HjOhc
`EC
`
`ad-mannose III.
`OH H
`c . c . c
`H
`OH
`-0
`
`'
`
`'
`
`H
`OH
`
`H
`. C .OH
`
`HC
`
`ad-xylose V.
`H
`H
`OH OH
`c . c . c
`H
`H
`1 OH
`.OH
`-0
`
`'
`
`.
`
`H 1
`
`ad-lyxose VII.
`
`Considering the rotation of the first carbon atom a H27 in the
`sugars or aMe m the glycosides and the rotations of the other carbon
`atoms in order R2 , R3, R4, R5 , the molecular rotations of the sugars
`and glycosides are given by equations which follow. The rotations
`of the various carbon atoms in the hexose series are designated with
`the capital letter R, and in the pentose series they are designated
`with the small letter r; the rotations for the various carbon atoms
`in the glycosides are marked with an accent to distinguish them
`from the values derived from the sugars. The terms in the equations
`are considered to be positive when the hydroxyl group in the sugar
`lies below and negative when it lies above, as shown in Formulas (I)
`to (VI), inclusive.
`
`HEXOSE SUGARS
`(1) a-d-glucose= + a 27+#2 -#3 + #4 + #5= +20,300.
`(2) p-d-g\ucose= -a n+R2-Rz + Ri+R5= +3,420.
`(3) a-d-mannose = + aoi?— #2 — Rz-\-Ri-\-Rb= +5,400.
`(4) /8-d-mannose=— aoff— #2 — -R 3 + fi4+#5=(— 11,700).
`(5) a-d-galactose= +00^+^2-^3-^4 + ^5= +25,900.
`(6) /3-d-galactose = -aoH+Ri-Rs-Ri + R^ +9,360.
`(7) a-d-gulose=+aoH+R2 + Rz-Ri+R5= + 11,100.
`HEXOSE GLYCOSIDES
`5 = +30,630.
`(8) a-methyl d-glucoside = + aM e+R f2-R f
`z + RU+R ,
`5 = -6,300.
`z + R ,
`i + R ,
`(9) 0-methyl d-glucoside= -aM e+R f2-R f
`(10) a-methyl d-mannoside= + aM e-R'2-R'z + R'i + R'5 = + 15,330.
`5 = +37,380.
`(11) a-methyl d-galactoside= + aMe +R ,2-R'z-R ,
`i + R ,
`3 — R ,
`(12) /3-methyl d-ga\a,cto8ide=—aMe +R' 2 — R ,
`i + R't>= -80.
`i + R ,5= +20,600.
`2 + R f3-R ,
`(13) a-methyl d-guloside= +aM e+R ,
`2 + R'z-R'i + R'5= -16,100.
`(14) ^-methyl d-guloside= -aM e+R f
`
`27 The rotations of the first carbon atom in the sugars ao#= ±8, 500) and in the glycosides (aMe =±18,500)
`were calculated by Hudson in 1909, see footnote 2. A value for the rotation of the second carbon atom,
`"the epimeric difference in rotation" was also calculated by Hudson, see footnote 10, but his value (2r2=
`+6,700) differs considerably from the value 2i?2= +15,300 as given in this paper; the difference is due to a
`different allocation of ring structures. The rotation of the fourth carbon atom in the pentose glycosides as
`given by equation (47) was also resorted to in the same article,
`
`

`
`r
`
`=
`
`1048
`
`Bureau of Standards Journal of Research
`
`[voi.s
`
`PENTOSE SUGARS
`(15) a-eZ-xylose= +a H+r2 — r3 + r i = + 13,800.
`(16) /3-cZ-arabinose = —aoR— ?"2 + r 3 + r 4 = —26,250.
`(17) /3-Z-arabinose= +a H+r2 — r3 — r4 = +26,250.
`(18) a-cZ-lyxose = + aojj— r&—
`3 + r4 = +825.
`PENTOSE GLYCOSIDES
`(19) a-methyl <Z-xyloside= + aM e+r'2 — r' z -\-r' 4 = + 25,240.
`(20) /3-methyl d-xyloside = — aMe +r ,
`i = — 10,740.
`3 + r ,
`2 -r ,
`(21) a-methyl Z-arabinoside = —aMe-\-r'2 — r'% — r\= +2,840.
`(22) 0-methyl Z-arabonoside = +aMe +r'2 — r f
`3 — r fi= +40,260.
`(23) a-methyl d-lyxoside = +aM e—r'2 — r' 3 + r'i= +9,740.
`The equations just given may be solved for the optical rotations
`of the different asymmetric carbon atoms by adding or subtracting
`the equations in such a manner as to eliminate all the variables except
`one. The computations are given below:
`
`2. CALCULATION OF OPTICAL ROTATIONS OF THE VARIOUS
`ASYMMETRIC CARBON ATOMS
`HEXOSE SERIES
`
`24. a-eZ-galactose — /3-cZ-galactose
`25. a-cZ-glucose — /3-cZ-glucose
`26. a-methyl cZ-galactoside — /3-methyl eZ-galactoside
`27. a-methyl d-glucoside — /3-methyl cZ-glucoside
`28. a-methyl rf-guloside — /3-methyl cZ-guloside
`29. a-d-glucose— a-cZ-mannose
`30. a-methyl d-glucoside — a-methyl cZ-mannoside
`31. a-eZ-gulose — a-cZ-galactose
`32. a-methyl cZ-guloside — a-methyl cZ-galactoside
`33. 0-methyl d-guloside — /3-methyl d-galactoside
`34. a-cZ-glucose— a ^-galactose...
`35. /3-d-glucose — /3 ^-galactose
`36. a-methyl cZ-glucoside — a-methyl cZ-galactoside
`37. /3-methyl cZ-glucoside — /3-methyl cZ-galactoside
`38. a-cZ-gulose + a-cZ-mannose — 2aon
`39. /3-methyl d-guloside + a-methyl cZ-mannoside
`PENTOSE SERIES
`40. a-methyl d-xyloside — /3-methyl cZ-xyloside
`41. /3-methyl Z-arabinoside — a-methyl Z-arabinoside
`42. a-cZ-xylose — a-cZ-lyxose
`43. a-methyl cZ-xyloside — a-methyl eZ-lyxoside
`44. — (/3-Z-arabinose + a-d-lyxose)+2a0i7
`45. — (a-methyl Z-arabinoside + a-methyl d-lyxoside)
`46. a-J-xylose — /3-Z-arabinose
`47. a-methyl cZ-xyloside — /3-methyl Z-arabinoside
`48. /3-methyl (Z-xyloside — a-methyl Z-arabinoside
`
`2a,Me
`
`=
`16, 540 = 2aOfl-
`=
`16, 880 — 2aon
`= 37, 460
`= 36, 930=2asfe
`= 36, 700 = 2aMe
`=
`14, 900 = 2jR2
`=
`15, 300 = 2R'2
`= — 14, 800 = 2# 3
`= — 16, 780 = 2i?' 3
`= — 16, 020 = 2#' 3
`= — 5, 600=2# 4
`= — 5, 920 = 2# 4
`= —6, 750 = 2i?' 4
`= — 6, 220=2i£' 4
`= 28— 200=2E 5
`=
`— 800=2i2' 5
`
`=+35, 980 = 2aMe
`=+37, 4t20=2aMe
`= + 12, 975 = 2r2
`= + 15, 500 = 2r'2
`= 29 -10, 370=2r3
`= — 12, 580 = 2r' 3
`= — 12, 450 = 2r 4
`= — 15, 020=2r4
`= — 13, 580=2r4
`
`'
`
`'
`
`28 The sum of a-d-gulose plus a-d-mannose=2i?5+2aos'. The numerical value (16,710) of 2aou for the
`hexose sugars was determined by equations (24) and (25). The value of 2R& is obtained by subtracting
`16,710 from the sum of the rotations of a-d-gulose and a-d-mannose.
`29 The sum of j8-6-arabinose and a-d-lyxose=— 2r3+2ao#= — 27,075. The experimental data are not
`available for the determination of 2ooh in the pentose series by means of the original van't Hoff method.
`Since Hudson has shown that the rotation of the first carbon atom aoH for many sugars of different types
`is a nearly constant quantity, the numerical value for 2aon (16,710) whch was found for the hexose sugars
`is used in solving the equation for 2n,
`
`

`
`isbeu]
`
`Optical Rotation and Ring Structure in Sugar Group
`
`1049
`
`3. SUMMARY OF RESULTS
`
`Hexose series
`
`Pentose series
`
`Sugars
`
`Methyl glycosides
`
`Sugars
`
`Methyl glyco-
`sides
`
`aon= +8, 350
`# 2 = +7, 450
`# 3 = -7,400
`fl 4 =-2, 875
`# 5= -100
`
`a jlfe = + 18, 520
`R' 2== +7,650
`R' 3 = -8,200
`RU= -3,240
`R' 5 =
`-400
`
`1 aOH=(+8,350)
`r2= +6,490
`r3= -5, 185
`r4= -6,225
`
`aM e= + lS, 375
`2= +7,750
`r'
`r' 3 = -6,290
`r' 4= -7, 150
`
`» See footnote 29, p. 1048..
`
`III. DISCUSSION OF RESULTS
`A comparison of
`various asymmetric
`the
`the
`rotations
`of
`carbon atoms of the sugars with the corresponding rotations from
`the glycosides shows that in all cases the signs of the rotations agree,
`and that the numerical values are of the same order.
`This shows
`that the assumption that the sugars and methyl glycosides have
`similar structures was justified.
`The rotations of the first three carbon atoms in the pentose
`series are of the same order as the rotations of the corresponding
`atoms in the hexose series, but the rotation of the fourth carbon
`atom in the pentose series differs widely from the rotation of the
`The difference in rota-
`fourth carbon atom in the hexose series.
`tion of the fourth carbon atom in the hexose and pentose series
`was previously made the basis for the allocation of a 1, 4-ring structure
`to glucose by Hudson. Drew and Haworth 31 took exception to
`that allocation on the grounds that the rotations for the pentoside
`and hexoside structures might be different because in the former
`case the fourth carbon atom is joined to one symmetrical and one
`asymmetric carbon atom, while in the latter it is joined to two
`The further conception which was
`asymmetric carbon atoms.
`advanced by Drew and Haworth that the carbon atoms dominating
`the rotatory power of a sugar are those on either side of the ring
`oxygen atom is not substantiated since the rotations of the interme-
`diate carbon atoms 2, 3, and 4 are greater than the adjacent carbon
`atom 5. The value for the rotatory power of the fifth carbon atom
`is very small.
`It can not be explained at the present time.
`
`1. COMPARISON OF THE ROTATIONS OF THE METHYL GLYCO-
`SIDES WITH THE ROTATIONS OF THE SUGARS
`A comparison may now be made between the optical rotations of
`the various asymmetric carbon atoms in the sugars and the corre-
`sponding rotations in the methyl glycosides. The first point is that
`the rotatory power of the individual asymmetric carbon atoms in the
`methyl glocosides is greater than the rotatory power of the corre-
`sponding atoms in the sugars. This indicates that the substitution of a
`
`.» Drew and Haworth, J. Chem. Soc, p. 2303; 1926.
`
`

`
`1050
`
`Bureau of Standards Journal of Research
`
`[Vols
`
`hydroxyl by a methyl group affects the rotations of all the asymmetric
`carbon atoms in the sugar.
`This concept is not in agreement with
`the rigid application of Hudson's second rule of isorotation. Accord-
`ing to that rule the rotation of an a-methyl glycoside of a c2-sugar is
`written b + aMe and that of the alpha form of the parent sugar
`+ aOH- The difference is aMe — a H'
`This difference was found to
`have a fairly constant value, but there are several marked exceptions
`which were noted by Hudson. 32 An explanation of these deviations
`can be derived from the values for the optical rotatory power of the
`various asymmetric carbon atoms in the sugars and glycosides.
`According to the theory of optical superposition the difference in
`molecular rotations between the methyl glycosides and the corre-
`sponding sugars is given by the following equation:
`[M%-[MlD=(aMe ±R' 2 ±R' 3 ±R\±R' 5 )
`~ (o<oh i R% ± -^3 =t R± ± -^5)-
`Since the values of R' are larger than the values of R the value of
`]D — [M]D will vary slightly with the structure of the sugar.
`[Mf
`In the case of arabinose, the sugar which differed most, the equation 33
`results in all the values of r' being of like sign and the values of r
`being different, this gives the maximum deviation from the true value
`of aMe — a H-
`In T]able 2 the values for the difference in molecular rotation of the
`glycosides and sugars (Hudson's aMe ~^oH) are compared with the
`values of aMe ~a H as obtained from the van't Hoff equation (49).
`The value of aM& — a0H as obtained from 1/2 (2aMe — 2a0H ) = approxi-
`mately 10,000.
`
`(49).
`
`Table 2
`
`a-methyl d-glucoside..
`a-d-glucose
`/S-methyl d-glucoside..
`|8-d-glucose
`
`a-methyl d-galactoside.
`a-d-galactose
`0-methyl d-galactoside.
`/3-d-galactose.
`
`a-methyl d-mannoside.
`a-d-mannose
`a-methyl d-guloside
`a-d-gulose
`
`a-methyl d-xyloside....
`a-d-xylose
`/S-methyl /-arabinoside.
`/3+arabinose
`
`[M]d
`
`Hudson's
`dMe—aoH
`[M']d-
`
`ClMe — aoB
`calcula-
`tions
`from the
`van't Hoff
`theory
`
`+30, 630
`+20, 340
`-6, 300
`+3, 420
`
`+37, 380
`+25, 920
`-80
`+9, 360
`
`+15, 330
`+5, 400
`+20, 600
`+11, 100
`
`+25, 240
`+13, 800
`+40, 260
`+26, 250
`
`]
`
`}
`
`}
`
`}
`
`}
`
`}
`
`}
`
`}
`
`+10,290
`
`+ 9, 955
`
`+9, 720
`
`+10, 055
`
`+11,460
`
`+10, 395
`
`+9, 440
`
`+10, 505
`
`+9, 930
`
`+9, 995
`
`+9, 500
`
`+10,035
`
`+11,440
`
`+10,000
`
`+14,010
`
`+10, 720
`
`1 For the beta d-sugars the value given is - {[M']d—[M\d) , but for the/S-/-arabinose the expression is posi-
`tive, which arises from the nomenclature of the a and /3 forms of the d- and I- sugars.
`™ Hudson, J. Am. Chem. Soc, 47 p. 271; 1925.
`33 The small letter r is used to designate the rotations in the pentose series.
`
`

`
`—
`=
`
`:
`
`jsbdi)
`
`Optical Rotation and Ring Structure in Sugar Group
`
`1051
`
`It is evident that the values calculated by the van't Hoff theory
`agree more closely with the value (aMe~<^oH == 10,000) than the values
`calculated by Hudson.
`It should be emphasized that the rotations
`of the sugars and their corresponding methyl glycosides are given
`only approximately by Hudson's equations b ± a n and b ± aMe . The
`value of b from the sugars may or may not equal the value of &
`from the methyl glycosides, depending upon the extent to which the
`differences in the optical rotations of the corresponding asymmetric
`carbon atoms in the sugars and methyl glycosides counteract each
`other. The optical rotations of substances of different structure, such
`as the sugars and glycosides, may be obtained approximately by
`Hudson's rules of isorotation, but it is apparent that more accurate
`data are obtained by comparing substances of like structure.
`
`2. THE PREDICTION OF VALUES FOR THE ROTATION OF UNKNOWN
`SUGARS AND GLYCOSIDES
`
`The values for the optical rotations of unknown aldohexose sugars
`may be obtained from the algebraic sum of the optical rotations of
`the different asymmetric carbon atoms in the sugars; while the optical
`rotations of the methyl glycosides may be obtained from the algebraic
`sum of the optical rotations of the different asymmetric carbon atoms
`in the methyl glycosides. The structures of the at present unknown
`hexose sugars are given by formulas VIII, IX, X, and XI.
`
`H
`OH OH OH
`C . C . C
`H
`
`C . CXOH
`
`H O
`
`-
`
`a-d-Talose (IX)
`H
`H
`H
`OH
`C . C . C . C .
`OH OH H
`
`/
`C
`
`OH
`
`CH 2OH
`
`H
`H
`H
`H
`/
`C . C . C . C . C
`OH OH OH
`
`OH
`
`CHjOH
`
`a-d-Allose (Vlir
`OH H
`OH
`H
`/
`O . C . C . C . C
`OH H
`H
`
`OH
`
`CH 2OH
`
`CH2OH
`
`a-d-Idose (IX)
`
`a-d-Altrose (X)
`
`The rotations of these unknown hexose sugars and glycosides are
`predicted from the following equations
`
`Substance
`
`d-altrose
`
`..
`
`_
`
`.
`
`.
`
`Methyl d-alloside.
`Methyl d-taloside
`Methyl d-idoside..-
`Methyl d-altroside..
`
`= ztaOH+i?2+i?3+i?4+-R5 —
`=zhaoH—R2—Rz—Ra+R5=
`=±aoH—R2+Rs—Ri+Rb= -
`= ±aoH—R2+R3+Ri+R$ =
`= ±am e+R'z+R's+R'i+R'f,
`= ±dMe— R'2 — R'Z— R'i+R'5 =
`= ztaMe—R ,2+R ,3—R'i+R'5 = .--
`= ±<IM e —R ,2+R ,3+R'i+R'5 =
`
`77886°—29-
`
`15
`
`Predicted rotation
`
`Alpha form
`
`Beta form
`
`[M]
`
`D
`
`[«] D
`
`[M]
`
`D
`
`i2
`
`r
`
`+5, 425
`+11, 075
`-3, 725
`-9, 475
`
`+14, 330
`+21,910
`+5, 510
`-970
`
`+30
`+60
`-20
`-55
`
`+75
`+110
`+30
`-5
`
`-11, 275
`-5,625
`-20