OPTICAL ROTATION AND RING STRUCTURE IN THE
`SUGAR GROUP
`
`THE OPTICAL ROTATION OF THE. VARIOUS ASYMMETRIC
`CARBON ATOMS IN THE HEXOSE AND PENTOSE SUGARS
`
`RPl28
`
`By H. S. Isbell
`
`ABSTRACT
`
`The specific rotations of a-d—gulose (+61.6), oz-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
`various asymmetric carbon atoms in the hexose sugars. The values for
`the
`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
`methyl glycosides, and, secondly, from the optical rotations of the sugars. The
`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 cl-glucose, d-gala.c-
`tose, oz-d-mannose and oz—d—gulOSe have the same ring structure as the correspond-
`ing glycosides (1, 5). The slightly larger values for the glycosides indicates
`that the replacement of the hydroxyl group in the sugars by a methoxy group
`alters the rotation of all the asymmetric carbon atoms. The utilization of the
`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 methyl 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 glycosicles
`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 __________________________________________________ __
`
`Page
`1041
`
`1043
`
`1044
`
`1046
`1046
`
`1048
`1049
`1049
`
`1049
`
`1051
`1052
`
`I. INTRODUCTION
`
`In 1875 va.n’t Hoff 1 formulated the rule of optical superposition
`and illustrated it quite plainly in its application to the carbohydrate
`field. This rule states the optical rotation of the molecule is the
`
`the constituent asymmetric carbon atoms,algebraic sum of the
`
`
`1 La Chimie dans L’Espace, van't Hot}, Rotterdam; 1875.
`
`1041
`
`MYLAN - EXHIBIT 1023
`
`MYLAN - EXHIBIT 1023
`
`

`
`1042
`
`Bureau of Standards Jowrnal of Research
`
`(Vol. 3
`
`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-
`hydrate field as will be discussed below. However, at that time the
`experimental data were lacking to establish its validity in the sugar
`group.
`In 1909 the development of experimental carbohydrate
`chemistry was sufficient for Hudson” 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
`superposition holds approximately.
`In order to make comparisons
`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?‘
`rom 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 for the four pentose types COH (CHOI-I)3, We should have
`the following rotations:
`
`No. 1 No. 2 No. 3 No. 4
`
`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.” 5
`Van’t Hofl’s idea may be put in the form of four simultaneous equa-
`tions which contain 0111
`three variables, and if the experimental
`values of A, B, and C,
`etcrmined from any three of the equations
`check the fourth equation, his theory as applied in the given case is
`definitely proved.
`If one had a similar series of compounds, which
`checked, it would be strong evidence that all the compounds in the
`series had similar structures. The realization of the experimental
`roof of this reasoning has not been possible because of the lack of
`mowledge and suflicicnt ex erimental data. The problem is far more
`complicated than van’t I. oli 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 I Iiulson, J. Am. Chem. Soc., 31. p. 69; 1909.
`3 Bccseken, The Configuration of tho Saccharides, A. W. SijthoII’s Leyden.
`mf) \I:i_i:_"t 11011, The Arrangement of Atoms in Space (translated by lflilonrt), Longmans, Green & Co., 1).
`;
`:4. ..
`n
`5 Liisczsvercel since, and called ly::c:.-=2.
`
`

`
`Iabetlj
`
`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 asyinmetric 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-d-gulose and a- and
`fi—methyl d-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 t e optical rotation
`of all the normal aldohexose sugars and methyl glyeosidcs may be
`calculated. The numerical values for the at present unknown normal
`forms of d-idose, d-talose, cl-allose, and d-altrose and the correspond-
`ing methyl glycosides are predicted. An attempt is being made to
`pre are and measure the optical rotation of one or more forms of
`(1-1 ose.
`If the optical rotations which may be found in the future
`check the
`redicted values, it will be stron evidence that all the
`sugars invo ved in the calculations have simi ar 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 Hoff first presented the theory of optical
`superposition the reducing sugars were considered to be true alde-
`hydes. Subsequently it has been found that the sugars and glycosides
`exist in two isomeric forms (a and B) which contain an
`additional
`asymmetric carbon atom.
`In 1883 Tollens 6 had suggested a ring
`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—a.ldehydic carbon atom was determined in 1909 by
`C. S. Hudson, who by a series 3 of brilliant researches has developed
`the theory of optical superposition into the most useful tool at the
`disposal of sugar chemists. Hudson” has considered the rotation of
`the pseudo-aldehydic carbon as +a in the alpha (dextro) sugars,
`-a 1n the beta sugars, and the rotation of the rest of the molecules
`as b. The rotation of the a-cl-form is equal to b+a and the rotation
`of the {3—cl-form is equal to 6-0,. He has shown from the available
`data, first, that the difierence between the molecular rotations of the
`a and B forms of all the aldehyde sugars and their derivatives (2a) is
`a nearly constant quantit , and, secondly, that the a. and ,6 forms of
`those derivatives of any a dose 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
`the su ar. Certain exceptions were found to the above miles par-
`ticular y in the mannose, rhamnose, and lyxose series, which led to
`
`6 Tollens, Ben, 10, p. 921; 1883.
`7 Fischer. Ben, 30. p. 2400; 1893.
`8 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 3
`
`the hypothesis 1° “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
`rota.tions (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.“ They
`regard a.- and fl-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 the
`found a new form of lyxose whose rotation (- 70) is also exceptiona .
`However, Hudson’s hypothesis has recently received additional sup-
`port in the preparation by Dale 1’ of a calcium chloride double com-
`pound of a new form of O.-d'IIl8.I1I10Se Whose rotation agrees with the
`rotation calculated by Hudson for a certain ring form of B-d-mannose.
`A comparison of the optical rotations of the sugars and glycosides
`only indicates that a
`'ven series of compounds have or have not a
`common ring form. T e 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
`methylation studies.
`
`2. DETERMINATION OF RING STRUCTURE OF THE GLYCOSIDES
`‘
`FROM METHYLATION -STUDIES
`
`In 1903 Purdie and Irxdne 13 showed that the hydro}:
`1 groups in
`methyl glucoside could be re laced by methoxyl groups by means of
`methyl iodide and silver oxi e. 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 ,8 pentamethyl glu-
`coses, when h drolyzed by acids, are converted into tetramethyl
`glucoses. Bot 1 of the tet-ramethyl glucoses exhibit mutarotation
`and give the same final rotatory power which shows that o. and [3
`tetramethyl glucose have the same ring structure. Recently Wolfrom
`and Lewis 1" have shown that tetramethyl glucose may be trans-
`formed by dilute alkalies directly to tetrameth l mannose, which
`shows that tetramethyl mannose and tetramethy glucose have simi-
`lar ring structures. Direct evidence on the location of the ring may
`be obtained by the oxidation of the methylated sugars to the corre-
`sponding sugar acids. Charlton, Haworth and Peat “" found that
`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 “‘ indicates that 1,5 lactones were formed. ‘This conclusion
`
`10 Hudson, J. Am. Chem. ‘Soc., 48. p. 1434. 1926.
`11 Haworth and Hirst, J. Chem. Soc., 1). 1221'. 1928.
`1* J. K._Dale, B. 5. Jour. Research, 3, p. 459; 1929; J. Am. Chem. Soc., 51, p. 2788; 1929.
`33 Purdie and Irv1ne._ J. Chem. Soc., 83. p. 1021', 1903: 85. p. 1049; -1904.
`14 Wolfrom and LGWIS, J. Am. Chem. Soc., 50, p. 837; 1928.
`15 Charlton, 1Ia\_vorLh and Peat J. Chem. Soc., p. 89; January, 1926.
`1° Levcne and Sxmms, J. Biol. Chem, 85, p. 31; 1925.
`
`

`
`maul
`
`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 ex ected 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," which indicates that the methylated sugar
`has a 1,5 ring structure.
`.
`The formation. of the third methyl glucoside (the distillable so-
`called 7-form of Fischer 13) and other similar compounds indicates
`that in a sugar solution an equilibrium *9 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
`does not migrate upon further methylation. Hence,
`it may be
`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 methylat-ion studies that oz- and 6-methyl
`glucosides,” oz- and B-methyl gaalactosides,“ oz-methyl mannoside,”
`a- and B-methyl arabinosides,
`a— and )3-methyl xylosides,“ and
`a-methyl lyxoside 25 have a 1, 5—ring structure. The only glycosides
`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 )8-methyl gulosides.“
`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:
`
`[]l[],, (glycoside) = B’ 5.: 18,500.
`
`[MD (sugar) =B i 8,500.
`
`If the Values of B and B’ a ree approximately it is assumed that
`the two substances have simi ar ring structures. The only excep-
`tions as previously found by Hudson were in the mannose and
`1 xose series. A com arisen of the numerical values shows that
`(-3,100) from a. mannose (+30) agrees with the value of
`B’ (- 3,170) from a-methyl d-mannoside (+79) and hence it is assumed
`
`17 Haworth Hirst and Miller. J. Chem. Soc., p. 2436: 1927.
`.
`15 Fischer. iaei-., 47, p. 1980; 1914.
`1' Phelps and lfurves, B. S. Jour. Research, 3, p. 247; 192); J. Am. Chem. Soc.-., 51, p. 2443; 1929.
`W Haworth, mist, and Miller, J. Chem. Soc., p. 2436; 1927.
`wgsfifiworth. Ruell, and Westgarth, J. Chem. Soc., 125. p. 2468; 1924; Pryde, J. Chem. Soc., 123, p. 1308;
`9? Goodyear an_d Haworth, J. Chem. Soe., p. 3136; 1927.
`_
`33 Haworth, Ilirst, and Learner, J. Chem. Soc., 11. 2432; 1927.
`14 Hirst and Purves, J. Chem. Soc., 128, p. 1352; 1923; Phelps and Purves, J. Am._Chem. Soc, 51, p. 2443;
`1929; also B. S. Jour. Research. 3, p. 247; 1929.
`15 Hits: and Smith, J. Chem. Soc., p. 3147; 1028.
`*9 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.
`
`..._—,r.r... - ._x
`
`

`
`1046
`
`Bureau of Standards Journal of Research
`
`[Vol.5
`
`that they belong to the same series. The value of B (4-5,440) from
`B—d-mannose (- 17) does not check the value from the methyl glyco-
`side (—3,170) which indicates that it has a diflerent ring structure
`and it is therefore excluded from the calculations. The value of
`B (—2,000)
`from /3-(Z-lyxose (-70) does not check the value of
`B’ (—8,7 60) from a—methy1 cl-lyxoside and so it is also excluded from
`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
`
`
`M20
`
`i=-’B
`
`*L's
`
`Ri
`
`”“a%Eoi'
`
`"*“g“°“
`
`or-d-glucose 1............................. --‘ +113
`+3. 420
`B-d-glucose‘ .... --_....................... --I
`+19
`a-methyl d~glueos1de 5___________________ --l +157. 9 +30, 630 ........ --
`B-methyl d-clucoside 9................... --*.
`-32» 5
`-6. 300 ........--
`a~d-mannose 3 ........................... _-l
`+30
`+5, 400
`
`.................. --
`.................. --
`
`.................. .-
`
`1, 5
`1, 5
`1, 5
`1. 5
`1, 5
`
` 20
`
`
`
`
`-—3,06O
`-17
`-,
`fivddziannose 3 ...... -_
`-11, 700
`-65
`;
`,8-d-mannose (Dale’s)
`+15, 330
`+79
`at-methyl d-mannoside 5
`+25, 920
`a-d-galactosel...................... --% +144
`+9. 360
`B-d-galactose 1...........................--;
`+52
`crmethyl
`-galactosidc ‘-'_________________-_l +192. 7 +37, 380
`8-methyl
`-galactosido 1_________________--
`--0. 4
`-80
`a-d-gulose °.... --_. ...... --
`-
`+62. 6 +11, 100
`an-methyl d~guJos1de G...
`.
`+106
`+20, 600
`fl-methyl d-guloside 5---
`-
`-83
`-16, 100
`
`
`
`
`
`-26, 250
`-175
`B-d-arabinose 1.. ......................... --
`+26, 250
`+175
`i9-l-arabinose 7........................... -.
`+-2,840
`+17. 3
`a-methyl I-arabinoside I................. --
`5- methyl barabinoside 1_________________ -- +ms. 5 +40, 260
`oz-d-Xylose 1............................. --
`+92
`ii +13, 800
`an-methyl d-xyloside 1.................... --
`+153. 9 +25, 240
`B-methyl d-xyloslde 1-
`J
`-55. 5
`-10 740
`V
`a-d~1yxose 1----
`I
`+5. 5
`+825
`-;
`,
`.
`(8-d-lyxose 5----
`3
`-70
`, -10, 500
`a-methyl d-lyxoside 9.....................-~
`+59. 4
`+9. 740 ........--;
`1 B. S. Sci. Paper No. 533.
`. 218; 1917.
`1 Bourquelot. Ann. Chim., 7,
`.hem., 57, p. 329; 1923; 59, p. 129; 1924.
`3 Levene and Me er, J. Biol.
`4 Dale, J. Amer. hem. Soc., 51. p. 2788; 1929.
`_
`_
`I Van Ekenstein, Rec. mw. chim., 15,
`. 223; 1896.
`I These values were taken from the ant or’s work which will be subsequently published. The rotation
`of a-d-gulose was determined from a new calcium chloride double complound oi ae-d-
`ose; the methyl
`gulosides were froctionally crystallized to constant melting point. from et, yl alcohol.
`he rotations may
`be subject to slight revision but are probably correct to i2°.
`7 Hudson and Yanovsky, J. Amer. Chem. Soc., 39, p. 1035; 1917.
`9 Haworth and Hirst, J. Chem. Soc., p. 1221; 1928.
`9 Phelps and Hudson, J. Amer. Chem. Soc., 48, p. 503; 1926.
`
`. - ............. ..
`1, 5
`1, 5
`1, 5
`1, 5
`1, 5
`1, 5
`1, 5
`1, 5
`1., 5
`
`1, 5
`1, 5
`1,5
`J, 5
`1, 5
`1, 5
`1, 5
`1, 5
`«
`F‘~ 91
`i ........ --
`
`I
`-8, 760 E
`
`3.: (II
`
`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
`ac and [3 forms differ only in the stereoisomeric arrangementof the
`pseudo-aldehydic carbon atom only one form is given. The methyl
`
`

`
`I
`2
`3
`4
`5
`6
`OH H
`H
`H
`H
`H20HO.C.C.G.C.O
`
`I
`OH II
`OH I OH
`
`O
`and-glucose I.
`H
`OH OH
`H
`H
`Ha0HG . O . O . C . C . C
`
`I
`OH H H
`I OH
`
`O
`ad-mannose III.
`OH H
`H
`H
`H
`C . C .
`H . C . C
`I
`OH H
`OH I OH
`
`0
`ad-xylose V.
`131
`11'
`OH OH
`H . C . C . O . C . C
`I
`OH H
`H
`I OH
`
`O
`ad-lyxose VII.
`
`H
`
`R2 A03
`R3
`R4
`R5
`6
`OH OH H
`H
`H
`I.I:0HO.C.C.C‘-.O.C
`I
`H
`H
`OH I OH
`
`0
`ad-galactose II.
`H
`OH H
`H
`H
`_
`H:OIIO . C . C .
`C‘
`. C . C
`I
`H
`OH OH I OH
`
`0——————-
`ad-gulose IV.
`OH OH H
`H
`H . C . C . O . G . C
`I
`H
`H
`OH I
`
`
`0
`flmethyl I-arabinose VI.
`
`H
`OH
`
`Considering the rotation of the first carbon atom a.oH27 in the
`sugars or am in 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
`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.
`
`IIEXOSE SUGARS
`(1) a~d-glucose= + GoH+ R2 — R;+ 134+ R5= +20,300.
`(2) 13-d-glucose = '— 0011+ — R3 + R4 + R5= + 3,
`at-d-lI).aI1I10S6= + (log-‘ 2-‘ R3 + R4 + R5 = + 5,400.
`(4)
`;3-d-ma,nnose= ~—aog——R2——R3+ R4+R,r,= (— 11,700).
`(5) a—d-galactose = +001: + H2 — R3 -— R4 + R5 = + 25, 900.
`(6) B-d-galactose= ——aoH+ Rz— R3 -R4+ R5 = + 9,360.
`or-d-gulose= -I-Gag-l-‘R2-I‘ 533-" 134+ R_v,="- + 1 1,100.
`
`HEXOSE GLYOOSIDES
`I8) a-methyl d-g1ucoside== +am+R'-2 - R’;;+ R’4+ R’5= + 30,630.
`9) 3-methyl d-g1ucoside= —aM,+ R’; — R’; +R’4+R’5= — 6,300.
`(10) as-methyl d-ma.nnoside= +aM.— R’2——R/3+ R’4+R’5== + 15,330.
`(11) oz-methyl d-galactoside= +aM.+ R’;—— R’3— R’; + R’5= + 37,380.
`853 ”““elt’l §‘g?l“°”3S‘“ef ”“’"£¢R’?“'27R’?“=23282)
`a-me y
`-g osie= a.+ +
`——
`+ -=+
`.
`(I4) ,8-methyl d-guloside= —ailvl.+R’§+ R’:——R’:+R’:= — 16:100.
`7’ The rotations ofthe first carbon atom in the sugars don-:l:8.500) and in tho lycosides (¢1.lla":l=18y500)
`were calculated b Hudson in 1909, see footnote 2. A value for the rotation o the second carbon atom,
`"the epimeric di erence in rotation” was also calculated by Hudson, see footnote 10, but his value (27:-
`—l;6.700) differs considerably from the value 2R2=+15,300 as given in this paper; the difference is due to a
`difierent allocation ofring structures. The rotation of the fourth carbon atom in the pentose glycosides as
`given by equation (-17) was also resorted to in the same article.
`
`

`
`1048
`
`Bureau of Standards Journal of Research
`
`[Vol.3
`
`PENTOSE SUGARS
`
`(15) 0-d-XY10§e = + aoH+T2 -' ?'3+7'4= 4-13,800.
`(16)
`)3-d-arab_1nose == — am;— 7'3 + r_»,+ r4 = — 26,250.
`(17)
`;3-l-at-ab1nose= + ao;;+ r2— r3— r4= + 26,250.
`(18) a-d-lyxosc = + am; — r2 — r3+r4= +825.
`
`PENTOSE GLYC OSIDES
`
`(19) as-methyl d-xy1oside= + a.u.+w-'2 -7-'3 + r’4= + 25, 240.
`(20)
`[3—methyl d-xy10side= -— a,m+ r’2 -—- r’3+ r’4= — 10, 740.
`(2 1) oz-methyl Z-arabinoside = —- a.M.+ r’-2 — r’3 — r’4= + 2,840.
`(22) B-methyl l-a.rabonoside= +a_u.+r’g—r’a—r’4= + 40,260.
`(23) a-methyl d-1yxoside= + aM.—— 7-’; — r’; + r’; = + 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
`
`IIEXOSE SERIES
`
`16, 540=2a0H
`24. o:-d-ga.1a,ctose—- 3-d—ga1actose ...................... -_
`25. at-d-glucose-fi—d-glucose ......................... -- = 16, 880=2aog
`26. a-methyl rl-ga1actoside- B-methyl d-galactoside _____ __ = 37, 460=2aM,
`27. oz-methyl d-g1ucoside—B-methyld-glucoside ......... -_ = 36, 930=2a,,,.
`28» av-methyl d-gu1oside—fl-methyl d-guloside .......... -- = 36, 700=2aM,
`29. an-d-g1ucose—a-d-mannose ........................ -_ = 14, 900:-ZR,
`30. a-methyl d-g1ucoside—a-methyl d-mannoside _______ __ = 15, 300=2R’2
`31. a—d—gu1ose-—a—d-galactose_________________________ -_ = -14, 800=2R,,
`32. an-methyl d-guloside—a-methyl d-galactoside ........ -_ = -16, 780=2R'a
`33. B-methyl d-guloside—B-methyl d-galactoside ........ __ = — 16, 020=2R’,-,
`34. oz-d-g1ucose—a d-galactose ........................ - - = -5, 600=2R4
`35.
`)3-d-g1ucose—)6 d-galactose ........................ -_ = -5, 920=2R4
`36. oz-methyl d-g1ucoside~—a-methyl d-galactoside ....... __ = -6, 750=2R’4
`37.
`,8-methyl d-glucoside—fl-methyl d-galactoside_______ _- = —-6, 220=2R’4
`38. a—d-gu1ose+a-d-mannose—2aog___________________ -_ = 99—200=2R5
`39. )9-methyl d-gu1oside—l—a-methyl d-mannoside ........ -_ = —800=2R'5
`PENTOSE SERIES
`
`40. a-methyl d-xyloside-fl-methyl d-xyloside ........... -- = +35, 980=2aM.
`41.
`,3—methy1 l-ara.binoside—a-methyl l-arabinosidc ______ -- = +37, 42O=2a.M,
`42. oz-d-xylose—a:-d-lyxose ............................ _ _ = —|- 12, 975: 2r;
`43. cc-methyl d-xyloside—a-methyl d-lyxoside ___________-_ = + 15, 5O0=2r’2
`44. — ()3-Z-arabinose+a-d-lyxose) + 2aog _______________ _ _ =?”— 10, 370=2r3
`45. -- (oz-methyl l-arabinoside +a-methyl d-lyxoside) - _____ - = — 12, 580-—-2r’;
`46. a—d-xyl0se—B-l-arabinosc __________________________ -_ = — 12, 450=2r.,
`47. ¢x—mcthyl d-xyloside—fi-methyl Larabinoside _________ _- = -15, 020=2r.;’
`48. 5-methyl d-xy1oside—a-methyl Z-arabinoside ......... _- = —— 13, 580=2-r4’
`
`15 The sum of a-d-gulose plus a-d-rnannose==2R5+2aorr. The numerical value (16,710) or 2mm for the
`hcxose sugars was determined by equations (24) and (25). The value or 2R5 is obtained by subtracting
`16,710 from the sum of the rotations of a-d-gulose and a-d-mannose.
`7' The sum of B-b-arabinose and a—d-lyxose= -21’:-I-2£lou=—27,075. The experimental data are not
`available for the determination of may in the
`ntose series by means of the original van’: _IIoff method.
`Since Hudson has shown that the rotation of t e first carbon atom non for many sugars of difierent types
`isa nearly constant quantity. the numerical value for may (16,710) whch was found for the hexose sugars
`is used in solving the equation for Zn.
`
`

`
`Isbetl]
`
`Optical Rotation and Ring Structure in Sugar Group
`
`1049
`
`3. SUMMARY OF RESULTS
`
`Hexose series
`
`Pentose series
`
`Sugars
`
`Methyl glycosides
`
`Sugars
`
`aog=+8, 350
`R3= +7, 450
`R3:-7, 400
`R4=—2, 875
`I35:
`-100
`
`(lM¢=-I-18, 520
`R’2= +7, 650
`R’.-,= -8, 200
`R’4= -3, 240
`R’5=
`-400
`
`I
`=
`
`1aoH= (+8,
`r3= +6, 490
`r3= -5, 185
`n: -6, 225
`
`l See footnote 29, p. 1048..
`
`III. DISCUSSION OF RESULTS
`
`Methyl glyco-
`sides
`
`aM¢=+18,
`r’2= +7, 750
`r’3= --6, 290
`r’4= -7, 150
`
`\,
`|
`
`
`
`1
`
`the various asmetric
`the rotations of
`A comparison of
`carbon atoms of the sugars with the corresponding rotations from
`the g1 cosides shows that in all cases the signs of the rotations agree,
`and t at the numerical values are of the same order. This shows
`that the assumption that the sugars and methyl glycosides have
`similar structures was justified.
`three carbon atoms in the pentose
`The rotations of the first
`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
`fourth carbon atom in the hexose series. The difference in rota-
`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 g ucose 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
`asymmetric carbon atoms. The further conception which was
`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 1S 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
`
`,3‘ Drew and Haworth, J. Chem. Soc-., p. %03; 1926.
`
`

`
`1050
`
`Bureau of Standards Journal of Research
`
`[Vol.3
`
`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 oz-methyl glycoside of a d-sugar is
`Written b+aM,,. and that of
`the alpha form of the parent sugar
`b+aoH. The difference is aM,—aog. This difference was found to
`have a fairly constant value, but there are several marked exceptions
`which were noted by Hudson.” 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:
`
`(49).
`
`[.M']D~[M]D=(aM,:l:R'g:hR'3:l:R'4:l:R’5)
`—(aoHjZ.R22iZR3ZlZ1242iZ.R5).
`
`Since the values of R’ are larger than the values of R the value of
`[M’]D—[M]D will vary slightly with the structure of "the sugar.
`In the caseof arabinose, the su ar which difiered most, the equation 33
`results in all the values of r’
`eing of like sign and the values of r
`bfing difl'erent, this gives the maximum deviation from the true value
`'
`0 03Me“0»oH-
`In 'l}ab1e 2 the values for the difference in molecular rotation of the
`glycosides and sugars (Hudson’s am-aog) are compared With the
`values of aM.,—aoH as obtained from the van’t Hoff equation (4:9).
`The value of am,-—aoH as obtained from 1/2 (2a,.,,,—2aog) =approxi-
`mately 10,000.
`
`TABLE 2
`
`I aMe—UOE
`Hudson's -
`calcula-
`El
`I13
`0 —ll
`[i1!:f’ 1!
`froxii the
`[4 pl
`van’t Holt
`tl'le01'Y
`
`+‘°*”°
`-f-9,720
`} +n’460
`+9, 440
`
`1:11 141
`1
`"Cl.
`name
`17 —gucos1 e .............................................. _-
`;z_-d«g‘1tu1:‘c:3s5e-.l----,(.l..........................................
`me y -g ucos‘ e.............................................. .-
`B_d_g1uc°Se______ -:______________________________________________ -_
`methyl d-galactoside. .. . . ._ .
`_ . . . . . . . .. . . . . .. _ . . .. . . --
`E-d-gizlllatitgse.....--_.&........-
`--
`........................-
`....................... —-.
`--
`-82.130303! 8........... --
`-1119 Y
`fi_d_g3_]act0S6______________________________________________________ _ _
`-methyl d-mannoside............................................ --
`g'H,_mm0Se____._____________________________
`__
`_______________
`2Zfz‘3§{‘x’x’£e‘.’f€‘f‘?.‘ff1f‘:::::::::::::::::::::::::::::::_--_-_--::::::::::
`-methyl d-xyloside______________ __
`
`+10’ 000
`+11’ 440
`E-d-x%'}llo.<i'el___-_E__-EH______________
`4
`~me y -era in
`___________--
`+1o.72o
`+14.o1o
`,_,_mbim,_____f’___f______________________________________________
`I For the beta d-sugars the value given is -([£\I’]n-—[1VIln), but for thefi-loutabinose the expression is posi-
`tive, which arises from the nomenclature ol the a and 5 forms of the d- and t- sugars.
`'3 Hudson, J. Am. Chem. Soc., 47 p. 271; 1925.
`I3 The small letter 1 is used to designate the rotations in the pentose series.
`
`
`
`
`}
`}
`
`+9,93o
`+°»5°°
`
`+ 9'9”
`.
`-7-10,055
`+10’395
`+1‘). 505
`
`+9.995
`+1°»°"~“
`
` _v.-
`
`

`
`Isbclz]
`
`Optical Rotation and Rmg Structure in Sugar Group
`
`F’
`1001
`
`It is evident that the values calculated by the van’t Hoff theory
`agree more closely with the value (a,Me—-a.0H= 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 Hud.son’s equations 6 i CLO}; an.d b i am . The
`Value of b from the sugars may or may not equal the value of b
`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 isorot-ationz 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