Carbohydrate Stereochemistry Robert S. Shallenberger and Wanda J. Wienen New York State Agricultural Experiment Station. Cornell University, Geneva, NY 14456
The simple sugars possess multiple asymmetric carbon atoms, and many configurational isomers are therefore possible. In solution, they establish an equilibrium between special configurational forms and also between ring forms of different size. Those rings are also intrinsically chiral and may assume many different conformations. Finally, the glycosidic linkages of oligo- and polysaccharides are another source of conformational chirality. As progress in the develoDment of eeneral stereochemical nrinci~leshas been sienificantly inflienced by studies that iedto determinationzthe cwstalline and solution structures of the suears. the subiect o f carbohydrate stereochemistry is developed here in historical fashion. Stereochemistry, as an academic subject, began when Louis Pasteur (1, 2) discovered that the two crystalline forms of sodium ammonium tartrate present in a racemic mixture are alike in all respects except that one is the nonsuperposable mirror image structure of the other. In solution they also had equal hut opposite optical rotatory power. In svmmetrv terms. each c o m ~ o u n dlacks svmmetrv elements o?the'.sicond kind" and thkrefore is not ;uperposableon its mirror imaee structure. The classic analorv is that the left hand is the-nonsuperposable mirror imagystructure of the right hand. Proof of nonsuperposability is the fact that a glove made for the left hand cannot he fitted onto the right hand (3) unless i t is turned inside out, i.e., euerted. In the case of the sodium ammonium tartrates, one form rotates plane polarized light to the "right" (dextrorotation) and the other rotates the light to the "left" (levorotation). A third form, meso, is optically inert. The structure of the forms of the free acid in Fischer projection are CWH
i
7-
b
H O - CI
OH H
COOH
L-(+).ranarkncld
CWH
i
HO-YH H- C-OH I COOH
o-(-)-~anamc ncld
COOH
I
H - P O H H- C- OH I
COOH
Although the two structures are drawn as regular tetrahedra, and rendered nonsuperposable by differentially labeled apices, the concept that the theory intended toconvey is that the tetrahedra are geometrically irregular because the four different carbon substituents are of different size. In either case, the tetrahedra are nonsuperposahle. When a has higher atomicnumber than h, etc., (a > h > c > d), and the sequence a t the hottom of the tetrahedron is viewed with d "remote", the clockwise a to b to c sequence (1) will be the R(rectus) form and the counterclockwise sequence (2) will be the Skinister) form.
Meso Tanarlc Acid
I t is the L form of tartaric acid that is dextrorotatory (+). The D form is levorotatory (-). Because two forms of tartaric acid are optically active, Pasteur (2) was led to ask. "Are the atoms of the rieht acid the spirals of dextrogyrate helix, or piaced a t grouped the summits of an irreeular tetrahedron. or dis~osedto some particular (dissymmeGic) grouping or other? w e cannot answer these questions." In askinn the question, however, a basic principle governing stereochemishy wasestablished. Pasteur described that principle as molecular "dissymmetry". As the creation of n k w ~ r i n c hwords is the perog&ive of only the Acadbmie Fran~aise(41, "dissymmetry" does not usually appear in dictionaries. When i t does, i t is not defined in the sense that Pasteur used it, although it is used in that sense in the scientific literature. Webster's Third New International Dictionary (5) defines dissymmetry as "the ahsence or lack of svmmetrv". i.e.. as a svnonvm for asvmmetry. Therefore, when ~ L t d u rarticle i " ~ ~ s e a r e h e s " s ular DissymBtry MolBculaire des Produits Organiques Natur-
on
els" was translated, "dissym6try" became "asymmetry" throughout the text. Pasteur used the term dissymmetric in an apparent attempt to solve a conceptual problem encountered in descrihing the geometry of a helix. While being nonsuperposahle on its mirror image, a regular helix nevertheless has an axis of symmetry and-is not asymmetric. The modern term for the ideaof dissymmetry is chirality (4). Shortly thereafter van't Hoff ( 6 ) and LeBel (7) developed the idea of rhe"asymmetric"carbon atom toexplain why compounds that were optical antinodes were ~ossible.Van't Hoff deduced that when the tetrahedral carion atom was substituted with four difs a ferent erouos. with the bonds directed toward the a ~ i c e of tetrahedron, two mirror image forms are possible-that are not superposable, as shown below.
a
Because the four different substituents are not the same size, no two sides of the tetrahedron have the same length, nor do any of the four faces have the same area. Therefore, the apices can he circumscribed with a helix, as shown in Figure 1.Optical activity is believed to be due to differential interaction of chiral chromaphores with the rigbt- and lefthanded components of circularly polarized light (8). In recognition of the geometry described by the apices of an irregular tetrahedron van't Hoff (6) stated that "In the asymmetric carbon atom we have a condition which distinVolume 66
Number 1 January 1989
67
Emil Fischer (13) devised the scheme t o ascertain which structure could be assigned to natural (D-) glucose, and the scheme has been outlined by Hudson (14) and Percival(l5). Fischer found that glucose and mannose afforded the same phenylosazone (4). Therefore the configuration about carbon atoms 3-5 for glucose and mannose must be the same, whatever that may be, but the configuration about C-2 must be different.
Giucose or Mannose
-
HG-N.NH-C&
I I
HC-N-NH-C& HCI
OH
HC-OH
I
Hv-OH
Figure 1. A p i w of an ineguiar tetrahedron circumscribedwith a right-handed helical panern.
itself bv its helical arraneement." Desoite the scath-euishes ing criticism that statement in particular caused (91,stereochemistrv advanced raoidlv. based orimarilv on the idea of the "asymmetric" carbon atom. i he conceptualization of the asvmmetric carbon, rigidly defined as an asvmmetrically substituted carbon a t o h , reads to interesting contradictions (10). These resolve, however, either by application of systematic stereochemical considerations presented by Mislow and Siegel ( l l ) , or by simply making the criterion of nonsuperposability with the mirror image structure an absolute requirement, as van't Hoff subsequently did (4). The latter criterion is eauallv to the tartaric acids to . - a~olicahle -. explain why the L and D compounds are optically active and the meso form is not. The L-(+) c o m ~ o u n dhas two asvmmetric carbon atoms with the R configuration, i.e., it is (2R,3R-tartaric acid. I t is not superposable on itsmirror image, D-(-)-tartaric acid, i.e., (2S,3S)-tartaric acid. mesoTartaric acid or (2R,3S)-tartaric acid is optically inert hecause of internal optical compensation. Conflguratlon of the Sugars When a compound has only one asymmetric carbon atom, the confieurational isomers are enantiomers. If thev have more than one asymmetric carbon atom, the potential for diasterisomers, i.e., configurational isomers that are not enantiomers (12) arises. meso-Tartartic acid is a diasterioisomer of both D- and L-tartaric acid. The soundness of van't Hoff and Le Bel's idea gained support in that its application led to an explanation for the occurrence of many different sugars, all with the molecular formula C6H1206. AS any compound with n asymmetric carbon atoms can have 2" configurational isomers, the minimum number of stereoisomers for the straight chain form of the formula C&206 (3). whereby carbon atoms 2-5 are asymmetric, must be Z40r 16. Eight of the sugars must then be diastereoisomers belonging to one enantiomeric class, and eight must belong t o a second enantiomeric class.
Hr
('I (2)
C'H.OH
I
T o derive their relative configuration, Fischer relied on the presence or absence of symmetry, and therefore the absence or presence of optical activity that is displayed by acyclic sugar acids prepared by oxidation or acyclic sugar alcohols prepared by reduction. The approach employed was t o deduce whether or not the acids/alcohols possessed a mirror plane of symmetry. The oxidation of mannose and glucose produced dibasic acids (either 5 or 6 below). both of which are optically active. Neither possesses a mirror plane of symmetry. Dibasic acids (or alcohols) with structures 7 and 8are optically inactive because they do possess a mirror plane of symmetry. COOH
COOH
I
mF-OH
H O - C H
I
bC'-OH
I tLC.-OH I
COOH
5
H-C-H
I I
HO-0-H
I
H--C'-OH
I bC'-OH I
COOH
6
COOH
I
COOH
I
b O O H
I I LC'-OH I
L C O H
"F"OH COOH
7
H O-? ' , H O - C H
I I C.I
HO-C'-H
*
OH
COOH
8
The significance of this procedure is not always easily grasped hut has a t its roots the fact that, when a mirror olane bisects a symmetrical object, such as a molecule of wate;, the reflected image in the mirror is identical with the half of the molecule being reflected and is superposahle upon it. The reflection then carries the molecule "back into itself'. When an asymmetric carbon atom is reflected in a mirror, the reflected image is that of an asymmetric carbon atom with o ~ o o s i t e"handedness" in the same sense that the reflected irkage of the right hand is the general structure of the left hand, and thev are not suoeroosahle. This can be visualized as the reflected priority se&nce of the asymmetric tetrahedral carbon atom being reversed, or as the formation of a left-handed spiral by reflection of a right-handed spiral. Thus, if the two starred hydroxyl groups in 5 are designated (R,R) then a mirror plane bisecting the molecule creates an (S,S) image of them. The R,R configuration and its reflection, which is S,S, is therefore symmetrical because i t is bilaterally symmetric1. This is also the case for structures 7 and 8 and for meso-tartaric acid. On the other hand. while the groups to be reflected in 5 are (RJ?),the other half of the molecule isactuallv rS.R). Thus. it is not hilaterallv-svmmet. ric, hut chiral inscad A d optichly active. In practice the procedure can be exemplified using an optically active pentose, trivially known as D-arabinose, but
' The combinatfon of " i e n and "right", as in the human form. 68
Journal of Chemical Education
with an unknown relative confiauration a t C-3 (9). D-Arabinose yields an optically active dihasic acid upon oxidation. Arbitrarilv writing OH-4 to the rizht, the OH group at C 2 must be written to the left, as thedihasic acid wouid otherwise be optically inert, regardless of configuration at C-3. The highest numhered asymmetric carbon atom OH group is written to the right to establish the relative configuration about that chiral center which distineuishes the D-series of sugars from theLseriesof sugars. u p & cyanohydrin synthesis and suhseauent oxidation of the two resulting hexoses. both dibasic acids obtained are optically active. yhis result establishes that OH-3 of the pentose must be written to the right in order to yield the two active compounds 5 and 6. If it were on the left, one of the two acids produced would he inactive (10) and 'the other (11) would be optically active. Thus, the relative configurational stereochemistry of Darahinose (9) is established as (2S,3R,4R)-tetrahydroxypentanal. COOH CHO
I
Hby-H
Cyamhydnnsynlhsrisondoxl.
'-y7 d.tiO"VlhOHd.tOthOlBh.
H- C- OH
I
-
*-OH
I
70" HO-C-H I
I
HbC-H I
+
IHo)-p(HJ kc-OH
I
10
(rnactlve)
b
G
14
O
I
H-C-OH H
CI
I
I
I.
H-C-OH
I
H-C-OH
I
I
11 I A F I I V ~ I
Continued study along these lines led to formulation of the configuration of the entire families of D- and L-aldehydo- and keto-hexoses. The relative configurations of Dand L-glucose proved to he structures 12 and 13. The arhitrary assignment for the highest numbered asymmetric carbon obtained by writing the OH group "to the right" for D-arabinose and D-glucose is now known (16) to he absolute.
13 HO-+H
H-
H-C-OH I COOH
COOH
CHpH 9
H O - ID H
three unsuhstituted "D-glucoses" with specific rotations of about +llZO,+5ZQ,and +lgO. Armstrong (23) then demonstrated t h t the structure of the two methyl glucosides is directly related to two of Tanret's glucoses, i.e., those with rotations of + l l Z O and +lgO. Aldoses or ketoses form rine structures bv virtue of intramolecular hemiacetal or hemrketal formati& through reactionof thecarbonvl . erouo - . with a hvdroxvlerou~. - - . Collev (24) proposed that ring closure occurs between positions one and two, in order to explain the sluggish aldehyde properties of glucose, hut Tollens (19) proposed either the (1,4) oxide ring (14) or a (1,6) oxide ring (15).
I
HOIC-H
By application of configurational nomenclature specification procedures (17), acyclic D-glucose is (2R,3S,4R,5R)pentahydroxyhexanal. The specification for those asymmetric carbon atoms for a six-membered ring form of D-glucose, however, is (2R.3S.4S.5R) (18). Refinements in ordering the reference priority for specification of sugar stereochemical structure using the H,Sconvention ( 1 7 ) may therefore be in order. Sugar Anomerlc Forms The occurrence of sugar anomers is a special case of confieurational isomerism. The Fischer elucidation of suear c&figurational isomers was confounded by the suspicyon (19) that the sugars have a hemiacetal tvDe of rine structure. If so, then carbin atom no. 1is asym&tric, a n i instead of one structure for the configuration of D-glucose, there must he two. When Fischer (20) reacted acidic methanol with glucose, he isolated a methyl glucoside with a specific rotationof +157O. Shortly thereafter AlherdavanEkenstein (21) found a second methyl glucoside with a specific rotation of -34". He named the compound obtained by Fischer (methyl) a-glucoside and the second (methyl) P-glucoside. Tanret (22) subsequently found there are at least two and perhaps
The stereochemical problem that arose next was "Should the OH-1 group for the usual form of D-glucose, and corresponding to methyl a-D-glucoside,be written t o the 'right'or to the 'left'?" The problem was solved by BBeseken (25) employing the knowledge that cis vicinal OH groups on fivemembered rings are sterically disposed to react with the borate ion to increase the acidity (and conseauently the conductivity) of the reaction mixture. Trans iicinai OH groups are inert in this respect. Boeseken found that i t is the &a1 form of D-glucose, with a specific rotation of +112" that reacts with boric acid, and as that form must have the cis configuration between OH-1 and OH-2, i t is assigned structure 14 and called a-D-glucose. 8-D-Glucose than has the trans confieuration between OH-1 and OH-2. These configurational isomers are called anomers, i.e., "upper" epimers. Therefore. instead of eieht confieurational isomers belonging to t h e n series, there are 16. '?he distinguishing feature of an a-D-anomer is that the anomeric carbon atom has the same configuration as the reference carbon atom. The 8-D-anomer then has opposite configuration. The finding that D-glucose can have two anomeric forms served as the solution to a number of heretofore unexplainable observations. Foremost among them was the fact that the disaccharide of commerce (sucrose) had a constant specific rotation of +66.5". while that of the usual form of glucose changed from aninitialvalue of about +112" to final value of +52.5'. The significance of the phenomenon (mutarotation) was not known. Dubrunfaut (26) suspected early on (1846) that mutarotation was due to an eauilibrium between different molecular species (and thus there might he more than one n-alucose),but Fischer believed it to be due to the formatioi of glucose hydrates. Lowry (8)finally showed that mutarotation (a term that he coined) is due to the formation of an eauilibrium between the a-D- and 8-Dglucose forms and that Tanret's third form, with a spe'cific rotation of +52'. corres~ondsto an eauilibrium between them. Starting with the &ual crystalline form (+llZO),the mutarotation direction was "downward" to an equilihrium valueof 752. Whenstarting with thecrystalline form ofB-Dglucose (+lgO),mutarotation was "upward" to the same equilibrium specific rotation. At equilihrium, it was then calculated (Hudson, 27) that the position o i the eauilibrium is about 64% 8- and 36% a-D-glucose. Another stereochemical problem solved by the finding that D-glucose had two anomeric forms was the observation Volume 66
Number 1 January 1989
69
that cellulose and starch, although obviously different and economically important polysaccharides, afforded only Dglucose upon acid hydrolysis. Because cellulose is a polymer with8-D-glucoseas the repeatingunit and the repeating unit of starch is a-D-glucose, their properties differ. Ring Forms of the Sugars
The early conclusion that the usual cyclic forms of the sugars were five-membered, as in 14, is attributed mainly to application of the Baeyer strain theory. I t also followed because the y-lactones of the sugar acids were known to have a five-membered ring structure. As a consequence, it required the accumulation of massive evidence through methylation (2% optical rotation (29), bromine oxidation (30). and other studies to establish that the usual form of the free sugars (pentoses, hexoses) was that of a six-membered ring, and not five-membered. An account of an interesting disagreement on this subject is given by Perlin (31) and Isbell (32). Nevertheless, once the six-membered nature of the sugar ring became established as the usual structure, methods needed to be derived to indicate or portray it as accurately as possible. The Fischer-Tollens structure for a-Dglucose (16) accurately shows the configuration ahout each asymmetric carbon atom, hut the single covalent ether honds that "close" the ring are disproportionate.
Structure 17 is not meant to bear any resemblance to 16, and has special connotation. I t was devised by Drew and Haworth (33), and the extracyclic hydroxymethylene group is printed horizonally to convey the idea that the molecule is to be viewed in perspective with C-3"near", and the ring oxygen atom "remote", as shown in 18. Structure 19 is a planar representation of 18, hut the ring is drawn in the same plane as that of the paper. Solid single covalent honds in 19 indicate that the carbon atom ring suhstituents are perpendicular to the ring and projected toward the viewer, i.e., they are "above" the plane for the ring. Dotted single covalent bonds project back through the paper and are "below" the plane for the ring. In addition, this first Haworth-type structure for D-glucose to appear in print had a carbon atom numbering sequence that is counterclockwise. The sugar is, nevertheless, D-glucose.
mensional planar objects with the plane descrihed by the ring oriented perpendicular to the plane of the paper. The front edge of the drawing was shaded, as in 20 and 21 to emphasize this new convention. In addition, the carbon atom numbering sequence convention used is now clockwise, and carbon atom suhstituents "above" the plane for the ring are now directed toward the top of the paper on which they are drawn, and those "below" are directed toward the hottom of the paper. By appending the suffix "-ose" to the generalpyran- and furan-like nature of the sugar rings, compound 20 is now generically descrihed as a-D-glucopyranose and compound 21 is a-D-glucofuranose.
Haworth (34) structures 20 and 21 are convenient for depicting the structure of sugars in oligo- and polysaccharides, and the aforementioned primary structures of starch and cellulose are 22 and 23, respectively.
The repeating monosaccharide unit in 22 is a-D-glucopyranose, and the repeating oligosaccharide (disaccharide) unit is a-D-maltose 14-0-a-D-glucopyranosyl-a-D-glucopyranose). The repeating monosaccharide unit in 23 is 0-D-glucopyranose, and the repeating disaccharide unit is 8-D-cellohiose(40-8-D-glucopyranosyl-m-glucopyranose).
. H-+OH
Subsequently, and in contrast to the significance of structure 19, the five- and six-membered ring structures for a-Dglucose came to he depicted by Haworth (34) as three-di70
Journal of Chemical Education
trace
trace Figure 2. Tautomeric forms of wlucoae in solution.
trace
At this stage in the development of sugar stereochemistry it was recognized that sugars in solution possess a numher of tautomeric forms. One of them is an acyclic structure, as the sugars showed some of the properties of an unsubstituted carbonvl comoound. Different rine forms are Dossihle. and while the six-membered pyranose form is favored for most hexoses and Dentoses. there are occasions when sienificant amounts of the five-membered furanose forms are encountered. The ao~roximatediastereoisomeric com~ositionof a water soluti& of D-glucose is described in ~ i g u i 2. e As shown for 22 and 23, and also in Figure 2, it is common practice not to shade the front edge of the pyranose and furanose rings to indicate that the rings are to he viewed as being in perspective and perpendicular to the plane of the paper. The convention that the ring is perpendicular to the oaoer . . is then imolied. . . hut often foreotten. If it is not foreotten, the Haworth structure for n-D-glucopyranose can he oriented in twelve different wavs without losine its identitv. Two methods of depicting the knantiomer of ckglucop$anose, i.e. u-L-glucopyranose, are given in 24 and 25.
Structure 24 is formed from 20 either by chemically transposing the configuration ahout each asymmetric carhon atom or hy conceptually placing 20 upon a mirror and drawing the reflected structure. Structure 25 is ohtained from 20 by placing the mirror to the right of the anomeric carhon atom. In either case, the compound is cr-L-glucopyranose, either one of which can he oriented in 12 different ways by placing different hexagonal sides of the ring on the plane of the paper. Conformatlonal Isomers When the pyranose and furanose forms of sugars and the method for depicting them was proposed, Haworth (34) mentioned that the rings should not, in the final analysis, be considered as planar objects. The angle between carhon-tocarbon bonds is 109"28', and the sugar ring must be puckered. Puckerine or skewine a reeular and svmmetrical " eeometric form imparts another element of dissymmetry (chiralitv) to he taken into account. However. Haworth felt the subject should remain for future generations of stereochemists to exdore, . . as those considerations would oDen UD "a large field of inquiry into the conformation of groups as distinct from structure and confinuration." Thus, the term "conformation" was introduced into the field of stereoche-
-
u
protons, is formed from 26, with unlabeled protons, by merely turning the molecule over. At ambient solution temperature. 26 and 27 are also in r a ~ i deouilibrium. and one is forked from the other through'ring ;version. he result of rine eversion. throueh rotation about sinele covalent bonds. is &at all h;drogenatoms that are axiaiy disposed in one conformation become equatorially disposed in the second, and vice versa. With labeled protons the compounds are not superposable and are, in this sense, enantiomers. In addition to the two chair forms for cyclohexane, hoatlike structures are possible, as in 28 and 29.
The possibility for various chair and boat conformational forms for heterocvclic suear rine structures also exists (37. 38), and two chaiiand six;'hasic;' hoat forms are recognLed (38). alonn with a varietv of "twist" hoat forms (39). Unlike the case for "enantiom&ism" in cyclohexane chair structures that results from conceptual differential laheline of protons, the two possible chails for a given sugar struciure are in fact "enantiomeric". Ring carbon atoms of heterocyclic sugar rings are electronically different because each of the substituent hydroxyl groups is electronically nonequivalent. The rine substituent ~ r o t o n sof the chair forms of hand, electronically equal. cyclohexane are, on the Therefore heterocvclic ~uckeredrine forms of a suear are chiral while the chair stiucture of cydohexane is notProof of sugar heterocyclic ring chirality is straightforward (40) and affords opportunity to introduce fundamental "principles of chirality" and "chiral overations" for comuariion and contrast to-symmetry prinkples and operatibns. Because the planar hexagons 30 and 31 are differentially labeled in clockwise and counterclockwise fashion, respectively, they are not superposable in the plane of the paper on which they are constructed.
otter
-
....-
mid," ".>.
The initial principles of sugar conformational analyses are derived from Sachse-Mohr type of considerations (35.36) as applied to cyclohexane stereochemistry. Compuunds 26 and 27,
are the two energetically favored chair forms of cyclohexane, and they are identical when the hydrogen atoms are unlabeled. They are identical in the sense that 27, withunlabeled
Differential labeling of a regular (symmetrical) geometric object is therefore a chiral operation (cf. the case for a regular tetrahedron and for differentially labeled cyclohexane protons). When cut from the paper, 30 and 31 become templates, and each is now symmetrical because they are superposable through a simple rotation operation. In other words, the chirality that prevailed in a two-dimensional realm is extinguished in three dimensions2. If label 0 for each template is next folded toward the operator along the dotted line between labels 1and 5, and label 3 is folded in the opposite direction, the templates are again not superposable due to The fact that the chirality displayed by an object in a given dimension disappears In the next highest dimensional continum is a unique feature of the concept of chirality and readily distinguishes it from the notion of symmetry. It Is probably because of this fact that concepts known as "prochiraiity" or "pseudochirality" have been recognized. In the final analysis, these ideas are a manifestation of twodimenslonal chirality. Volume 66
Number 1 January 1989
71
the fact that they arenot only differentially labeled, but they are also puckered. Therefore, puckering, (skewing, warping, etc.) is also a chiral operation. The puckered and differentially laheled template serves as the model for the chair forms of heterocyclic sugar rings to demonstrate the fact that they too are indeed chiral. The templates can be rendered superposable merely by everting one of them, i.e., by folding labels 0 and 3 in the opposite direction. Current symbols to describe the chiral nature of sugar heterocyclic rings identify the carbon atom(s) that are skewed from the "average" plane for the ring, and also the direction in which they are skewed. The favored mirrorimage conformations for the sugars are the chair 4C1(32) and 'C1 (33) forms.
The italic symbol "C" indicates a chair conformation in which carbon atoms number 1 and 4 are displaced either "upward" or "downward" from the average plane for the ring described by carbon atoms 2, 3, and 5 and the ring oxygen atom. When originally introduced (38), structure 32 was assigned the symbol C1 and 33 the mirror image symbol 1C. As the C1 symbol was frequently confused with specification of carbon atom number one (C-l), and superscripts and subscripts are needed to distinguish various skewed boat and furanoid envelooe and twist conformations. the use of suoerscripts and s ~ h ~ c r i pfor t s specifying all su&r conformations was orooosed (3%. Thus, if the favored conformation for a given sugar is either 32 o; 33, then the favored conformation for its enantiomer is the mirror-image conformation. o s4C1 e conforIn addition, everting ~ - ~ - g l u c o ~in~the mation (34) results in the mirror-image 1C4 conformation (35), and the two are in equilibrium in solution.
In everting 34 to 35 all equatorially disposed hydroxyl groups transpose t o an axial disposition. Compound 35 is as the confieuration about each still B-D-eluco~vranose. , asymmetric cai6on atom has not beenktered. Therefore 35 is the conformational diastereoisomer of 343. In B-L-glucose. while the favored conformation is 'C4, and although ali asymmetric carbon atoms have opposite configuration, all ring substituents bear the same axiallequatorial disposition as found for the favored conformation of the D-sugar (34), e.g., either 36 or 37, for comparison with the Haworth ring structures 24 and 25.
-
A given conformational structure for the sugars can also be written 12 different wavs without losinr! the identitv of the sugar. Application of general principles of conformational analysis (38, 41), or application of free energy calculations (42) leads to a decision regarding the relative stability of a multitude of sugar conformational forms. Empirical quantification of staggered pairwise arrangements of ring suhstituent oxygen atoms leads to estimates of optical roiatory power from structure and vice versa (4346). Structure 34 is the most favored configurational and conformational structure for all of the D-aldohexose sugars, while 35 is the least favored. This is because the difference in energy between the two structures is related to the number of axial hydroxyl groups. Other hexoses, which can be neither all equational nor all axial, are intermediate in energy. I t therefore follows that the position of the equilibrium shown for structures 34 and 35, in contrast to the 1:l equilibrium position between equivalent cyclohexane structures 26 and 27, is shifted almost complekly to the left. Furthermore, it can be calculated (43,44) that 34 is dextrorotatory and that 35 is levorotatorv. Confirmation of the calculated levorotatorv nature of 35 rs found in the observation that 38 (levoglucosk) is levorotatory.
In concluding this discussion, it needs to be mentioned that there is yet a third center of chirality in the structure of the carbohydrates. The glycosidic linkage between the monomeric units of the disaccharides imoarts a third element of dissymmetry to the compound (47):It is due to preferred angles (4 and i p ) , as in 39, due to rotation of monomeric units, that lead to a favored glycosidic linkage conformation. The favored conformation is usuallv gauche (staa~ered).The glvcosidic linkage conformation &o contributes to the op&al rotatory properties of oligosaccharides.
Literature Cited 1. Psstcur, L.Ann. Chim. Phys. 1848.24.442.
2, PaaW~r,I.Re8earche on the Mobculor A~ymmafryof NoLuml Organic Roductr: Al~mbicClubReprintNo.14.ThcAlembieClub.Ediibbbbgh;UniiiiityofChicago Pmac Chicago. 1915. 3. Elie1,E.L.J. Chem.Edue. 1964,41,73. 4. O'Loane. J. K. Chom. Re". 1980,80,41. 5. Webards Third New Inlemotionol Dictionow; Merriam Webatu: Springfield, MA,
.*-" m,o.
Is) Arch near. l874.9,445: lb) Die Logerung der Atom. in Raump; Vieweg: Brsunsehweig, 1877. 7. LeBel, J. A. Bull. Soe. Chim. R.1874,222,337. 8. Mason. S. F. Molecular Optical Acliuity ond tho C h i d Diacn'minotiou; Cambridge Uniu.: London, 1982. 9. Riddoll, F.G.; Robinson, M. J. T. Tetrohadron 1974.30, 2 W 1 Kdbe, H. J. Pmkt. Chem. 1877.15.473. 10. Jaeger, F. M. Oplieol Activity ond High Tempemfurs Memummanfs; McGraw-Hil: Nelv York, 1930; pp40-42. 8. Vsn't Haff, J. H.
As- a is deflned 112) - diastereoisomer ~ ~ . . as an isomer that is not an enantiomer, configurationaland conformal onal isomers of the same sugar are aiastereoisomers,an0 pyranose and f~ranose ring forms01 the same sugar are a so diastereolsomers. ~
36
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Mialaw, K.: Siegel, J. J. Am. Chem. Soc. 1984,106,3319. Eliel, E. L. J. Chem. Educ. 1971.48.163. Fiacher, E. Be,. 1891.24.1836. Hudson.C.S. J. Chem.Edur. 194l,18,853. ~ Percival, E. G. V. Sfrvcfurol Corbohydmfe Chemistry: Miller: London. 1 9 6 2 ; 24. J.Nolure 1951,168,271. Bijvoet, J.M.;Peerdcman,A. F.;-Rommell,A. Cshn, R.8.;Ingold, C.: Prelg, V. Angem. Cham. I n t . Ed. I965,5,385. Bentley. R. Molecular Asymmetry inBiology; Academic: New York. 1965: p 56. Tollem, B. Ber. 1883,16,921. Fischer. E. Bor. 1893,26,24W. Alberdsvsn Ekenstein. W. Roe. T m u . Chim. 1894,13.183. Tanref C. Compt. R o d . 18'35,120,1050. Armstrag, E. F. J. Chem Soc. lM3,83,1305. Co1ley.A. Compf.Rond. 1870.70.403. Rbseken. J. Adu. Corbohydr. Chsm. 1919.4.189. Dubmnfaut,A.-P. Compt.Rend. 1846.23,38. Hudson.C.S. J Am. Chem.Soc. 1909.31.66. Hirst,E. L.,Purves,C. B. J. Chem.Soe. 1923,123,350.
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Charlfan, W.:Hawiorth,W.N.;Pcat,S.J.Chem.Sw. 1926.89. Isbell, H. S.: Hudson, C. S.J. Rea. NoH. Bur. Stand. 1932.8.327, Per1in.A. S. Can. J.Chom. 1W6,44,539. IshlI, H. S. Chem. Soc. Re". 1974.3.1. Drew, H. D. K.; Haworth, N. J. Chem. Soc. 1926,2303. Hswodh, W. N. The Comtitution of tho Sugars; Amold;Landon Sschae, H. Ber. L890.23,1363. Mohr, E. J. Plait. Chem 1918.98.315. Hassel.O.;Ottar,B. Aefo Cham.Seond. 1947,1.929. Reews. R. E. J. Am. Chom. Soe. 1949.71,215. Scwarz,J.C.P.J. Chem.Soc.Chpm. Comm L973.505. Shsllenberger, R.S.: Wmlstad, R.E.; Kerahner. L. E. J. Cham.E< Kelley, R.B. Con. J. Chem. 1957,35,149. Anwall. S. J.Ausf. J. Cham. 1368,21,2737. Whiffen. D. H.Chem.lnd. (London) I954 964. Brewster, J . H. J.Am. Chem. Soc. 1953.81.5483. Lomieur,R. U.;Martin, J.C. Corbohydr.Rea. 1910,13,139. Angyal. S. J. Corbohydr Re8.1979.77.37. Rees, D. A. J. Cham. Soc. B 1970,877.
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January 1989
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