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System for Classification of Structurally Related Carbohydrates 1

System for Classification of Structurally Related Carbohydrates 1

Journal of Research of the National Bureau of Standards Vol. 57, No.3, September 1956 Research Paper 2707 System for Classification of Structurally Related

Carbohydrates 1 Horace S. Isbell

A system is presented fo r t he classifi cation of structura lly a nd confi gurationally related . Each substance is assigned a code number t hat defines t he s tructure a nd configuration. By inspection of t he code numbers, or by a punched-card technique, groups of structurally related derivatives can be selected read il y from a heterogeneous collection . The structures, configurations, and conformations of a nd der ivatives are di scussed, and classifications are made on t he basis of a few fundamental structures. Certain ambiguous and objectionable features in the classifi cation of p y ranose ring conformations in t he Cl and I C categori es of Reeves are pointed out. In this pa per, C I denotes t he chair confor mat ion in both the D and the L aldohexose se1'ies in which t he reference group attached to carbon 5 of t he ring is in the equatorial position. Sim ilarly, C2 denotes t he chaiT con formation in bot h seri es in which the reference group attached to carbon 5 of t he ring is in t he axial position. and are classifi ed like ; and t agatose lik e ; a nd like ; and and like . Because the designations al'C indcpendent of t he D or L series, they avoid t he erro­ neo us classifi cation of cnant iomol'phs in diff erent conformations. 1. Introduction quent paragraphs the structural elements involved in classification will be considered in order, and During thc past sevcral ycars the infrared absorp­ directions will be given for assigning code numbers. tion spectra of a large group of carbohydrate de­ rivatives have been m easured at the Bureau with 2 . Components of the Code Number the object of providing reference spectra and data for structurall y related materials. A classification 2.1. Type of Carbohydra te system was devised to show the structure and con­ figuration of the compounds by means of numbers The first digit in the code number divides the suitable for coding and separating by punched-card carbohydrates into groups of increasing complexity: techniques. Although the system was developed 1 signifies a ; 2, a disa,ccharide; 3, an primarily for comparing infrared abso rption spectra, ; 4, a composed of one it can be used for classifying structurally related type of unit; and 5, a polysaccharide co mposed of a carbohydrates for any purpose . variety of units. Substances in types 1 to 4 are The code nwnbers arc assigned by means of a key given definitive code numbers but no attempt is outlined in tables 1 and 2. A decimal poillt is in­ made to classify substances in 5, beyond codillg the serted after the second digit to separate fi gures that structural units present. provide broad generic classification from those that show definite structure: For example, a-D-glu­ 2.2. Major Substituent copyranose is given the code number 10.2110. Reading from left to right, 1 shows that the sub­ The second digit is assigned to show substitution stance is a monosaccharide; 0, that the hydroxyl on the polyol structure. When half or more of the groups are predominantly unsubstituted; 2, that it hydroxyls are free, the classification number is 0; has a primary 6-carbon structure; 1, that it has the when more than half of the hydroxyls ar c substituted glucose configuration ; 1, that it has a C1 pyranose the number corresponds to the substituent present in ring with an axial glycosidic group, and 0 that the predominating amount. If two classifications are glycosidic hydroxyl is not substituted. The code possible, the one with the lower number is used. numbers for all a-D-glucopyranose structures will have the .211 sequen ce . Each structural grouping 2.3. Carbon Skeleton has a, characteristic sequence of numbers. Hence The first digit to the right of the decimal point by inspection of the numbers, or by punched-card defines the skeleton of the fundamental carbon chain. technique, groups of structurally and confi guration­ Alcohols, , aldonic acids, uronic acids, etc., are ally related carbohydrate derivatives can be readily classified as primary; and related compounds selected. The classifications arc not intended for as secondary. Cyclitols and higher are in­ general nomellclature [md no changes are proposed cluded in a miscellaneous group, 9. The aldo­ in the rules for naming carbohydrates. In su bse- are placed in t wo groups designated as 7a

1 The work reported in this pllblication was sponsored by tbc Office or Naval and 7b. Substances in the 7a group have like con­ Rewarch as part ora program on the investigation of the structure, configuration, figurations for the two configurational units given in and ring conformation of the sugars and thei,· derivatives by infrared absorption measurements (NRO 552081. The classifi cation system presented here has the conventional ACS name [1]; 2 those in the 7b been used to classify th~ infrared spectra of about 200 carbohydrate derivatives. The spectra and reference numbers will appear in forthcoming publications. 2 Figures in brackets indicate the li terature references at the end of this paper. 171 TABLE 1. Classification key for code nwnbers

Code I!. 'J'ypeofcarbohydratc 2. Major substituent 3. Carbon skeleton 4. Configuration 5. Characteristic unit 6. Substituen t ou main functional gro up ·

o Not substituted < 5 primary R acemic Anomeric mixture Not substituted. 1 Monosaccharide M ethylated 5 primary glueo ","Pyranose Cl 2 nisaccharide Acetylated 6 primary manno e-Pyranose C 1 3 Oligosaccharide Nitrated 7a primary gala!:lo a-Pyranose C2 4 P olysaccharide 7b primary tala e-Pyranose C 2 [See table 2 fo)' list of (s imple) substituents.] Polysaccharide < 5 secondary ida Ot her pyranose (complex) (j t, secondary g1l10 Furanose 7 6 secondary alt ro GIycitol 8 7 secondary allo Aldehydo or keto deri v­ ative. Misce ll a n~ o us M iscellaneous Miscellaneous Miscellaneous Acid derivative

• Asterisk is used to indicate linkage in higher saccharides.

TABLE 2. Numbers for substituent groups and auxiliary stncetlues

Code Substituent group Code Substituent gro up Code Substituent group Code A uxiliary structure --- I 0 None. 10 OH grou p. 30 Miscellaneous estel's. 50 Nitrogen dcr ivati\"cs. 70 Carboxylic acid. 11 O-Methyl. 31 PllOsphate. 51 Amino. 71 Carboxylic ester. 12 O-Ethyl. 32 N itrate. 52 Acetamido. 72 Carboxylic 'Y-Iactonc. 13 O-CycIO]lCXY I. 33 Sulfate. 53 N-Glycosy!. 73 Carboxylic Ii-lactone. 14 O-Benzyl. 34 O-Tosyl. 54 Phenylhydrazine df'riyu- 74 Carboxylic amide. tive. 15 O-Phenyl. 35 O-Mesyl. 55 Oxime. 75 Carboxylic salt. 16 O-'rrityl. 36 5fi 76 Oxo derivative. 17 37 57 77 18 Aldehydro!. 38 58 78 19 39 .19 79 20 Carboxylic ester. 40 Lin kages othN than 0 or N . 60 Cycli c derivati\'(ls. 80 D eoxy. 21 O-Acel.yl. 41 Fluoride. 61 Isopropylidene. 81 Deoxyam ino. 22 O-Brnzo)'!. 42 Chloride. 62 Benzylidene. 82 D roxyacetamiclo. 23 43 B romide. 63 I-Methoxycthylidenc. 24 44 Iodide. {j4 I-Mcthoxybenzylidenc. . 25 45 Mercaptal. 65 Ethylene oxide. . 26 46 66 Butylene oxide. 27 47 (;7 Amylene oxide. 97 Organi c solven t of crystalliza- tion . 28 48 68 B exy lene oxide. 98 Salt of crystallization. 29 49 69 99 'Vater :)f crystallization. group have unlike configurations. Thus a D­ TABLE 3. Classification of configuration glycero- D- gluco-aldoheptose or an L-glycero-L-gluco ­ aldoheptose is classified 7a, whereas a D-glycero-L­ Ald otetrose Aldopen lose Keto Related gluco-aldoheptose or an L-glycero-D-gluco-aldoheptose aldohexoses is classified 7b. The first pair of compounds as '" '0'" '0" '0" '"0 Configuration 0 Configuration 0 Configuration 0 Configuration well as the second pair are enantiomorphic, and for -0 ----- 0 0 0 evaluation of infrared absorption, do not require 2 . 1 Xylose. 1 So rbose. 1 Glucose. separate code numbers. 2 . 2 L yxose. 2 . 2 Mannose. 3 Arabinose . 3 Fructose. 3 Galactose. 4 R ibose . 4 Psicose. 4 Talose. 5 . 6 . 2.4. Configuration 7 . 8 . The second digit to the right of the decimal signi­ I fies the configuration of the main structural unit, Configurations listed in table 1 are assigned numbers 2.5. Structure 1 to 8 according t o the scheme outlined in table 3_ The digit third to the right of the decimal repre­ No distinction is made between D and L modifica­ sents the characteristic structure of the substance_ tions because enantiomorphic substances give like Products containing anomeric forms in equilibrium, absorption. Racemic substances are grouped under as, for example, amOl'phous sugars and materials not 0, and compounds not covered elsewhere are classified subject to specific classification, are represented by under 9. Because the and ketohexoses 0 ; pyranose and furanose structures by 1 to 6; have one less asymmetric carbon than the aldo­ glycitols by 7 ; open-chain and k etone , each can be considered to be related to two derivatives by 8; and aldonic acids by.9 r egardless of aldohexoses that differ in the configuration of the whether they are present as the aCId, salt, ester , terminal asymmetric carbon. On the basis of sim­ amide, or lactone. Assignment of code numbers for ilarity in properties, the pentoses and ketohexoses the pYl'anose and furanose derivatives requires are classified under configurations 1 to 4 rather than review of some problems of nomenclature and ideas 5 to 8 [3]. of configurationally related carbohydrates (see sec- 172 tion 4). Briefly, however, are classified substitution, the next number defines the substituent. according to ring conformation and the position of Several substituents can be listed consecutively. the glycosidic group with respect to the plane of the ring. Pyranoses a and e have, respectively, axial and equatorial glycosidic groups.3 All furanose Examples Code derivatives are represented by 6. 2.6. Main Functional Group 2,3,4, 6-Tetra-0-acety l-a-D-gl ucose_ 12.2110 3-0-Methyl-a-D-glucopyranose ___ 10.2110(3) 11 2,3,4-Tri-O-acetyl-a-])-glucosc __ __ The figures occu !lying the fourth and fifth positions 12.2110(6) 10 2, 3ose-Iso ______propyl idene-/'l-_D-l______yxopyran- to the right of the decimal in the code number show 10.1220(2,3) 61 the character of the main functional group, usually M ethyl /'l- D-galactopyranoside G- the glycosidic group. Because there are more than nitrate ______10.23211 (6)32 2- 0 - M eth y 1- 6- 0- t1' i ty I-a-D- 10 common substituents, two spaces are allowed for glu copyranose ______] 0.2110(2) 11 (6) 16 this structural feature. The numbers given in table 2 are used to describe substitution not only of the main functional group, but also of other parts of Auxiliary or additional structures are treated like the molecule, as described in section 3. The substituents. The main functional group is con­ numbering system can be readjusted to fit any sidered first, and the second (auxiliary structure) is collection of carbohydrate derivatives. shown by suitable numbers following its position in The numbers representing the substituent groups parentheses. are used with structures of diverse type. Thus a methyl group when used in conjunction with struc­ tures 1 to 6 (column 5 of table 1) represents a Examples Code ; with 7, an ; with 8, an acetal; and with 9, an ester. Application of the system can be 2-0xo-0-glll coni c acid ______10.2190(2)76 seen from the examples that follow : a-o-GllI cofli ran uronO-'Y- lactoIlP ______]0.2160(6) 72 Salt of a-])-glucopy ranurollie acid ____ 10.211 0 (6) 75 E ster of methy l a-D-glllcopy ra nlironidc_ 10.2111 J (6) 71 Examplcs Codc 2-Deoxy-2-am ino-a-D-gl \Icop yranose __ 10.2110(2)8 l 6-DcoxY-L-ma n nopyranosc ______10.2210(6)80

Methyl a-D-xylopyranosidc ______10.11] I I Methyl a-D-glucopyranosidc ______10.2]] J J Structures in the main functional group and a-D-G lu copyra nosc I-acctate ______10.21121 similar structures in auxiliary groups do not always Methyl D-glu conatc ______10.2J 911 a-O- iVIannopyranosyla mine ______10. 22] 51 have the same number. Thus, the gamma lactone D-Ma nnose phenyl hy drazone ______10.22854 of an aldonic acid is represented by .- - - 66 , wh ereas ])-Mannonic pheny Ih y drazide ______10. 2295-1 a gamma lactone present as an auxiliary group is ])-Mannonic 'Y-Iactone ______10. 22966 ind icated by 72 following the location given in 1, 6-Anhydro-/'l-0-altmpyranose ______10. 27268 /'l-])-Mannopyranose 1,2- (meth.vl ortho- parentheses. The first number, 66, shows the acetate) ______10. 22263 presence of the butylene oxide ring in a structure already defined, whereas 72 following the parentheses represents a complete lactone structure. Ordinarily, The numbers selected by the described methods anhydrides involving the glycosidic carbon do not constitute the primary code number and are sufficient require numbers defining the point of substitution; for classifying simple substances. Various schemes thus {3-D-glucopyranose 1,6-anhydride is 10.21268, are used for more complicated substances. in which 68 shows the presence of a hexylene oxido ring involving the main fun c tional group. 3. Representation of Complex Structures D-Fructofuranose-1 ,2-anhydride 10.736(1,2)65, how­ ever, requires the numbers in parentheses, to locate Substitution on the main functional group is shown the oxide ring on the carbon skel eton. In any case directly in the primary code number. Substitution of ambiguity, positions of substitution should be on the carbon chain is indicated by the class number given. and shown more specifically by numbers following Oligosacchal'ides are represented by a series of the primary code number. The class number numbers corresponding to the llllits present. The suffices to show complete substitution by a single glycosidic link.age is shown by an asterisk at the right su bstituent. Thus 2,3 ,4,6-tetra-O-acetyl-a-D-glucose of the code number for each unit. This shows that is ' 12.2110. A partially substituted structure is the structure defined by the preceding number is shown by a group of numbers to the right of the joined in glycosidic linkage to another carbohydrate primary code number. The first number or num­ unit. The parentheses are followed by the code bers, given in parentheses, show the position of number for the next unit. The names for the , III accord with the suggestion of Barton, IIassel, Pitzer, a nd Prelog [21, the used here are obtained by ACS terms axial and equatorial, ahbreviated by a and e respectively, are used to denote positions of groups with respect to the plane of the ring. Bonds connecting ax ial nomenclature rule 35 [1]. For convenience in groups are perpendicular to the mean p lane of the ring; those co nnecting eQ uato· typing, hyphens are used in the code number instead rial groups are directed outward a t a small angle ahove or below the plane of the rin g. of the arrows used in the names. 173 Some examples are depends on the configuration of the highest numbered a-Cellortiose: carbon in the configurational unit. This carbon {3- D-Gl ucopyranosyl-(1---74 )-{3-D-gl ucopyranosyl­ is number 4 in the series and number 5 in (1---74)-a-D-glucopyranose is 30.212*(1-4).212* (1- the hexose series. Basing the alpha and beta names 4).2110. on different reference carbons results in a lack of a-Mal to : correlation between the alpha or beta name and the structure of the anomeric carbon, especially for the a-D-Glucopyranosyl-(1 ---74)-a-D-glucopyranosyl­ pentoses, ketohexoses, and [3 , 4, 5]. A (1---74)-a-D-glucopyranose is 30.211* (1-4).211*(1- change in the names ordinarily used for these sub­ 4).2110. stances is not desirable but for correlation of struc­ : turally related compounds a more fundamental a-D-Galactopyranosyl-(1 ---76)-a-D-glucopyrano­ relationship must be used. The stereomeric prob­ syl- (1---72)-{3-D-fructofuranoside is 30.231*(1-6) lems for furanose and pyranose derivatives are .211 *(1-2).736*. different; hence classification of the two structures will be treated separately . : a-D-Glucopyranosyl- (1 ---72 )-{3-D-fructofurano­ 4 .2. Classifica tion of Furanose Structures side is 20.211*(1-2).736*. The dimensions and normal bond angles of the : atoms comprising the furanose ring are such that a (3-D-Galactopyranosy 1- (1 ---74) - a-D-gi U co pyranose planar ring can be formed with little strain. Al­ is 20.232*(1-4).2110. though very little is known concerning the conforma­ A branched structure is represented by use of tion of furanose rings, intramolecular, and crystal­ braces. For example, a-D-glucopyranosyl-(1 ---74)­ line forces can cause distortion. Thus X-ray studies [a-D-galactopyranosyl-(1---7 6)]-a-D-mannopyranose is have shown that the furanose ring in crystalline sucrose is nonplanar [6). There are few furanose 30.211 *(1-4)} 29 10 structures available for study and no means for pre­ .231 *(1-6 ) . ~ . dicting probable conformation. Hence for the pres­ ent it seems desirable to consider the ring as sub­ composed of one type of struc­ stantially planar, with considerable fl exibility. With tural unit are represented by 4 in the first digit of a planar furanose ring the different configurations for the code number and a sequence of numbers showing carbons 1 to 4 give 16 isomers, 8 in the D series, and the skeleton, configuration, and structure of the their 8 enantiomorphs in the L series . The 8 repre­ monosaccharide unit, followed by numbers showing sentatives of either series consist of two modifica­ the position, or positions of the glycosidic linkages. For example: tions of each of 4 fundamental ring structures, that have, respectively, t he xylo , arabo, lyxo, and ribo is 40.211 *(1-4), configurations. The two modifications of each of is 40.211 *(1 -4)*(1-6), these, differing in t he configuration .of carb~n-1, is 40.211 *(1-6 )*(1-3)*(1-4). can be classified a.s c and t on the basIs of a c~s or The numbers in parentheses for dextran show the trans configuration for the glycosidic group and the presence of glycosidic linkages at carbons 6, 3, and hydroxyl on the adjacent ring carbon. This pro­ 4. The polym eric character of the substance is cedure is applicable to all furanose derivatives and indicated by 4 at the left of the code number. avoids the complications that arise in classification H etero-polysaccharides are classified according to by conventional nomenclature. the various structures present. Thus a polysac­ Table 4 shows that stru cturally related , charide composed of a-D-galactopyranose units, pentoses, hexoses, and higher sugars differ merely {3-D-mannopyranose units, and (3-L-arabinofuranose with respect to R, the substituent group at­ units is 50.231*.222*.136*. The examples cover tached to carbon 4 of the ring. In the hexo­ furanoses which have 5 asymmetric carbons, only 9 few of the many substances that can be classi­ fied; others will be given in future publications. the diffe{'ent configurations of carbon 5 give rise to two isomers for each of the c and t modifica­ tions of the four fundamental ring configurations. 4 . Discussion of Configuration and Con­ To emphasize configurational relatio~ships the h ex?­ formation furanoses in table 4 have been gIven systematlC names based on the configuration of the groups 4.1. Classification of comprising the ring structure, in addition to the conventional names. The systematic names are According to present nomenclature, when an presented to aid in the correlation of related struc­ anomeric pair of sugars or derivatives belongs tures and are not proposed as alternate names for in the D configurational series, the more dextrorota­ the substances. The ketofuranohexoses differ from tory member is called alpha, and the less dextrorota­ the aldofuranopentoses in that the former ha.ve a tory, beta. If the substances belong in the L series, CH20H group in place of the hydrogen of carbon-1 the more levrorotatory member is called alpha. of the latter. Like the aldofuranopentoses, the Assignment of the substance to the D or L series ketofuranohexoses can be classified as c or t accord- 174 TABLE 4. Furanose stntctw'es II

= I cOde------1 .- L6 .-26 .-36 .-46

Aldoses

R = H ______L-'I' h.-eofuranose______L-Erythrofuranose ______(0) (,) R = CH ,on_. ______I)-X ylofuranose ______D-Lyxofuranose______D-Arabin ofuranose______D- Ribofurall ose.

Jl 1 R = C H , OH-C- I D-G lllcofur a n ose ( D-glyeero- D-Mannofuranose ( D-g ly eero- o -A 1 trofurs n ose (D-glveero­ D·A 1I 0furanose (D-glycero-o-rwo­ 6u D-xvlo-aLcLo hexofuraDose) . D-lyxo-a lclo hexofuranose) . D-arabo-a Idohexofu ra nose). aldolJ exofuranose) . on I.-Ielofllranose (L-g/yecro-D-xylo- I T.- G u 10 fll r a n o s e (L-glyeero- L-G alactofura lJose (L-glyecro- D- l/ J'alofuranose (L·ylyeero·D-ribo· a LcI () llexofuranose) . I o-lyxo-aldohexofllranose). I arabo-alcl ohexofu ranose). alclo hexofuranose) . H= C H , OH.6- 1 H

Ketoses (CH ,On on carbon 011 right of form ula)

R= H _ ------I L-X)'llIlofuranose ____ ------1 T.- RibuJOflira nose ______1D-Xylulof uran ose __ ------I D·Ribulofuranose. R= C n ,OH . ___ ._ __ D·Sorbofuranose ___ .______D·Tagatoflifall OSee_. ______. D-l'ructofuranose_. ______. ______D·Psicose.

a All of the co mpounds exist in enaotiomorphic forms, one member of wh ich is re presented here. b ~ rh e product, D~LhreofuraD ose, is classifi ed with T.·threofuranose u nd er code .-16. , Tbe proeluct. o-erythrofllranose, is classified with L-erythrofuranose under code .-26. ing to a cis or a trans rclationship of the glycosidic and Ottar [9], R eeves [10], and others [11] has group with respect to the hydroxyl of the adjacent shown that the pyranose ring invariably assumes ring carbon. There are few furanose derivatives, one of two chair conformations, given in figure 1, and hence for the present separate code numbers unless the ring is altered by bridging to a boat form. are not given to the c and t modifications. Classi­ Reeves [10] has given these two forms the designa­ fication of all furanose derivatives in only four groups tions Cl and Ie respectively. Thus "the Sachse makes comparisons possible with relatively few strainless r ing chair form in which the sixth carbon compounds. atom and the ring project on the same side of the plane formed by carbon atoms 1,2,4, and 5 is 4 .3 . Conformation and Classification of Pyranose Structures

X-ray investigations and other evidence indicate Normal conformations Cl Secondary conformations C2 that the atoms forming the pyranose ring do not lie in a single plane and that the rings can assume + several shapes or conformations [7]. It was fo und in 1937 that if the pyranose sugars are divided into two groups, alpha when carbon 1 and carbon 5 have like configurations and beta when they have unlike + o + configurations, then on bromine oxidation there is 0- hexose Cl 0- hexose C2 marked similarity in the behavior of the alpha sugars on the one hand and of the beta sugars on + the other. This shows that there is an important structural difference in the alpha and beta modifica­ ;1' :-----/-1 tions. The difference was ascribed to the existence + - + a o P of a strainless ring structure in which the alpha and beta positions are not symmetrically located with L - hexose Cl + L-hexQse C2 respect to the carbon-oxygen ring. Several strainless ring forms (or conformations) seemed possible [3]. FIG U R E 1. Conforrnations of the pyranose ring. But at the time this work was done there was no Positions marked + or - show, respectively. the location of tbe reference satisfactory method for deciding which structure group for a 0 or an L confi guration of t he individual carbon. A reference group is defined as an y group otber than h ydrogen. For the historical development of was actually present. Subsequent work by Hassel the designatiou of confi guration, see the excellen t review by C. S. Hudson [8] . 175 designated C1, and its mirror image 1C." This CI or nor mol conformation definition is ambiguous, inasmuch as the mirror o 0 image of a whole molecule in the C1 conformation likewise meets Reeves' criterion for a C1 conforma­ tion. Unfortunately, "mirror image" was used in the definition in the sense of the ring skeleton only, 7 ~----r' 7 HO# 7 HOr but was then applied to the whole molecule. This ° 6 e led to a different classification for the D and L forms o-gluco- 0- manno- of derivatives of galactose and of arabinose. To avoid the term "mirror image" in its special sense,

C1 is used in the present classification to represent O}-H the conformation of the pyranose ring in which --t -::," t carbon 6 is in an equatorial position, and C2 is l used to represent the conformation in which carbon "Ok' ~p : 6 is in an axial position. With this classification, o-galacto- o-talo- the mirror image of D-galactopyranose C1 is L-galac­ topyranose C1 and the "inverted" conformation of the ring for either enantiomorph is designated by C2. ir------r-'" The two conformations differ in that the groups t )" :7 in axial positions of one are in equatorial positions r ~ of the other, and the reverse. OH POH : o- Ido- 0- gulo- Figure 2 shows the C1 structures for the aldo­ o o hexopyranoses of the D-configurational series. 4 Table 5 lists the reference groups attached to the ring ac­ cording to whether they are in axial or equatorial positions. On the left side of the table, the C1 ° ~- ----{'I7 conformations are listed with their code numbers. 7 a Opposite each of the C1 conformations is a C2 con­ OH OH formation with the same arrangement of reference o-oltro- 0- 0110- groups, except for the one attached to carbon 5. The arrangement of the reference groups common to FIG URE 2. F1tndamental pyranose types. both substances is given in the center of the table. For example, either a-D-glucopyranose C1 or a-L­ glucopyranose C1 has the a e e e e conformation which is like the a e e e a conformation of either {3-L­ idopyranose C2 or {3-D-idopyranose C2 except for TABLE 5. Axial and equatorial positions of Teference grmtps the arrangement of the groups at carbon 5. In the in aldohexopyranose stntct1treS classification system code numbers .--1 and .--2 are given to substances with the C1 conformation having 01, or normal conforma- Character or reror· C2, or secondary con ~ tion (reference group ence group formation (rererence axial and equatorial glycosidic groups, respectively. group at carbon 5 axial) Code numbers .--3 and .--4 are given to substances at carbon 5 equatorial) with the C2 conformation having axial and equa­ Carbon· torial glycosidic groups, respectively. Pyranose de­ Code Configura tion Configura tion Code rivatives having a conformation other than the C1 or 1 2 3 4 C2 are given the code number .--5, regardless of ------configuration at the anomeric carbon. • ·11 a·glueo· a e e e {J· ido· · ·53 Undoubtedly the conformation of the ring is not • ·12 {J·glueo· 0 e e e a-ido- · ·54 • ·21 a-manno- a a e e {J·galo· . ·63 the same for all pyranose derivatives and in some · -22 {3-manno - e a c e a-gulo· · -64 cases several conformations may exist. This may · -31 a-galaet o- a e c a {J·altro· · -73 account, as previously pointed out [3], for anomalous · -32 {J·gala.cta· e e e a a·allro· · -74 values for the differences in molecular rotations ob­ • -41 a-tala· a a e a {J·allo- · -83 tained by application of Hudson's rules of isorotation • -42 {J·tala· e a e a a·allo- · -84 [12]. Some sugar derivatives exist that for stereo­ · -51 a-ido- a a a a {J-gluco· · -13 meric reasons are limited to certain conformations. · ·52 {J-ido- e a a a a-glueo- · ·14 For example, 1,4-anhydroglucopyranose requires a · -61 a-gulo- a e a a fJ-man no- · -23 {J-galo· 0 e a a a-manna- boat-shaped ring in which carbons 1 and 4 are · -62 · -24 · -71 a-aUTO- a a a e {J-galacto· · -33 directed toward each other. However, the con­ · -72 {J·altro· e a a e a·galacto· · -34 sistent relationship found between the rates of oxi- · -81 a·allo· a e a e {J·tala- · -43 · -82 {J-allo· e 0 a e a-tala · · -44 4. 'l'hc L (or ms are not given because they are lnirmf images and can be con- structed from the diagrams of fi ~ ure 1. .

176 dation with bromine and the ·c onfiguration of the att ached groups appear to be in a particularly anomeric carbon in the aldohexopyranose series is favorable position to influence the conformation of evidence of the prevalence of a common ring con­ the ring. P erhaps this accounts for t he unexp ectedly formation in at least 10 (out of a possible 16) aldo­ large influence of the configuration of carbon 3 on hexopyranoses studied by bromine oxidation [3, 4]. the relative reactivities of the alpha and beta modi­ The relative stability of the two conformations de­ fications. Another observation which may depend pends on a number of factors, particularly the tend­ on the effect of the configuration of carbon 3, is that ency of large groups to take an equatorial rather in the pentose series where the ring forming carbon than an axial position [9, 10] . The CH20H group is not asymmetric, each pentose resembles t he h exose of the aldohexopyranoses has a strong tendency to in which carbons 3 and 5 have opposite configura­ assume the equatorial position, and this accounts tions." Thus xylose, lyxose, arabinose, and ribose for the fact that most aldohexopyranoses have the derivatives resemble the corresponding derivatives C1 conformation. of glucose, mannose, galactose, and talose, respec­ The pyranose forms of the pentoses and keto­ tively, more closely than they resemble the deI·iva­ hexoses differ from those of the aldohexoses in that tives of idose, gulose, alt rose, and allose [3 , 4, 5]. at carbon 5 they do not have a CH20H group and H ence for classification purposes the aldopentoses hence the ring-forming carbon is nonasymmetric. are given code numbers corresponding to those of Thus each pentose or ketohexose is structurally the fu'st-named group of substances. For example, related to two aldohexoses. The relationship for the code number of a-D-xylopYTanose (a e e e) is a-D-xylose, a typical pen tose, is shown in figure 3. .1110, whereas, the code number for the hypothetical The structure for a-D-xylopyranose could be derived "inverted" or C2 conformation (e a a a) is .11 40. by replacing the CH 20H group of either a-D-gluco­ The pyranose derivatives of the relat ed ketohexoses, pyranose or ,B-L-idopyranose by hydrogen . The sorbose, tagat ose, fructose, and psicose are likewise conformation of a-D- xylopyranose produced by this given code numbers corresponding t o the glucose, hypothetical procedure would depend on the con­ mannose, galactose, and talose configm'ations, re­ formation of the parent hexose. a-D-Glucopyranose spectively. C 1 and ,B-L-idopyranose C2 would yield a form of The ketoses differ from the aldoses in that t he a-D-xylopyranose having equatorial hydroxyls at glycosidic carbon has a OH 20H group in place of carbons 2, 3, and 4, and an axial hydroxyl at carbon the aldehydic hydrogen . The presence of this group 1. But a-D-glucopyranose C2 and ,B-L-idopyranose greatly alters the equilibrium for the anomeric C1 would yield a form of a-D-xylopyranose having modifications in solution. Apparently the CH 20H axial hydroxyls at carbons 2, 3, and 4, and an group tends to assume an equatori al position anal­ equatorial hydroxyl at carbon 1. ogous to that taken by th e CH 20H group in the C1 Apparently the pentoses tend t o assume the con­ aldohexopyranoses. This accounts for the fact that formation with the hydroxyl of carbon 3 in an equilibrium solutions of fructose, sorbose, tagatose, equat orial rather than an axial position. In this mannohept uJose, glucohep tulose, and other ketoses connection Isbell aDd Frush wrote as follows in contain almost exclusively the pyranose modification 1940 [5]: "As may be not ed from a space model, having an equatorial CH 20H group at carbon 2. carbon 3 lies opposite the oxygen of the ring and its At present any attempt to assign definite con­ formations to all pyranose derivatives is prematm e.

OH There is need, however , for consideration of t he o special stereomeric factors associated with the ring \ conformation most likely t o be present in any sub­ l------'..-_ R st ance. This is particularly true for the evaluation of infrared absorption, b ecause this property is extremely sensitive to the molecular structure. HO OH OH OH HO H ence some method of classification is desirable. a-D-glucopyranose Cl /3- L- ldopyr anose CI a OH A definitive classification requires that the structures o of the compounds shall have been established un­ equivocally. As this is not true with pyranose de­ rivatives in general, it is necessary to make an arbitrary classification. By comparison of the in­

HO frared spectra of substances classified in the arbit rary manner, exceptional properties may be discovered o OH and ultimately explained in terms of conformation, or of molecular structm es at present unknown. As a working hypothesis, in the absence of unequiv­ ocal evidence to the contrary, the C1 conformation is assumed as a fu'st choice and the C2 only as a HO OH OH second choice. With provisional assignments, in­ a-D- xylopyronose C1 frared absorption and other data can be examined for correlations based on either the C1 or t he 02 F IGUR E 3. Structurally related hexoses and pentoses. conformation.

177 References [8] C. . Hudson, Advances in Carbohydrate Chem. 3, 1 5. (1948). [9] O. Hassel and B. Ottar, Acta Chem. Scand. 1, 929 (1947). [1] ACS Rules on Carbohydrate Nomenclature, Chem. Eng. [10] R. E. Reeves, Advances in Carbohydrate Chem. 6, 107 News 31, 1776 (1953). (1951). [2] D. H. R. Barton, O. Hassel, K. S. Pitzer, and V. Prelog, [11] J. A. Mills, Advances in Carbohydrate Chern. 10, 1 Nature 172,1096 (1953). (1955) . [3] H. S. Isbell, J. Research NBS 18, 505 (1937) RP990. [12] C. S. Hudson, J. Am. Chern. Soc. 52, 1680 (1930). [4] H. S. Isbell and W. W. Pigman, J. Research NBS 18, 141 (1937) RP969. [5] H. S. Isbell a nd H . L. Frush, J. Research NBS 2<1, 125 (1940) RP1274. [6] C. A. Beevers and W. Cochran, Nature 157, 872 (1946). [7] O. L. Sponsler and W. H . Dore, Ann. Rev. Biochem. 5, 63 (1936). WA SHING'l'ON, May 29, 1956.

178 U, S. GO VERNMEN T PR IN TI NG OFFICE: 1956

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