INTERNATIONAL UNION OF PURE AND APPLIED CHEMISTRY and INTERNATIONAL UNION OF BIOCHEMISTRY AND MOLECULAR BIOLOGY JOINT COMMISSION ON BIOCHEMICAL NOMENCLATURE ~ NOMENCLATURE OF CARBOHYDRATES (Recommendations 1996) Prepared Jot publication by ALAN D. McNAUGHT The Royal Society of Chemistry, Thomas Graham House, Science Park, Milton Road, Cambridge CB4 4WF, UK *Members of the Commission (JCBN) at various times during the work on this document (1983-1996) were as follows: Chairmen: H.B.F. Dixon (UK), J.F.G. Vliegenthart (Netherlands), A. Cornish-Bowden (France); Secre- taries: A. Comish-Bowden (France), M.A. Chester (Sweden), A.J. Barrett (UK), J.C. Rigg (Netherlands); Members: J.R. Bull (RSA), R. Cammack (UK), D. Coucouvanis (USA), D. Horton (USA), M.A.C. Kaplan (Brazil), P. Karlson (Germany), C. Li6becq (Belgium), K.L. Loening (USA), G.P. Moss (UK), J. Reedijk (Netherlands), K.F. Tipton (Ireland), S. Velick (USA), P. Venetianer (Hungary). Additional contributors to the formulation of these recommendations: Expert Panel: D. Horton (USA) (Convener), O. Achmatowicz (Poland), L. Anderson (USA), S.J. Angyal (Australia), R. Gigg (UK), B. Lindberg (Sweden), D.J. Manners (UK), H. Paulsen (Germany), R. Schauer (Germany). Nomenclature Committee oflUBMB (NC-IUBMB) (those additional to JCBN): A. Bairoch (Switzerland), H. Berman (USA), H. Bielka (Germany), C.R Cantor (USA), W. Saenger (Germany), N. Sharon (israel), E. van Lenten (USA), E.C. Webb (Australia). American Chemical Society Committee jor Carbohydrate Nomenclature: D. Horton (Chairman), L. Anderson, D.C. Baker, H.H. Baer, J.N. BeMiller, B. Bossenbroek, R. W. Jeanloz, K.L. Loening, W. A. Szarek, R.S. Tipson, W.J. Whelan, R.L. Whistler. Corresponding Members of the ACS Committee,lbr Carbohydrate Nomenclature (other than JCBN and the expert panel): R.F. Brady (USA), J.S. Brimacombe (UK), J.G. Buchanan (UK), B. Coxon (USA), J. Defaye (France), N.K. Kochetkov (Russia), R.U. Lemieux (Canada), R.H. Marchessault (Canada), J.M. Webber (UK). Correspondence oil these recommendations should be addressed to Dr. Alan D. McNaught at the above address or to any member of the Commission. Reproduced from Pure AMd. Chem.. 1996.68, 1919. Copyright © 1996 International Union of Pure and Applied Chemistry {IUPAC). Published by Elsevier Science Ltd.
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`NOMENCLATURE OF CARBOHYDRATES (Recommendations 1996) Contents Preamble 2-Carb-O. Historical development of carbohydrate nomenclature 0. l. Early approaches 0.2. The contribution of Emil Fischer 0.3. Cyclic forms 0.4. Nomenclature commissions 2-Carb-1. Definitions and conventions 1,1. Carbohydrates 1.2. Monosaccharides (aldoses and ketoses) 1.3. Dialdoses 1.4. Diketoses 1.5. Ketoaldoses (aldoketoses) 1.6. Deoxy sugars 1.7. Amino sugars 1.8. Alditols 1.9. Aldonic acids 1.10. Ketoaldonic acids 1.11. Uronic acids 1.12. Aldaric acids 1.13. Glycosides 1.14. Oligosaccharides 1.15. Polysaccharides 1.16. Conventions for examples 2-Carb-2, Parent monosaccharides 2.1. Choice of parent structure 2.2. Numbering and naming of the parent structure 2-Carb-3. The Fischer projection of the acyclic form 2-Carb-4. Configurational symbols and prefixes 4.1. Use of D and L 4,2. The configurational atom 4.3. Configurational prefixes in systematic names 4.4. Racemates and meso forms 4.5. Optical rotation 2-Carb-5. Cyclic forms and their representation 5.1. Ring size 5.2. The Fischer projection 5.3. Modified Fischer projection 5.4. The Haworth representation 5.5. Unconventional Haworth representations 5.6. The Mills depiction 5.7. Depiction of conformation 5.8. Conformations of acyclic chains 2-Carb-6. Anomeric forms; use of o~ and 6.1. The anomeric centre 6.2. The anomeric reference atom and the anomeric configurational symbol 6.3. Mixtures of anomers 6.4. Use of o~ and 13 2-Carb-7. Conformation of cyclic forms 7.1. The conformational descriptor 7.2. Notation of ring shape 7,3. Notation of variants 7.4. Enantiomers 2-Carb-8. Aldoses 8.1. Trivial names 8.2. Systematic names 8.3. Multiple configurational prefixes
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`8.4. Multiple sets of chiral centres 8.5. Anomeric configuration in cyclic forms of higher aldoses 2-Carb-9. Dialdoses 2-Carb- l O. Ketoses 10.1. Classification 10.2. Trivial names 10.3. Systematic names 10.4. Configurational prefixes 2-Carb-11. Diketoses 11.1. Systematic names 11.2. Multiple sets of chiral centres 2-Carb-12. Ketoaldoses (aldoketoses, aldosuloses) 12.1. Systematic names 12.2. Dehydro names 2-Carb-13. Deoxy sugars 13.1. Trivial names 13.2. Names derived from trivial names of sugars 13.3. Systematic names 13.4. Deoxy alditols 2-Carb-14. Amino sugars 14. I. General principles 14.2. Trivial names 14.3. Systematic names 2-Carb-15. Thio sugars and other chalcogen analogues 2-Carb-16. Other substituted monosaccharides 16.1. Replacement of hydrogen at a non-terminal carbon atom 16.2. Replacement of OH at a non-terminal carbon atom 16.3. Unequal substitution at a non-terminal carbon atom 16.4. Terminal substitution 16.5. Replacement of carbonyl oxygen by nitrogen (imines, hydrazones, osazones etc.) 16.6. Isotopic substitution and isotopic labelling 2-Carb-17. Unsaturated monosaccharides 17.1. General principles 17.2. Double bonds 17.3. Triple bonds and cumulative double bonds 2-Carb-18. Branched-chain sugars 18.1. Trivial names 18.2. Systematic names 18.3. Choice of parent 18.4. Naming the branches 18.5. Numbering 18.6. Terminal substitution 2-Carb-19. Alditols 19.1. Naming 19.2. meso Forms 2-Carb-20. Aldonic acids 20.1. Naming 20.2. Derivatives 2-Carb-21. Ketoaldonic acids 21.1. Naming 21.3. Derivatives 2-Carb-22. Uronic acids 22.1. Naming and numbering 22.2. Derivatives 2-Carb-23. Aldaric acids 23.1. Naming 23.2. meso Forms 23.3. Trivial names 23.4. Derivatives 2-Carb-24. O-Substitution 24. I. Acyl (alkyl) names
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`24.2. Phosphorus esters 24.3. Sulfates 2-Carb-25. N-Substitution 2-Carb-26. Intramolecular anhydrides 2-Carb-27. Intermolecular anhydrides 2-Carb-28. Cyclic acetals 2-Carb-29. Hemiacetals and hemithioacetals 2-Carb-30. Acetals, ketals and their thio analogues 2-Carb-3 I. Names for monosaccharide residues 31.1. Glycosyi residues 31.2. Monosaccharides as substituent groups 31.3. Bivalent and tervalent residues 2-Carb-32. Radicals, cations and anions 2-Carb-33. Glycosides and glycosyl compounds 33.1. Definitions 33.2. Glycosides 33.3. Thioglycosides. 33.4. Selenoglycosides 33.5. Glycosyl halides 33.6. N-Glycosyl compounds (glycosylamines) 33.7. C-Glycosyl compounds 2-Carb-34. Replacement of ring oxygen by other elements 34.1. Replacement by nitrogen or phosphorus 34.2. Replacement by carbon 2-Carb-35. Carbohydrates containing additional rings 35.1. Use of bivalent substituent prefixes 35.2. Ring fusion methods 35.3. Spiro systems 2-Carb-36. Disaccharides 36.1. Definition 36.2. Disaccharides without a free hemiacetal group 36.3. Disaccharides with a free hemiacetal group 36.4. Trivial names 2-Carb-37. Oligosaccharides 37.1. Oligosaccharides without a free hemiacetal group 37.2. Oligosaccharides with a free hemiacetal group 37.3. Branched oligosaccharides 37.4. Cyclic oligosaccharides 37.5. Oligosaccharide analogues 2-Carb-38. Use of symbols for defining oligosaccharide structures 38.1. General considerations 38.2. Representations of sugar chains 38.3. The extended form 38.4. The condensed form 38.5. The short form 2-Carb-39. Polysaccharides 39.1. Names for homopolysaccharides 39.2. Designation of configuration of residues 39.3. Designation of linkage 39.4. Naming of newly discovered polysaccharides 39.5. Uronic acid derivatives. 39.6. Amino sugar derivatives 39.7. Polysaccharides composed of more than one kind of residue 39.8. Substituted residues 39.9. Glycoproteins, proteoglycans and peptidoglycans References Appendix Trivial Names for Carbohydrates, with their Systematic Equivalents Glossary of Glycose-based Terms
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`Preamble These Recommendations expand and replace the Tentative Rules for Carbohydrate Nomenclature [ 1 ] issued in 1969 jointly by the IUPAC Commission on the Nomenclature of Organic Chemistry and the IUB-IUPAC Commission on Biochemical Nomenclature (CBN) and reprinted in [2]. They also replace other published JCBN Recommendations [3-7] that deal with specialized areas of carbohydrate terminology; however, these documents can be consulted for further examples. Of relevance to the field, though not incorporated into the present document, are the following recommendations: Nomenclature of cyclitols, 1973 [8] Numbering of atoms in myo-inositol, 1988 [9] Symbols for specifying the conformation of polysaccharide chains, 1981 [10] Nomenclature of glycoproteins, glycopeptides and peptidoglycans, 1985 [ 11 [ Nomenclature of glycolipids, in preparation [ 12] The present Recommendations deal with the acyclic and cyclic forms of monosaccharides and their simple derivatives, as well as with the nomenclature of oligosaccharides and polysaccharides. They are additional to the Definitive Rules for the Nomenclature of Organic Chemistry [13,14] and are intended to govern those aspects of the nomenclature of carbohydrates not covered by those rules. 2-Carb-O. Historical development of carbohydrate nomenclature [15] 2-Carb-0.1. Early approaches In the early nineteenth century, individual sugars were often named after their source, e.g. grape sugar (Traubenzucker) for glucose, cane sugar (Rohrzucker) for saccharose (the name sucrose was coined much later). The name glucose was coined in 1838; Kekul6 in 1866 proposed the name 'dextrose' because glucose is dextrorotatory, and the laevorotatory 'fruit sugar' (Fruchtzucker, fructose) was for some time named 'laevulose' (American spelling 'levulose'). Very early, consensus was reached that sugars should be named with the ending '-ose', and by combination with the French word 'cellule' for cell the term cellulose was coined, long before the structure was known. The term 'carbohydrate' (French 'hydrate de carbone') was applied originally to monosaccharides, in recognition of the fact that their empirical composition can be expressed as Cn(H20)n. However the term is now used generically in a wider sense (see 2-Carb-1.1). 2-Carb-0.2. The contribution of Emil Fischer Emil Fischer [ 16] began his fundamental studies on carbohydrates in 1880. Within ten years, he could assign the relative configurations of most known sugars and had also synthesized many sugars. This led to the necessity to name the various compounds. Fischer and others laid the foundations of a terminology still in use, based on the terms triose, tetrose, pentose, and hexose. He endorsed Armstrong's proposal to classify sugars into aldoses and ketoses, and proposed the name fructose for laevulose, because he found that the sign of optical rotation was not a suitable criterion for grouping sugars into families. The concept of stereochemistry, developed since 1874 by van't Hoff and Le Bel, had a great impact on carbohydrate chemistry because it could easily explain isomerism. Emil Fischer introduced the classical projection formulae for sugars, with a standard orientation (carbon chain vertical, carbonyl group at the top); since he used models with flexible bonds between the atom s , he could easily 'stretch' his sugar models into a position suitable for projection. He assigned to the dextrorotatory glucose (via the derived glucaric acid) the projection with the OH group at C-5 pointing to the right, well knowing that there was a 50% chance that this was wrong. Much later (Bijvoet, 1951), it was proved correct in the absolute sense. Rosanoff in 1906 selected the enantiomeric glyceraldehydes as the point of reference; any sugar derivable by chain lengthening from what is now known as D-glyceraldehyde belongs to the D series, a convention still in use. 2-Carb-0.3. Cyclic forms Towards the end of the nineteenth century it was realized that the free sugars (not only the glycosides) existed as cyclic hemiacetals or hemiketals. Mutarotation, discovered in 1846 by Dubrunfaut, was now interpreted as being due to a change in the configuration of the glycosidic (anomeric) carbon atom. Emil Fischer assumed
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`the cyclic form to be a five-membered ring, which Tollens designated by the symbol <1,4>, while the six-membered ring received the symbol < 1,5>. In the 1920s, Haworth and his school proposed the terms 'furanose' and 'pyranose' for the two forms. Haworth also introduced the 'Haworth depiction' for writing structural formulae, a convention that was soon widely followed. 2-Carb-0.4. Nomenclature commissions Up to the 1940s, nomenclature proposals were made by individuals; in some cases they were followed by the scientific community and in some cases not. Official bodies like the International Union of Chemistry, though developing and expanding the Geneva nomenclature for organic compounds, made little progress with carbohydrate nomenclature. The IUPAC Commission on Nomenclature of Biological Chemistry put forward a classification scheme for carbohydrates, but the new terms proposed have not survived. However in 1939 the American Chemical Society (ACS) formed a committee to look into this matter, since rapid progress in the field had led to various misnomers arising from the lack of guidelines. Within this committee, the foundations of modem systematic nomenclature for carbohydrates and derivatives were laid: numbering of the sugar chain, the use of D and L and o~ and 13, and the designation of stereochemistry by italicized prefixes (multiple prefixes for longer chains). Some preliminary communications appeared, and the final report, prepared by M.L. Wolfrom, was approved by the ACS Council and published in 1948 [17]. Not all problems were solved, however, and different usages were encountered on the two sides of the Atlantic. A joint British-American committee was therefore set up, and in 1952 it published 'Rules for Carbohydrate Nomenclature' [18]. This work was continued, and a revised version was endorsed in 1963 by the American Chemical Society and by the Chemical Society in Britain and published [19]. The publication of this report led the IUPAC Commission on Nomenclature of Organic Chemistry to consider the preparation of a set of IUPAC Rules for Carbohydrate Nomenclature. This was done jointly with the IUPAC-IUB Commission on Biochemical Nomenclature, and resulted in the 'Tentative Rules for Carbohydrate Nomenclature, Part I, 1969', published in 1971/72 in several joumals [1]. It is a revision of this 1971 document that is presented here. In the present document, recommendations are designated 2-Carb-n, to distinguish them from the Carb-n recommendations in the previous publication. 2-Carb-1. Definitions and conventions 2-Carb-l.1. Carbohydrates The generic term 'carbohydrate' includes monosaccharides, oligosaccharides and polysaccharides as well as substances derived from monosaccharides by reduction of the carbonyl group (alditols), by oxidation of one or more terminal groups to carboxylic acids, or by replacement of one or more hydroxy group(s) by a hydrogen atom, an amino group, a thiol group or similar heteroatomic groups. It also includes derivatives of these compounds. The term 'sugar' is frequently applied to monosaccharides and lower oligosaccharides. It is noteworthy that about 3% of the compounds listed by Chemical Abstracts Service (i.e. more than 360 000) are named by the methods of carbohydrate nomenclature. Note. Cyclitols are generally not regarded as carbohydrates. Their nomenclature is dealt with in other recommendations [8,9]. 2-Carb-l.2. Monosaceharides Parent monosaccharides are polyhydroxy aldehydes H-[CHOH]n-CHO or polyhydroxy ketones H-[CHOH]n- CO-[CHOH]m-H with three or more carbon atoms. The generic term 'monosaccharide' (as opposed to oligosaccharide or polysaccharide) denotes a single unit, without glycosidic connection to other such units. It includes aldoses, dialdoses, aldoketoses, ketoses and diketoses, as well as deoxy sugars and amino sugars, and their derivatives, provided that the parent compound has a (potential) carbonyl group. 1.2.1. Aldoses and ketoses Monosaccharides with an aldehydic carbonyl or potential aldehydic carbonyl group are called aldoses; those with a ketonic carbonyl or potential ketonic carbonyl group, ketoses. Note. The term 'potential aldehydic carbonyl group' refers to the hemiacetal group arising from ring closure. Likewise, the term 'potential ketonic carbonyl group' refers to the hemiketat structure (see 2-Carb-5).
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`1.2.2. Cyclic forms Cyclic hemiacetals or hemiketals of sugars with a five-membered (tetrahydrofuran) ring are called furanoses, those with a six-membered (tetrahydropyran) ring pyranoses. For sugars with other ring sizes see 2-Carb-5. 2-Carb-l.3. Diaidoses Monosaccharides containing two (potential) aldehydic carbonyl groups are called dialdoses (see 2-Carb-9). 2-Carb-l.4. Diketoses Monosaccharides containing two (potential) ketonic carbonyl groups are termed diketoses (see 2-Carb-1 I). 2-Carb-l.5. Ketoaldoses (aldoketoses, aldosuloses) Monosaccharides containing a (potential) aldehydic group and a (potential) ketonic group are called ketoald- oses (see 2-Carb-12); this term is preferred to the alternatives on the basis of 2-Carb-2.1.1 (aldose preferred to ketose). 2-Carb-l.6. Deoxy sugars Monosaccharides in which an alcoholic hydroxy group has been replaced by a hydrogen atom are called deoxy sugars (see 2-Carb- 13). 2-Carb-l.7 Amino sugars Monosaccharides in which an alcoholic hydroxy group has been replaced by an amino group are called amino sugars (see 2-Carb-14). When the hemiacetal hydroxy group is replaced, the compounds are called glycosyl- amines. 2-Carb-l.8. Alditols The polyhydric alcohols arising formally from the replacement of a carbonyl group in a monosaccharide with a CHOH group are termed alditols (see 2-Carb-19). 2-Carb-l.9. Aldonic acids Monocarboxylic acids formally derived from aldoses by replacement of the aldehydic group by a carboxy group are termed aldonic acids (see 2-Carb-20). 2-Carb-l.10. Ketoaldonic acids Oxo carboxylic acids formally derived from aldonic acids by replacement of a secondary CHOH group by a carbonyl group are called ketoaldonic acids (see 2-Carb-21). 2-Carb-l.ll. Uronic acids Monocarboxylic acids formally derived from aldoses by replacement of the CH2OH group with a carboxy group are termed uronic acids (see 2-Carb-22). 2-Carb-l.12. Aldaric acids The dicarboxylic acids formed from aldoses by replacement of both terminal groups (CHO and CH2OH) by carboxy groups are called aldaric acids (see 2-Carb-23). 2-Carb-l.13. Glycosides Glycosides are mixed acetals formally arising by elimination of water between the hemiacetal or hemiketal hydroxy group of a sugar and a hydroxy group of a second compound. The bond between the two components is called a glycosidic bond. For an extension of this definition, see 2-Carb-33. 2-Carb-l.14. Oligosaeeharides Oligosaccharides are compounds in which monosaccharide units are joined by glycosidic linkages. According to the number of units, they are called disaccharides, trisaccharides, tetrasaccharides, pentasaccharides etc. The borderline with polysaccharides cannot be drawn strictly; however the term 'oligosaccharide' is commonly used to refer to a defined structure as opposed to a polymer of unspecified length or a homologous mixture. When the linkages are of other types, the compounds are regarded as oligosaccharide analogues. (See 2-Carb-37.)
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`10 Note. This definition is broader than that given in [6], to reflect current usage. 2-Carb-l.15. Polysaccharides 'Polysaccharide' (glycan) is the name given to a macromolecule consisting of a large number of monosac- charide (glycose) residues joined to each other by glycosidic linkages. The term poly(glycose) is not a full synonym for polysaccharide (glycan) (cf. [20]), because it includes macromolecules composed of glycose residues joined to each other by non-glycosidic linkages. For polysaccharides containing a substantial proportion of amino sugar residues, the term polysaccharide is adequate, although the term glycosaminoglycan may be used where particular emphasis is desired. Polysaccharides composed of only one kind of monosaccharide are described as homopolysaccharides (homoglycans). Similarly, if two or more different kinds of monomeric unit are present, the class name heteropolysaccharide (heteroglycan) may be used. (See 2-Carb-39.) The term 'glycan' has also been used for the saccharide component of a glycoprotein, even though the chain length may not be large. The term polysaccharide has also been widely used for macromolecules containing glycose or alditol residues in which both glycosidic and phosphate diester linkages are present. 2-Carb-l.16. Conventions for examples 1.16.1. Names of examples are given with an initial capital letter (e.g. 'L-glycero-~-D-gluco-Heptopyranose') to clarify the usage in headings and to show which letter controls the ordering in an alphabetical index. 1.16.2. The following abbreviations are commonly used for substituent groups in structural formulae: Ac (acetyl), Bn or PhCH2 (benzyl), Bz or PhCO (benzoyl), Et (ethyl), Me (methyl), Me3Si (not TMS) (trimethylsilyl), ButMe2Si (not TBDMS) (tert-butyldimethylsilyl), Ph (phenyl), Tf (triflyl = trifluoromethane- sulfonyl), Ts (tosyl = toluene-p-sulfonyl), Tr (trityl). 2-Carb-2. Parent monosaccharides 2-Carb-2.1. Choice of parent structure In cases where more than one monosaccharide structure is embedded in a larger molecule, a parent structure is chosen on the basis of the following criteria, applied in the order given until a decision is reached: 2.1.1. The parent that includes the functional group most preferred by general principles of organic nomenclature [ 13,14]. If there is a choice, it is made on the basis of the greatest number of occurrences of the most preferred functional group. Thus aldaric acid > uronic acid/ketoaldonic acid/aldonic acid > dialdose > ketoaldose/aldose > diketose > ketose. 2.1.2. The parent with the greatest number of carbon atoms in the chain, e.g. a heptose rather than a hexose. 2.1.3. The parent with the name that comes first in an alphabetical listing based on: 2.1.3.1. the trivial name or the configurational prefix(es) of the systematic name, e.g. allose rather than glucose, a gluco rather than a gulo derivative; 2.1.3.2. the configurational symbol D rather than L ; 2.1.3.3. the anomeric symbol cc rather than 13. 2.1.4. The parent with the most substituents cited as prefixes (bridging substitution, e.g. 2,3-O-methylene, is regarded as multiple substitution for this purpose). 2.1.5. The parent with the lowest locants (see [ 14], p. 17) for substituent prefixes. 2.1.6. The parent with the lowest locant for the first-cited substituent. The implications of these recommendations for branched-chain structures are exemplified in 2-Carb-18. Note 1. To maintain homomorphic relationships between classes of sugars, the (potential) aldehyde group of a uronic acid is regarded as the principal function for numbering and naming (see 2-Carb-2.2.1 and 2-Carb-22). Note 2. To maintain integrity of carbohydrate names, it is sometimes helpful to overstep the strict order of principal group preference specified in general organic nomenclature [ 13,14]. For example, a carboxymethyl-substituted sugar can be named as such, rather than as an acetic acid derivative (see 2-Carb-31.2).
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`2-Carb-2.2. Numbering and naming the parent structure The basis for the name is the structure of the parent monosaccharide in the acyclic form. Charts I and IV (2-Carb-10) give trivial names for parent aldoses and ketoses with up to six carbon atoms. 2-Carb-8.2 and 2-Carb-10.3 describe systematic naming procedures. II CHO H--(~--OH CH2OH D-Glyceraldehyde D-glycero CHO CHO H--C--OH HO--C--H H--C--OH H--C--OH (~H2OH CH2OH D-Erythrose O-Threose D-erythro D.threo CHO CHO CHO CHO H--C--OH HO--C--H H--C--OH HO--C--H i H--C--OH H--C--OH HO-C--H HO-C--H H--C--OH H--C--OH H--C--OH H--C--OH CH2OH (~H2OH (~H2OH (~H2OH D-Ribose D-Arabinose D-Xylose D-Lyxose D-ribo D-arabino D-xylo D-lyxo (D-Rib) (D-Ara) (O-Xyl) (D-Lyx) CHO CHO CHO CHO CHO CHO CHO CHO ' 6 (5 ..... H--C~OH HO-- --H H-- --OH Ho--C--H H--C~OH HO-C--H H--C--OH HO-C--H H--I~OH H--(~--OH HO--C--H HO--(~--H H--C--OH H--C--OR HO--C--H HO-C--H i i H--C--OH H--C--OH H--C--OH H--C--OH HO--C, ~H HO--C, --H HO--C--H HO-C--H H--(~--OH H--C--OH H--C--OH H-- ,C--OH H--C--OH H--C--OH H--C--OH H-C--OH (~H2OH (~H2OH (~H2OH CH2OH (~H2OH (~H2OH (~HzOH (~H2OH D-Allose D-Altrose D-Glucose o-Mannose D-Gulose D-Idose D-Galactose D-Talose D-a#o D-altro D-gluco D-manno D-gulo D-ido D-galacto D-talo (D-All) (D-AIt) (D-GIc) (D-Man) (D-Gul) (D-Ido) (D-Gal) (D-Tal) Chart I. Trivial names (with recommended three-letter abbreviations in parentheses) and structures (in the aldehydic, acyclic form) of the aldoses with three to six carbon atoms. Only the D-forms are shown; the L-forms are the mirror images. The chains of chiral atoms delineated in bold face correspond to the configurational prefixes given in italics below the names 2.2.1. Numbering The carbon atoms of a monosaccharide are numbered consecutively in such a way that: 2.2.1.1. A (potential) aldehyde group receives the locant 1 (even if a senior function is present, as in uronic acids; see 2-Carb-2.1, note 1); 2.2.1.2. The most senior of other functional groups expressed in the suffix receives the lowest possible locant, i.e. carboxylic acid (derivatives) > (potential) ketonic carbonyl groups. 2.2.2. Choice of parent name The name selected is that which comes first in the alphabet (configurational prefixes included). Trivial names are preferred for parent monosaccharides and for those derivatives where all stereocentres are stereochemically unmodified.
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`12 Examples: CH2OH I HOCH I HCOH I HOCH I HOCH I CH2OH L-Glucitol not D-gulitoI CH2OH HOCH HCOH HOCH L-gluco - C----O HOCH HOCH L-erythro - HOCH I CH2OH L-erythro-L-gluco-Non-5-ulose not D-threo-D-allo-non-5-ulose 2.2.3. Choice between alternative names for substituted derivatives When the parent structure is symmetrical, preference between alternative names for derivatives should be given according to the following criteria, taken in order: 2.2.3.1. The name including the configurational symbol D rather than L. Example: CH2OH I HCOH I HOCH I HCOMe I CH2OH 4-O-MethyI-D-xylitol not 2- O-methyl-L-xylitol 2.2.3.2. The name that gives the lowest set of ]ocants (see [14], p. 17) to the substituents present. Example: ICH2OH MeOCH I MeOCH 1 HCOH I HCOMe t CH2OH 2,3,5-Tri- O-methyI-D-mannitol not 2,4,5-tri-O-methyI-D-mannitol 2.2.3.3. The name that, when the substituents have been placed in alphabetical order, possesses the lowest locant for the first-cited substituent. Example: CIH2 OH AcOCH I HOCH I HCOH I HCOMe I CH2OH 2- O-Acetyl-5-O-methyl-D-mannitol not 5-O-acetyl-2-O-methyI-D-mannitol 2-Carb-3. The Fischer projection of the acyclic form In this representation of a monosaccharide, the carbon chain is written vertically, with the lowest numbered carbon atom at the top. To define the stereochemistry, each carbon atom is considered in turn and placed in the plane of the paper. Neighbouring carbon atoms are below, and the H and OH groups above the plane of the paper (see below).
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`H OH ~- HPC-OH ~- H--C-OH -= H--C--OH ~ HCOH ~- H OH =- OH I [ I (a) (b) (c) (d) (e) (f) (g) Conventional representation of a carbon atom (e.g. C-2 of D-glucose) in the Fischer projection. Representation (e) will be used in general in the present document. The formula below is the Fischer projection for the acyclic form of D-glucose. The Fischer projections of the other aldoses (in the acyclic form) are given in Chart I (2-Carb-2.2). 1OH O 21 HCOH 31 HOCH 41 HCOH sI HCOH 61 CH2OH D-Glucose Note. The Fischer projection is not intended to be a true representation of conformation. 2-Carb-4. Configurational symbols and pre~es 2-Carb-4.1. Use of D and L The simplest aldose is glyceraldehyde (occasionally called glyceral [21]). It contains one centre of chirality (asymmetric carbon atom) and occurs therefore in two enantiomeric forms, called D-glyceraldehyde and L-glyceraldehyde; these are represented by the projection formulae given below. It is known that these projections correspond to the absolute configurations. The configurational symbols D and L should appear in print in small-capital roman letters (indicated in typescript by double underlining) and are linked by a hyphen to the name of the sugar. 13 CHO ...CHO ... H--(~--OH HO--C--H CH2OH CH2OH D-Glyceraldehyde 2-Carb-4.2. The configurational atom L-Glyceraldehyde A monosaccharide is assigned to the D or the L series according to the configuration at the highest-numbered centre of chirality. This asymmetrically substituted carbon atom is called the 'configurational atom'. Thus if the hydroxy group (or the oxygen bridge of the ring form; see 2-Carb-6) projects to the right in the Fischer projection, the sugar belongs to the D series and receives the prefix D-. Examples: CHO I ?HO CH20 H HOCH, HCOH CHO C=O HOCH I I I I HOCH HCOH HOCH HCOH I I I 1 HCOH HOCH HCOH HOCH I t I I HCOH HCOH HCOH HCOH I I I I CH2OH CH2OH CH2OH CH2OH D-Glucose D-Xylose D-arabino-Hex-2-ulose (D-Fructose) D Monosaccharides D-glycero-L-gulo-Heptose
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`PGR2020-00009
`Pharmacosmos A/S v. American Regent, Inc.
`Petitioner Ex. 1061 - Page 11
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`14 CHO I CHO CHzOH HOCH I [ I HOCH CHO C=O HOCH I I I I HCOH HCOH HOCH HCOH HOCH HOCH HCOH HCOH I I I I HOCH HOCH HOCH HOCH I L I I CH2OH CH2OH CH2OH CH2OH L-Glucose L-Arabinose L-xy/o-Hex-2-ulose (L-Sorbose) L Monosaccharides 2-Carb-4.3. Configurational prefixes in systematic names L-glycero-D-manno-Heptose In the systematic names of sugars or their derivatives, it is necessary to specify not only the configuration of the configurational atom but also the configurations of all CHOH groups. This is done by the appropriate configurational prefix. These prefixes are derived from the trivial names of the aldoses in Chart I (relevant portions of the structures are delineated in bold face). In monosaccharides with more than four asymmetrically substituted carbon atoms, where more than one configurational prefix is employed (see 2-Carb-8.3), each group of asymmetrically substituted atoms represented by a particular prefix has its own configurational symbol, specifying the configuration (D or L) of the highest numbered atom of the group. The configurational prefixes are printed in lower-case italic (indicated in typescript by underlining), and are preceded by either 13- or L-, as appropriate. For examples see 2-Carb-4.2 and 2-Carb-6.2 Note. In cyclic forms of sugars, the configuration at the anomeric chiral centre is defined in relation to the 'anomeric reference atom' (see 2-Carb-6.2). 2-Carb-4.4. Racemates and meso forms Racemates may be indicated by the prefix DE-. Structures that have a plane of symmetry and are therefore optically inactive (e.g. erythritol, galactitol) are called meso forms and may be given the prefix 'meso-'. 2-Carb-4.5. Optical rotation If the sign of the optical rotation under specified conditions is to be indicated, this is done by adding (+)- or (-)- before the configurational prefix. Racemic forms are indicated by (_+)-. Examples: D-Glucose or (+)-D-glucose D-Fructose or (-)-D-fructose DE-Glucose or (+)-glucose 2-Carb-5. Cyclic forms and their representation 2-Carb-5.1. Ring size Most monosaccharides exist as cyclic hemiacetals or hemiketals. Cyclic forms with a three-membered ring are called oxiroses, those with a four-membered ring oxetoses, those with a five-membered ring furanoses, with a six-membered ring pyranoses, with a seven-membered ring septanoses, with an eight-membered ring octanoses, and so on. To avoid ambiguities, the locants of the positions of ring closure may be given; the locant of the carbonyl gr