JO URNAL OF RESEARCH of the Nationa l Bureau of Standards-A. Physics and Chemistry Vol. 64A, No.2, March- April 1960 Conformations of the Pyranoid Sugars. I. Classification of Conformers Horace S. Isbell and R. Stuart Tipson (August 11, 1959) An impro'.'ed system is presented for indi catin g t he principal co nfor mations of pyranoid sugars and ~ e n vat l v cs, b~ attachin g two symbols to t he systematic na me. The fi,"st symbol shows t he kllld of p yranold rlll g; for example, B = a boat, C = t he chair, and S = a skew for m. (The t hree .boat and six skew rings are dist in guished by subscript numerals referring to exopla nar nng-atoms.) The second sy mbol differentiates between t wo conformat ions t hat have t he sa me type of ring, by describin g as A or E t he axial or equatorial character of t he referen.ce group at a select ed ring-atom. It the anomeric group is not quasi, t he a anomeric group IS used as the reference group . For suga rs and derivatives having a quasi anomeric group, a nd for relatives lacking an a nomeri c group, t he A or E classifi cation is based on t he reference group at t he lowest numbered , nonq uasi, asymmetri c ring-atom. 1. Introduction and a quasi bond, at about 55 ° Lo the plane. Qu asi bonds occur in pairs and are cq ually inclined Lo the Conformation , or molecular shape, is one of the plane of the ring ; they are not presen t in the boat and most importan t proper ties of the sugars and relatcd chair forms. compounds. Consideration of the shape of a The projecting bonds of the ring atoms at the ends molecule and of how the various atoms and groups of the boat forms are not truly axial or equatorial ; in it are ori en ted with respect to one another leads they have been called [8] "flagpole" (fp) and "bow­ to a bet ter understanding and interpretation of the sprit" (bs) , re pectively. (The terms enclo and exo reactions of the compound. describe them more precisely, but, for the classifica­ The term "conformation" was inLroduced into tion presented here, they will be regarded as being organic chemistry by H awor th [1] I , to describe the a:-..'ial and equatorial, respectively .) various shapes that cer tain molecules may assume. Although the importance of pyranoid conforma­ Conformations have been defined by Klyne [2] as Lions has bee n recognized for many years, their "the differenL arrangemen ts in space of the a toms nomenclature ha been inadequate. For lack of un­ in a single classical organic structure (config LlTation ), ambiguous conven tions, confusion has arisen in the arrangement being produced by the rotation or applying the symbols used. twisting (but not breaking) of bonds." Classification of conformations necessarily involves In contrast, the configuration of a compound is consideration of configm aLion. f its unique spatial arrangemen t of the atoms in the compound, such that no other arrangement of these 2 . Naming of Anomers atoms is superimposable thereon to give complete r correspondence, regardless of the conformation. J! .ormation of an anomeric ring-form from an open­ I Consequently, two compounds having different con­ cham sugar creates a new asymmetric cen ter at figurations may exist in the same general conforma­ the reducing carbon atom ; the resulting isomers tion; and the same compound (one configuration) (anomers) are designated a and fl . Anomers are may exist in different conformations. named from the relationship of the configmation at If four atoms of the pyranoid ring are coplanar the anomeric carbon atom to the configmation of a and the other two ring-atoms are para to each other, reference carbon atom of the chain of the acyclic the latter atoms may lie on the same side (cis) or on monosaccharide. If the chain has less than five opposite sides (trans) of the plane [3]. These two asymmetric carbon atoms, the reference atom is the kinds of ring have been termed " boat" and "chair," highest-numbered, asymmetric carbon atom. If the acyclic chain has more than four asymmetric carbon ) respectively. Atoms and groups are attached to ring atoms by atoms, the reference atom is the highes t-numbered bonds which may differ as regards their angle to the asymmetric carbon atom in the group of four asym­ plane of the ring (or a parallel plane) . Sueh bonds metric carbon atoms next to the functional group. [4 , 5] are designated a",'ial (a) [6], equatorial (e), and The anomer having the same configurations at the quasi (q) [7]. An axial bond lies nearly perpendicular anomeric carbon atom and the reference carbon atom to the plane; an equatorial bond, nearly in the plane; i ~ named a; the' anomer having opposite configura­ tlOns at the two atoms is named fl . The a - L isomer is the mirror image of the a-D isomer, and the fl-L 1 "Figures in brackets iudicate the literature references at the end of this paper. isomer is the mirror image of the fl-D isomer. 171 Enantiomorphic sugars are classifi ed into two ~o nfi g u ra­ tions mentioned the form in which all the ring tional series, respectively designated D and L, accordlllg ~o the atom's are coplanar, and depicted four ring sk eletons configuration of t he reference carbon atom. In the ~ I sc h e r projection formula, the h ydroxyl group 0!l t!le anomen c .car­ for the aldohexopyranoses, as in I - IV. H e noted that bon atom of t he a anomers (D a nd L series) lI es 111 the same cltrec­ tion as t he h ydroxyl group on t heir referen?e carbon ~tom, i.e. to the right in the D seri es and t.o t he left 111 the L sen es. ~ .. Although the F ischer projection formulas indicate the con­ ~ 6 fi guration at each asymmetric carbon ~tom, they do not sh?w d3 2 I 3 5 ~~4 6 2 5 6 the positions assumed by t he atoms In space. P erspectIV e pyranoid formulas, originated by Drew and Haworth [9], do, II m however approximately depict the positions (in a planar co n­ formatio'n) of all t he atoms in the molecule with respect to t he II and III " furnish two models for D-glucose and plane of t he ring. On closing the pyranoid 2 ring, carbon atom 5 of t he open-chain sugar is rotated about its bond to car.bon two for L-01 ucose," and that there are six boat forms atom 4, so as to bring the ring-forming hydroxyl !froup m to for D-glu;ose (and six for L-glu cose) , "making a position for ring closure. Wi th an aldope~~ t o~e, turmng; ?arbon total of sL"Xteen possible arrangements for D- and atom. 5 in this manner merely causes a shIft 111 the pOSitIOns of L-glucose." the attached hydrogen atoms. With an aldohexo~e). so turning carbon atom 5 (to close t he ring) causes t he 5-t.:-(hydroxy­ At the time of the monumental work of Haworth methyl) group t o assume a defini te position wi th respect to t he and coworkers, the siz e, as well as the shape, of the plane of t he ri ng. 'When t he ring is viewed in the manner ring in the fTee sugaTs was uncertain [14, 15] . In shown, t he 5-C-(hydroxymethyl) group of t he D-hexopyranose order to ascertain whether the pyranoid structures li es above the plane of t he ring and that of t he L-hexopyranose li es below it. For the aldohexopyranoses, t he a anomeri c group assiglled (by methylation procedures) to " normal" is trans to the hydroxymethyl group, and the {3 anomeric m ethyl glycosides apply to the corresponding free group is cis. For t he aldopentopyranoses, t he a anomel'l c sugars, a study of t he mutarotation and oxidation group is cis to t he hydroxyl group at carbon atom 4 a nd the reactions of aldoses was made by I sb ell and co­ (J anomeric group is trans. workers [16, 17, 18]. The ,vorle had its origin in the observation of Isb ell and Hudson [16] that aldoses H can be oxidized by bromine to lac tones without I I I I cleavage and re10Tming of the ring. I t was found HO~CG>9- y - y - y®~H that the fr ee sugars, with few exceptions, give 1,5- HO 0 lactones and have the pyranose structm e, Although consider able variation in the r eactivity D-A ldohexose skeleton a -D -A l do h ex opynmo ~e skeleton of the individual sugars with bromine was noted, the most stril,ing difl'erence was observed for the r eac­ u tivity of the a and (3 anomers of the same sugar [19]. HO 0 It was reasoned that the differ ence in r eactivity (5) I I I I ",II S ariscs from an important structural differ en ce in the HOH C - C - C - C -C ~C H OH.: 2 I I I I HO 0 two, and that, if the pyranoid sugars have strainl ess H G ring-structures, such as Hawor th had s u.gg e~ted 1 H earli er, the a and (3 hydroA'Y1 groups must be mclmed at different angles to the ring and ther efore react at L-Aldohexose skeleton a-L-Aldohexopyranose s keleton differ ent rates.