Fructopyranose conformation

Crystallographic data have not yet been reported for one of the four hexuloses, namely, D- or L-psicose, not yet crystallized. Preliminary results are available for /3-D-fructopyranose.18a As expected, the sugar has the 1C (d) conformation. The hemiacetal group on C-2 is not bound to a hydrogen atom, whereas 0-6 is linked to two hydrogen atoms. 

In the crystalline state -D-fructopyranose (5) possesses the 1C(d) conformation (13), and it is clear that it retains this conformation in solu-... 

Figure 3. Hydroxyl PMR signals for p-o-fructopyranose (5) (upper left) and ct-L-gala-heptulose (6) (lower left) in methyl sulfoxide-dtf. 13C NMR spectra of 5 and 6 (in water). The diagonal line relating the 13C-6 resonances of 5 and 6 reflects the large downfield shift attributable to replacement of one H-6 with the 7-carbinol group. 13C chemical shifts for a- and B-o-arabinopyranose (a and b, respectively) (10, 11) are inserted to illustrate the close conformational affinity between 5 and / -, though not a-, d-arabinose (ppm relative to downfield...

In the synthesis of D-tagatose from the more common D-fructose, 1-O-benzoyl-2,3-O-isopropylidene-P-D-fructopyranose afforded two products identified as l-O-benzoyl-5-0-benzyl-2,3-0-isopropylidene-P-D-fructopyranose (97%) and its 4-O-benzyl isomer (2.8%). The skew-boat 6S4(D) conformation with an oxygen atom at C-5 adopting a quasi-equatorial position is responsible for the unexpected regioselectivity observed [136]. Conformational equilibria may also be a reason for the non-exclusive, though preferential substitution at 0-3 of benzyl 4-0-benzyl-6-deoxy-a-L-talopyranoside (9) [142]. Even in this case, however, no tri-O-benzyl derivative was formed and no starting material 9 remained, the total isolated yield of 10 and 11 being 87%. 

Table 1.2 displays the tautomeric composition of pentoses and hexoses in aqueous solution as well as 1-deoxy fructose 1.20, and fructofuranose-l,6-diphosphate 1.21. The predominance of pyranoses is observed. The galactofuranoses 1.22 are relatively more stable than the glucofuranoses 1.23, perhaps due to the trans arrangement of the hydroxyl at C-3 and the side chain in the former. We also see that there are ten times as many jS- as there are a-pyranoses in the fructose solutions. At this point we are jumping ahead to Chapter 2, which is devoted to problems of conformation. We can draw /To-fructopyranose as confonnation 1.24 where only one unfavorable interaction takes place between H-3 and OH-5. The exchange of substituents at C-2 leads to an eminently unfavorable conformation which shifts to 1.25, the lesser of two evils, but where strong 1,3-diaxial interactions remain. 

Figure 1.39 Conformational extremes of a-D-fructopyranose (left) and /3-D-fructofuranose (right). Anomeric Carbon Cl is on right-hand side by convention.

Although there is some uncertainty as to the conformational effect of one cis-fiised, 5-membered acetal ring, evidence from both i.r.-and n.m.r.-spectral studies clearly indicates that the presence of two such cis-fiised rings forces the cyclohexane or pyranoid ring to adopt a skew conformation. Thus, the pyranoid ring in derivatives of 1,2 3,4-di-0-isopropylidene-j3-L-arabinose and -a-D-galactopyranose (34), and of 2,3 4,5-di-0-isopropylidene-/3-D-fructopyranose (35), and the... 

At mutarotational equilibrium in water, D-fructose (51) exists preponderantly as the j8-D-pyranose anomer in the 1C(d) conformation. A 1,2-alkylidene acetal (52) is formed in the same way as for L-sorbose, but this monoacetal has cts-disposed hydroxyl groups at C-4 and C-5 that react readily, forming a l,2 4,5-di-0-alkylidene-)8-D-fructopyranose (53). No evidence is available to indicate that the 1,2-alkylidene acetal might rearrange to a 1,3-alkylidene acetal, and it is to be expected that the activation energy for this isomerization would exceed that for formation of an acetal at 0-4 and 0-5. 

Di-0-isopropylidene-jS-D-fructopyranose (2), an example of the general structure 54, appears from proton magnetic resonance data to adopt the SJ conformation. " This conformation is in accord with those proposed for other diacetals in which the parent sugar has... 

A second type of monoacetal is known for D-fructopyranose, namely, the 2,3-O-alkylidene-jS-D-fructopyranose structure (54). A distorted CJ(d) conformation is indicated for the isopropylidene acetal 5 (54, R = R = Me), from proton magnetic resonance data. Undoubtedly, this conformation is not favored for /3-D-fructopyranose itself, because of unfavorable steric and anomeric effects (see This Volume, Chapter 2). It is unreasonable to expect that monoacetal 54 will be formed directly from jS-D-fructopyranose, because a much more favored pathway, leading to monoacetal 52, is available. This consideration precludes a second, possible avenue to diacetal 55, namely, alkylidenation of 0-4 and 0-5 of 54. Monoacetals of type 54 can be prepared by partial hydrolysis of diacetals of type 55. 

Among the monoacetals, those containing a 1,2-O-isopropylidene ring, namely, 3,4,5-tri-0-acetyl-l,2-0-isopropylidene-a-L-sorbopyra-nose (64), 3,4,5-tri-0-acetyl-l,2-0-isopropylidene-j8-D-fructopyranose (65), and 4,5-di-O-acetyl- l,2-0-isopropylidene-3-0-methyl-j8-D-fructo-pyranose (66), have been assigned the JC(d) conformations depicted. ... 

Figure 3 Ball-and-stick model of the preferred conformation of p-L-fructopyranose (a) and a-D-galactopyranose (b). The OH groups that react with the boronic acid are represented in black. The hydroxy methylene groups which influence the shape are hatched (adapted from Ref 42).

D-Fmctose (CgHi206) is a six-carbon polyhydroxyketone (Fig. 43a). Although ketohexoses such as fructose can exhibit a linear form, o-fructose rapidly cyclizes in aqueous solution to form mixtures of pyranose and furanose forms [246, 247]. The cyclization reaction converts C2 in a chiral carbon, yielding two enantiomers designated a and p (Fig. 43b). For o-fructose, the equilibrium concentrations in water are around 82% of pyranose forms and 12% of furanose forms [271]. However, in its crystalline form, the unique species found is the p-o-fructopyranose [272,273]. Besides other higher energy forms, pyranoses preferably adopt a rigid chair backbone with the conformations 2 and 5 shown in Fig. 43c. 

The extent to which the sulphur atom in the ring of the anomers of 5-thio-D-xylopyranose and 6-thio-D-fructopyranose distorts the conventional chair conformation of their oxygenated counterparts has been determined by H- and C-n.m.r. spectroscopy. The distortion was found to be more pronounced in the -anomers. 

P-o-fructopyranose 4CI conformation showing the 1,2,6-glucophore with the methylene group at C-6... 

Conformational analyses by n.m.r. and computational methods have been reported for the following compounds l,2-anhydro-3,4,6-tri-0-benzyl-P-D-talopyranose, anhydro sugars 13 and similar hexopyranose derivatives, methyl 3,4-0-isopropylidene-a- and P-D-galactopyranoside and their di-O-acetates and di-O-methyl ethers, 3,4-0-(/ )-benzylidene-D-ribono-1,5-lactone (see Chapter 6), and 6-deoxy-6-phosphonoyl-D-fructopyranoses (see Chapter 17 for synthesis). D-Glucospyranosylamine, its tetra-O-acetate and 4,6-0-benzylidene acetal and several N-acylated derivatives, together with D-[l- C]glucopyranosylamine, have been used in a conformational study by n.m.r. spectroscopy aimed at probing the existence of the reverse anomeric effect. ... 

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