25.5: Cyclic Structures of Monosaccharides - Anomers (2023)

cyclic monosaccharide

In Sections 19-10 it was discussed that the reaction of one equivalent of an alcohol in the presence of an acid catalyst reversibly adds to aldehydes and ketones to form a hydroxyether calledHalbacetal(R₂COHOR') (hemi,Greek, half).

Molecules that have an alcohol and a carbonyl can undergo an intramolecular version of the same reaction, forming a cyclic hemiacetal.

Because sugars often contain alcohol and carbonyl functional groups, intramolecular hemiacetal formation is common in carbohydrate chemistry. Five and six member rings are preferable to other ring sizes due to their low obscuration angle and elongation. Cyclic structures of this type are called furanose (five-membered) or pyranose (six-membered), reflecting the relationship of ring size to the common heterocyclic furan and pyran compounds shown below.

Furan (5-membered ring) and Pyranian (6-membered ring) structures

Unlike most of the biochemical reactions you will see in this text, sugar cyclization reactions are not catalyzed by enzymes: they occur spontaneously and reversibly in aqueous solution. Sugars are usually shown in their open-chain form, but glucose, fructose, and other five- and six-carbon sugars readily convert between straight-chain and cyclic forms in aqueous solution. For most sugars with five and six carbon atoms, the cyclic forms dominate at equilibrium because they are more stable. The size of the cyclic hemiacetal ring that a given sugar assumes is not constant, but can vary with substituents and other structural features.

Aldohexoses normally form pyranose rings, and their pentose counterparts tend to prefer the furanose form, but there are many counterexamples. At equilibrium, less than 1% of the glucose is in the open-chain form and the remainder almost exclusively in the cyclic pyranose form. The pyranose ring is formed by the attack of the hydroxyl on carbon 5 of glucose on the aldehyde carbon (carbon #1, also known as anomeric carbon in carbohydrate terminology). The cyclic form of glucose is called glucopyranose. Note that for glucose and other aldohexoses, the hydroxyl that forms the cyclic hemiacetal is also the one that determines the D/L designation of a sugar.

Pyranose rings are often designed in a chair conformation like cyclohexane rings (section 4-6)with substituents in axial or equatorial position. Pyranose rings can even undergo ring inversion to switch between chair conformations. Usually the oxygen ring is placed to the right and back of the frame (upper right corner in the drawing). Clusters going to the right in a Fischer projection are oriented "down" in the pyranose ring, while clusters going to the left are oriented "up" in the chair frame. Also the -CH terminal₂The OH group is oriented up the pyranose ring in D sugars and down in L sugars.

When D-glucose cyclizes, it forms a 37/63 mixture of alpha and beta anomers, respectively. The beta anomer is preferred because β-D-glucopyranose is the only aldohexose that can be grown with all of its bulky substituents (-OH and -CH).₂OH) in an equatorial position, making it the most stable of the eight D-aldohexoses, probably explaining its wide distribution in nature.

It is possible to obtain a crystalline glucose sample in which all the molecules have the α structure or all have the β structure. The α form melts at 146°C and has a specific rotation of +112°, while the β form melts at 150°C and has a specific rotation of +18.7°. However, dissolution of the sample in water soon produces a mixture containing anomers and the linear chain form in dynamic equilibrium. You can start with a pure sample of crystalline glucose made up entirely of either anomer, but once the molecules dissolve in water, they open up to form the carbonyl group and then close up again to form the α or β anomer. The opening and closing are continuously repeated in a continuous interconversion between anomeric forms and are denoted asmutarotation(Latinchange, which means "change"). At equilibrium, the mixture consists of approximately 36% α-D-glucose, 64% β-D-glucose, and less than 0.02% of the open-chain aldehyde form. The observed rotation of this solution is +52.7°.

Fructose in aqueous solution forms a six-membered cyclic hemiketal called fructopyranose when the hydroxyl oxygen at carbon #6 attacks the carbon of the ketone (carbon #2, the anomeric carbon of fructose).

In this case, the β anomer is strongly favored at equilibrium with a 70:1 ratio, since the bulkier -CH₂The OH group occupies an axial position. In the figure above, note that the percentages of α and β anomers present at equilibrium do not add up to 100%. Fructose also exists in solution as a five-membered cyclic hemiketal, referred to in carbohydrate nomenclature as fructofuranose. In the formation of fructofuranose from open-chain fructose, the fifth carbon hydroxyl group attacks the ketone.

In aqueous solution, fructose then exists as an equilibrium mixture of 70% β-fructopyranose, 23% β-fructofuranose, and minor percentages of open-chain and cyclic α-anomers. The β-pyranose form of fructose is one of the sweetest compounds known and the main ingredient in high fructose corn syrup. The β-furanose form is much less sweet.

Although we have considered specific examples of glucose and fructose, other five- and six-carbon monosaccharides also exist in solution as equilibrium mixtures of open-chain and cyclic hemiacetals and hemiketals. However, shorter monosaccharides are unlikely to undergo analogous ring formation reactions due to the inherent instability of three- and four-membered rings.

Draw cyclic structures ofmonosaccharide

The cyclic forms of sugars are usually represented asHaworth projections. This convention, first proposed by English chemist Walter N. Haworth, shows molecules drawn as flat rings, with dark edges representing the side facing the viewer. The structure is simplified to show only the functional groups attached to the carbon atoms. Each group wrote toTo the rightappears on a Fischer projectiondown down)the plane of the ring on a Haworth projection and each group written on thelinksappears on a Fischer projectionabove(Above) The plane at a screening of Haworth.

Figure: Conversion of the Fischer D-glucose projection to the Haworth ß-D-glucose projection.

1. When converting a Fischer (line) projection to a Haworth projection, you must first identify the type of monosaccharide involved. If the carbohydrate is an aldohexose,PyranosRing is often used. A pyranose is a cyclic structure containing five carbon atoms and one oxygen. If the carbohydrate is a ketohexose,furanosaRing is often used. The furanose ring contains four carbon atoms and one oxygen.

2. Give the arrangement of the hydroxyl group attached to the anomeric carbon to identify the sugar as an alpha or beta anomer. The α and β anomers are determined relative to carbon 6. If the molecule is a D sugar, carbon 6 is above the plane of the ring (top) forming an L sugar, carbon 6 is below the plane of the ring (ring ). The α anomer occurs when the OH on the anomeric carbon is trans to carbon 6, and the β anomer occurs when the OH on the anomeric carbon is cis to carbon 6. If the cyclic structure contains a furanose, such carbon 1 is not included in the ring, that carbon group would be located opposite the OH group.

3. The remaining chiral centers (pyranose carbons 2, 3, and 4 or furanose carbons 3 and 4) are arranged based on the directions of the hydroxyl groups of the Fischer projection structures. Clusters to the left of the Fischer projection would point up (upper plane), while clusters to the right would point down (lower plane).

Since the Fischer projection of a given carbohydrate is always the same, the Haworth projection is essentially always the same. The only difference between the Haworth projection of the alpha or beta form of an individual carbohydrate is how the OH (and carbon 1 on the furanose ring) is arranged around the anomeric carbon to determine whether the molecule is alpha or beta.

Stability of the chair conformation in pyranose sugars.

Earlier we saw the six ring atoms of cyclic glucose drawn in two dimensions. A closer look reveals that the molecule adopts a chair-like conformation, as expected.

The conformation in which all the substituents are equatorial has the lowest energy. The two isomeric forms are indicated by the Greek letters alpha (A) and beta (B).

We haven't learned anything about stereoisomerism yet, but you can still see that the bond configuration on one carbon is different. In the alpha isomer, one of the hydroxyl groups is axial: this isomer cannot assume a chair conformation in which all non-hydrogen substituents are equatorial. The lowest energy conformation is one in which four of the five substituents are equatorial, but the presence of an axial hydroxyl group means that the alpha isomer is less stable overall than the beta isomer.

The most common form of fructose in aqueous solution is also a six-membered ring.

The lowest energy chair conformation is the one with three of the five substituents (including the bulky –CH₂OH group) in equatorial position.

6.

Credits and Attributions

• William Reusch, Professor Emeritus (michigan state u.),organic chemistry virtual book

• Basic notions of general, organic and biological chemistrypor David W Ball, John W Hill y Rhonda J Scott.