Question

L-Gulose can be prepared from D-glucose by a route that begins with oxidation to D-glucaric acid, which cyclizes to form two six-memberedring lactones. Separating the lactones and treating them with sodium amalgam, \(\mathrm{Na}(\mathrm{Hg})\), reduces the \(-\mathrm{CO}_{2} \mathrm{H}\) group to a primary alcohol and the lactone to an aldehyde, giving D-glucose and L-gulose. What are the structures of the two lactones, and which one is reduced to L-gulose?

Short answer

The δ-lactone is reduced to L-gulose.

Step-by-step solution

Understanding the Conversion

The reaction sequence involves converting D-glucose to D-glucaric acid. D-glucaric acid then cyclizes to form two lactones. Separating these lactones and treating them with sodium amalgam reduces the lactone ring's carbonyl to an aldehyde while the \[-\mathrm{CO}_{2} \mathrm{H}\] group is reduced to a primary alcohol, eventually producing D-glucose and L-gulose.

Formation of D-Glucaric Acid

D-glucose is oxidized to D-glucaric acid. This step involves introducing carboxylic acid groups at specific positions, maintaining the stereochemistry derived from D-glucose. D-glucaric acid can be represented as: \[\text{C}-\text{(C(OH)-COOH)-(CHOH)_{3}-COOH}\].

Cyclization to Form Lactones

D-glucaric acid undergoes cyclization to form two possible lactones. The cyclization typically occurs at the positions surrounding the carboxylic acids, forming a cyclic ester, essentially a lactone. The two possible six-membered ring lactones are 'γ-lactone' and 'δ-lactone'.

Identifying the Lactones' Structures

The two lactones form from a reaction between hydroxyl groups and the carboxylic acids in D-glucaric acid. A six-membered lactone structure will form at two positions around one of the carboxylic acids: one with the carboxylic acid of carbon 1 and a hydroxyl of carbon 5 (γ-lactone), and one with the acid of carbon 1 and hydroxyl on carbon 6 (δ-lactone).

Reduction with Sodium Amalgam

Each lactone undergoes reduction. When treated with sodium amalgam, the γ-lactone—which is related structurally to D-glucose—is reduced to reform D-glucose. The δ-lactone side of D-glucaric acid is reduced to yield aldehyde and primary alcohol products, giving rise to L-gulose.

Identifying the L-Gulose Lactone

Of the two lactones, the δ-lactone of D-glucaric acid features a ring closed at position 6, making it prone to reduction to an aldehyde at the original carboxyl group in its conversion to L-gulose.

Key concepts

D-glucose

D-glucose is a naturally occurring sugar, also known as dextrose. It's a monosaccharide, which means it is an essential building block of more complex carbohydrates. In the body, it is a primary energy source for cells.

Chemically, D-glucose is represented by the formula \( C_6H_{12}O_6 \), indicating it has six carbon atoms, twelve hydrogen atoms, and six oxygen atoms. Its structure is notably recognized in its cyclic form, where the first carbon (the anomeric carbon) forms a hemiacetal linkage with the hydroxyl group on either the fourth or fifth carbon. This cyclic formation accounts for two distinct forms: the alpha and beta anomers of glucose.

D-glucose is important in biological pathways like glycolysis, where it is converted into pyruvate, releasing energy stored in its bonds. It's also central in various chemical reactions, including those involving oxidation, such as the conversion to D-glucaric acid, which is a crucial step in synthesizing other sugars like L-gulose.

L-gulose

L-gulose is an epimer of D-glucose, meaning it shares the same molecular formula as D-glucose but differs in the spatial arrangement around one specific carbon atom. This difference is crucial in biochemistry as it affects how the sugar interacts with other molecules and enzymes.

In L-gulose, the difference lies at the fourth carbon atom where the hydroxyl group is oriented differently compared to D-glucose. Despite these differences in spatial configuration, L-gulose doesn't naturally occur in significant amounts in nature, making its synthesis and study mainly a focus in the field of organic chemistry.

The transformation of D-glucose into L-gulose involves several steps, as outlined in the exercise. Initially, the D-glucose is oxidized to form D-glucaric acid. Then, through cyclization, two lactones form, and through reduction with sodium amalgam, one of these lactones is converted into L-gulose, showcasing the power of chemical reactions in modifying sugar structure.

Reduction with Sodium Amalgam

Reduction with sodium amalgam, \( ext{Na(Hg)} \), is a chemical process used to convert specific functional groups in organic compounds to less oxidized forms. It's a method employed to selectively reduce a compound, especially in the context of transforming sugars and other complex molecules.

Sodium amalgam, a mixture of sodium and mercury, is used for reducing the carbonyl group in lactones, which are cyclic esters formed by the reaction of the hydroxyl and carboxyl groups in a sugar compound like D-glucaric acid. In the exercise at hand, the sodium amalgam specifically reduces the lactone originally formed from D-glucose to an aldehyde. This converts the carboxylic acid to a primary alcohol in L-gulose, allowing for the structural transformation to take place.

It’s a preferred method in sugar reduction chemistry because it offers controlled reduction conditions, minimizing the risk of over-reduction or damaging sensitive molecules.