Ketoses are a special group of sugars. D-ribulose derivatives play a vital role in photosynthesis. A — Physical Chemistry — Thermodynamics Chemistry Question
Theoretical Problem 21: Carbohydrates and Acetonide Protecting Groups
Ketoses are a special group of sugars. D-ribulose derivatives play a vital role in photosynthesis. An α-methyl glycoside of D-ribulose (A) can be prepared from D-ribulose on treatment with methanol and an acid catalyst. Heating A in acetone with HCl leads to B, a propylidene derivative. Acetone forms acetals with vicinal diols, if the orientation of the two OH groups is suitable.
[VISUAL]
During the synthesis of B two possible products can form. Draw their structures. Which is the main product?
Model Answer
The formation of the 1,3-isomer is less likely (trans anellation of a 5 and 6-membered ring). The main product is the 3,4-acetonide.
[VISUAL]
B is reacted with acetic anhydride (with catalyst) to obtain C. D is formed from C on heating in dilute aqueous acid. D reacts with methanol and acid to form E. Draw the structures of C - E.
Model Answer
C is the acetylated derivative at the free C1-OH position of B (1-O-acetyl-3,4-O-isopropylidene-α-D-ribulofuranoside).
D is formed by cleaving both the acetonide group and the methyl glycoside, leaving the acetate group intact (1-O-acetyl-D-ribulose).
E is formed by glycosylation of D with methanol, yielding methyl 1-O-acetyl-D-ribulofuranoside as a mixture of α and β isomers.
[VISUAL]
Is it possible to predict the conformation around carbon atom C1 of E?
Model Answer
No. D has an unblocked glycosidic OH group, so during the synthesis of E both α and β isomers can be formed. The isomeric composition depends on the reaction conditions.
Draw the two chair conformers of 1-O-methyl-6-O-acetyl-β-D-galactose<1.5> (F). Designate the OH groups as axial (a) or equatorial (e). Mark the more stable conformer.
Model Answer
The two chair conformers of 1-O-methyl-6-O-acetyl-β-D-galactose<1.5> (F) are:
1. The 4C1-like conformer (more stable): 1-OCH3 (e), 2-OH (e), 3-OH (e), 4-OH (a), 5-CH2OAc (e). This conformer has 4 equatorial substituents and 1 axial substituent.
2. The 1C4-like conformer: 1-OCH3 (a), 2-OH (a), 3-OH (a), 4-OH (e), 5-CH2OAc (a). This conformer has 4 axial substituents and 1 equatorial substituent.
[VISUAL]
How many acetonide isomers can form from this compound? How many different chair conformers of these acetonides exist?
Model Answer
Two acetonide isomers can form: the 2,3-acetonide and the 3,4-acetonide.
Three different chair conformers of these acetonides exist in total:
- The 3,4-acetonide isomer has two different chair conformers because the cis-vicinal diol (axial-equatorial in 4C1, equatorial-axial in 1C4) can accommodate the 5-membered dioxolane ring in both chair conformations.
- The 2,3-acetonide isomer has only one chair conformer because the trans-vicinal diol (diequatorial in 4C1, diaxial in 1C4) can only form an acetonide when diequatorial. No acetonide can be formed when the neighbouring OH groups are both axial (as in the diaxial 1C4 conformer).
[VISUAL]
Draw the Haworth projection of L-galactose <1.5>.
Model Answer
The Haworth projection of L-galactopyranose (L-galactose <1.5>) is the enantiomer of D-galactopyranose:
- The six-membered pyranose ring is drawn with the oxygen atom at the top-right.
- C1 is on the right, with a wavy bond for the OH group (representing both α and β anomers).
- C2-OH points UP.
- C3-OH points DOWN.
- C4-OH points DOWN.
- C5-CH2OH points DOWN.
[VISUAL]