Table of contents

1. A Review of General Chemistry5h 5m
2. Molecular Representations1h 14m
3. Acids and Bases2h 46m
4. Alkanes and Cycloalkanes4h 17m
5. Chirality3h 39m
6. Thermodynamics and Kinetics1h 22m
7. Substitution Reactions1h 48m
8. Elimination Reactions2h 30m
9. Alkenes and Alkynes2h 9m
10. Addition Reactions3h 19m
11. Radical Reactions1h 58m
12. Alcohols, Ethers, Epoxides and Thiols2h 42m
13. Alcohols and Carbonyl Compounds2h 17m
14. Synthetic Techniques1h 26m
15. Analytical Techniques:IR, NMR, Mass Spect7h 3m
16. Conjugated Systems6h 13m
17. Ultraviolet Spectroscopy51m
18. Aromaticity2h 34m
19. Reactions of Aromatics: EAS and Beyond5h 1m
20. Phenols55m
21. Aldehydes and Ketones: Nucleophilic Addition4h 56m
22. Carboxylic Acid Derivatives: NAS2h 51m
23. The Chemistry of Thioesters, Phophate Ester and Phosphate Anhydrides1h 10m
24. Enolate Chemistry: Reactions at the Alpha-Carbon1h 53m
25. Condensation Chemistry2h 9m
26. Amines1h 43m
27. Heterocycles2h 0m
28. Carbohydrates5h 53m
29. Amino Acids4h 20m
30. Peptides and Proteins2h 42m
31. Catalysis in Organic Reactions1h 30m
32. Lipids 2h 50m
33. The Organic Chemistry of Metabolic Pathways2h 52m
34. Nucleic Acids1h 32m
35. Transition Metals6h 14m
36. Synthetic Polymers1h 49m

28. Carbohydrates

Glycoside

Organic Chemistry

28. Carbohydrates

Glycoside

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14:08 minutes

Problem 62

Textbook Question

An important protecting group developed specifically for polyhydroxy compounds like nucleosides is the tetraisopropyldisiloxanyl group, abbreviated TIPDS, that can protect two alcohol groups in a molecule.

(a) The TIPDS group is somewhat hindered around the Si atoms by the isopropyl groups. Which OH is more likely to react first with TIPDS chloride? Show the product with the TIPDS group on one oxygen.
(b) Once the TIPDS group is attached at the first oxygen, it reaches around to the next closest oxygen. Show the final product with two oxygens protected.
(c) The unprotected hydroxy group can now undergo reactions without affecting the protected oxygens. Show the product after the protected nucleoside from (b) is treated with tosyl chloride and pyridine, followed by NaBr, ending with deprotection with Bu₄NF.

Verified step by step guidance

Step 1: Analyze the structure of TIPDS chloride and the nucleoside. TIPDS chloride contains two reactive Si-Cl bonds, and the nucleoside has multiple hydroxyl (-OH) groups. The steric hindrance around the Si atoms due to the isopropyl groups makes TIPDS chloride selective in its reaction with hydroxyl groups.

Step 2: Identify the hydroxyl group most likely to react first. The hydroxyl group at the 5' position (CH2OH) is less sterically hindered compared to the other hydroxyl groups on the nucleoside. This makes it the most likely candidate for the initial reaction with TIPDS chloride.

Step 3: Show the product after the first reaction. The TIPDS group will attach to the 5' hydroxyl group, forming a silyl ether bond. The structure will now have the TIPDS group protecting the 5' oxygen.

Step 4: Consider the second reaction. Once the TIPDS group is attached to the first oxygen, it can reach around to the next closest hydroxyl group due to its flexible Si-O bond. The 3' hydroxyl group is the next closest and will react to form a second silyl ether bond, resulting in both the 5' and 3' oxygens being protected by the TIPDS group.

Step 5: Address the final part of the problem. The unprotected hydroxyl group (likely at the 2' position) can now undergo reactions. Treating the protected nucleoside with tosyl chloride and pyridine will convert the unprotected hydroxyl group into a tosylate. Subsequent reaction with NaBr will replace the tosyl group with a bromine atom. Finally, deprotection with Bu4NF will remove the TIPDS group, restoring the original hydroxyl groups at the 5' and 3' positions.

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Key Concepts

Here are the essential concepts you must grasp in order to answer the question correctly.

Protecting Groups in Organic Chemistry

Protecting groups are temporary modifications used to shield reactive functional groups during chemical reactions. In the context of polyhydroxy compounds, such as nucleosides, protecting groups like the tetraisopropyldisiloxanyl (TIPDS) group prevent unwanted reactions at hydroxyl (-OH) sites, allowing for selective functionalization of other parts of the molecule.

Reactivity of Alcohols

Alcohols are characterized by their hydroxyl (-OH) groups, which can act as nucleophiles in chemical reactions. The reactivity of alcohols can vary based on steric hindrance and electronic effects. In the case of TIPDS protection, the steric bulk of the isopropyl groups around the silicon atoms influences which hydroxyl group will react first with TIPDS chloride, typically favoring the less hindered alcohol.

Deprotection Strategies

Deprotection is the process of removing a protecting group to restore the original functional group. In this scenario, after the nucleoside is treated with tosyl chloride and pyridine, the protected hydroxyl groups remain intact while the unprotected hydroxyl can undergo further reactions. The final step involves using Bu4NF to selectively remove the TIPDS group, allowing for the desired functionalization of the nucleoside.

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Related Practice

Textbook Question

Draw the following sugar derivatives.

(a) methyl β-D-glucopyranoside

(b) 2,3,4,6-tetra-O-methyl-D-mannopyranose

(d) methyl 2,3,4,6-tetra-O-methyl-β-D-galactopyranoside

Name the following:

Name the following:

Some protecting groups can block two OH groups of a carbohydrate at the same time. One such group is shown here, protecting the 4-OH and 6-OH groups of β-d-glucose.

(a) What type of functional group is involved in this blocking group?

(b) What did glucose react with to form this protected compound?

(c) When this blocking group is added to glucose, a new chiral center is formed. Where is it? Draw the stereoisomer that has the other configuration at this chiral center. What is the relationship between these two stereoisomers of the protected compound?

(d) Which of the two stereoisomers in part (c) do you expect to be the major product? Why?

Textbook Question

Show the products that result from hydrolysis of amygdalin in dilute acid. Can you suggest why amygdalin might be toxic to tumor (and possibly other) cells?

Textbook Question

The mechanism of glycoside formation is the same as the second part of the mechanism for acetal formation. Propose a mechanism for the formation of methyl β-D-glucopyranoside.

Textbook Question

Treatment of either anomer of fructose with excess ethanol in the presence of a trace of HCl gives a mixture of the α and β anomers of ethyl-D-fructofuranoside. Draw the starting materials, reagents, and products for this reaction. Circle the aglycone in each product.

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