Preliminary Carbohydrate Protection

In my relatively limited studies of carbohydrates, I've gotten to know a fair bit about these cyclic buggers.

When dealing with carbohydrates, a fair bit of it involves selectively protecting the various substituents stemming from the cyclic carbon backbone.

Why bother? Well, it's because when you're making your own carbohydrates you're interested in coupling specific substituents with other carbohydrates. The only way you can achieve specificity in your coupling reactions is with protection.

So, I'm going to list the most important carbohydrate protective methods I've learned in my CHM347 class:

Acetylation
There are three ways you can go about acylating any available OH substituents on your carbohydrate.

1. Acetic Anhydride & Pyridine
2. Acetic Anhydride & Sodium Acetate @ 100C
3. Acetic Anhydride & ZnCl2
Deprotection: Zemplen Degredation -- NaOMe / HOMe

Why are there so many methods: I might want to acylate some free OH groups while preserving my protection at another site. A lot of protection chemistry involves versatility because, well, you need it. Depending on what the carbohydrate of interest has elsewhere, I might selectively pick one of the three techniques available to me.


Fischer Glycosidation
1. MeOH in acidic conditions (dry - anhydrous - hydrochloric acid)
This method specifically protects the anomeric (C1) hydroxy group of the carbohydrate.
Deprotection: Acid


Ether Protection
Ethers are good protecting groups because they use sterics. Additionally, there are different types of ethers, each with unique methods for deprotection.

1. NaH & BnBr
This converts all open OH groups into "OBn".
Deprotection: Catalytic Hydrogenation (H2 Pd/C) -- good if you've got other groups that are not sensitive to catalytic hydrogenation..

2. Ph3CCl (Trityl Chloride) 
This reagent selectively protects the free OH of the 6th most accessible carbon atom of the carbohydrate.
Deprotection: Mild acid (AcOH)

3. TMSCl (Trimethyl Silyl Chloride) 
Converts all available OH groups into "OTMS".
Deprotection: TBAF or acid

4. TBDMSCl (T-butyl Dimethyl Silyl Chloride)
Much like TMSCl, but with more steric hindrance provided. As such, this protecting method is also selective for the OH on the most accessible 6th carbon of the carbohydrate.
Deprotection: TBAF or acid


Ester Protection
There are two ways to protect carbohydrates through esterification.

1. BzCl (Ph-CO-Cl)
This method protects every free OH group on the carbohydrate, since it is a reasonably small protecting group.
Deprotection: Zemplen Degredation (see above) or acid.

2. TsCl (Tosyl Chloride) + Pyridine 
TsCl is a bulky protecting group, and as such, it is selective for the most accessible 6th carbon of the carbohydrate.
Deprotection: Acid

---
The next post: A more complicated approach to selectively protecting more than one OH group in one step.