I am currently using benzoyl anhydride to do the protection but the reaction is proceeding way too slow and may not even be proceeding to 100% conversion. So I am sourcing for alternatives. Benzoyl chloride was suggested but I am afraid it would end up protecting the 3'OH as well. I am using the product for further synthesis of phosphoramidites.
Hi Geraldine,
if you use PhCOCl, you have to use a base as well to let the reaction go. The alcohol may react mostly as an anion, since the nucleophilicity of the the neutral -OH is quite low, whereas the amine reacts as a neutral molecule. Out of logic, it suggests using a weak base to avoid the alcohol deprotonation. I would try a reaction with PhCOCl in the presence of 1,2 eq of pyridine or N,N-dimethylaniline in DCM.
Hi Mark, this looks like a good strategy. Thank you very much for the recommendation. May I check with you, is there a reason why cytidine is more tricky to protect as compared to adenosine? The amine in both are relatively low in nucleophilicity?
Yes and I believe that one reason my reaction with benzoic anhydride is taking very long could be due to the presence of the iodine at C5.
Hi Andrei, I am already doing my reaction with benzoic anhydride in either dry DMF or pyridine. I still feel that the side reaction of the 3'OH benzoylation would be a problem.
Hi Mark, I see. It's about 2 months for me into nucleic acid chemistry and I have been working towards making phosphoramidites. I have read literature stating that OH and NH2 protections are generally simple. My first experience of DMF-DMA exocyclic amine protection and DMT protection was a manageable one but I would not really say that the synthesis is easy at all. I believe you are well-experienced in this area and I would gladly appreciate an advice or two from you (if you do have any enlightenment from your experiences) on the nucleoside synthesis work.
Geraldine,
For your compound, is it possible to use a different protective group instead of the benzoyl?
Dear Jacek, I have previously protected it with DMF (using DMF-DMA reagent) but the protecting group is very labile and deemed not suitable for it to be part of the phosphoramidite that I will be making.
... I meant something still different. I understand that that would not be a good option, thanks.
I believe acetyl may be an alternative? although it is probably labile too..
Just an update here, I have stopped my reaction and decided I will give the transient protection that Mark has mentioned a try. I believe it's a very tricky procedure. hope to have good news nonetheless!
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