Hallo,
I would like to raise a topic on the synthesis of antibiotics.
As we know, cefepime is an antibiotic of the fourth generation which has a structure almost similar to that of cefotaxime (an antibiotic of the third generation) except the substituent at the 3-rd position of the cephem nuclei.
My question is that, are there any ways to directly convert cefatoxime into cefepime? Well, as for me, I am thinking of protecting the amino and carbocyclic groups and treat with TMS-I then deprotect and treat with N-methylpyrrolidine (see the scheme attached). Do you think that it may work or do you have any ideas?
Thank you for suggestions.
Regards,
CPC
Cefotaxime to Cefepime
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Let me start by saying that I'm only a high school chemistry student. The only insight I can offer will be purely on the theoretical level and will mainly be from "The Organic Chemistry of Drug Synthesis" by D. Lednicer.
As a note, I cannot see your attachments for some reason.
For what it's worth, I doubt it would be as simple as throwing up TMS protecting groups and treating with N-methylpyrrolidine, as the implication is formation of a C-N bond forming a quaternary ammonium spontaneously.
Lednicer suggests a synthesis for cefepime that involves, instead of cefotaxime, a species with chlorine at position three instead of the acetyl that cefatoxime has. (Shown below) If there were a way to replace the acetyl group of cefatoxime with a chloro group, it would be as simple as adding N-methylpyrrolidine and removing the protecting groups.
[/img]
As a note, I cannot see your attachments for some reason.
For what it's worth, I doubt it would be as simple as throwing up TMS protecting groups and treating with N-methylpyrrolidine, as the implication is formation of a C-N bond forming a quaternary ammonium spontaneously.
Lednicer suggests a synthesis for cefepime that involves, instead of cefotaxime, a species with chlorine at position three instead of the acetyl that cefatoxime has. (Shown below) If there were a way to replace the acetyl group of cefatoxime with a chloro group, it would be as simple as adding N-methylpyrrolidine and removing the protecting groups.
[/img]Thank you
Dear Zedekiah,
Oh, thank you very much for your dícussion. I have got a problem with uploading an image of the scheme of the reactions. Could you show me how to do that as I have seen you could put the image into your discussion. I wanted to attach a PDF file but I could not find the function.
Could you tell me in which volum of "the Organic Chemistry of Drug Synthesis" by Lednicer have you got the suggestion for a synthesis of cefepime?
In principle, the ester group of cefotaxime can be replaced by I when treated with TMS-I. I am still wondering whether we should protect the amino and the carboxyclic groups.
I appreciate your argument very much.
Sincerely,
CPC
Oh, thank you very much for your dícussion. I have got a problem with uploading an image of the scheme of the reactions. Could you show me how to do that as I have seen you could put the image into your discussion. I wanted to attach a PDF file but I could not find the function.
Could you tell me in which volum of "the Organic Chemistry of Drug Synthesis" by Lednicer have you got the suggestion for a synthesis of cefepime?
In principle, the ester group of cefotaxime can be replaced by I when treated with TMS-I. I am still wondering whether we should protect the amino and the carboxyclic groups.
I appreciate your argument very much.
Sincerely,
CPC
I don't believe there is a method for attaching pdf files, perhaps conversion to an image, uploading to a site and then using the ![Image]()
command will do?
Ah! I was unaware the ester would act in such a fashion. The book does state, in both cases, the carboxylic and primary amine group needed protection when modifying the C-3 position.
The only reagent named in volume 3 was "...the primary amino group is then blocked with chloroacetyl chloride..."
It logically follows that after protecting the carboxylic and amine groups, replacing the C-3 position with I and treating with N-methylpyrrolidine should convert cefatoxime to cefepime.
Volume 3, page 216 contains additional information about cefatoxime.
Volume 4, page 186-187 contains a brief section about cefepime synthesis.
Thanks for bringing this topic up to discussion,
Zedekiah
Ah! I was unaware the ester would act in such a fashion. The book does state, in both cases, the carboxylic and primary amine group needed protection when modifying the C-3 position.
The only reagent named in volume 3 was "...the primary amino group is then blocked with chloroacetyl chloride..."
It logically follows that after protecting the carboxylic and amine groups, replacing the C-3 position with I and treating with N-methylpyrrolidine should convert cefatoxime to cefepime.
Volume 3, page 216 contains additional information about cefatoxime.
Volume 4, page 186-187 contains a brief section about cefepime synthesis.
Thanks for bringing this topic up to discussion,
Zedekiah
Dear
thank you for your discussion. I hope that I can get suggestions from you from time to time.
I have found a patent disclosing a way to convert cefotaxime into cefepime. The general ideas are quite similar to what we have agreed.
I give you the address of the patent in case you may be interested in.
WO2004092183A2.
Best regards,
CPC
thank you for your discussion. I hope that I can get suggestions from you from time to time.
I have found a patent disclosing a way to convert cefotaxime into cefepime. The general ideas are quite similar to what we have agreed.
I give you the address of the patent in case you may be interested in.
WO2004092183A2.
Best regards,
CPC