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Topic: Synthesis of N-Acyl-N,O-alcohol  (Read 1812 times)

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Offline Bertrand

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Re: Synthesis of N-Acyl-N,O-alcohol
« Reply #15 on: January 09, 2020, 02:48:17 AM »
My target compound is a modified structure of the isolated compound 4 of this paper https://doi.org/10.1016/j.bbrc.2016.09.041.
Please, I need your help to find out a good synthetic route of compound 4 of this paper https://doi.org/10.1016/j.bbrc.2016.09.041

Thanks in advance

Offline rolnor

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Re: Synthesis of N-Acyl-N,O-alcohol
« Reply #16 on: January 09, 2020, 02:41:53 PM »
I think its not easy to make it, the molecule has more than one nitrogen that is more or less nucleophilic that can react with the aldehyde. The hemiaminal will probably be sensitive. Do you have any thoughts?

Offline Bertrand

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Re: Synthesis of N-Acyl-N,O-alcohol
« Reply #17 on: January 09, 2020, 03:04:15 PM »
I have the same thoughts. The major issue will probably be making the hemiaminal and attach the thiol group (starting from carbon 7 to the thiol group)

I am still searching for how to make it. Please, all your suggestions will, of course, be welcome.

Offline rolnor

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Re: Synthesis of N-Acyl-N,O-alcohol
« Reply #18 on: January 09, 2020, 05:20:54 PM »
I have the same thoughts. The major issue will probably be making the hemiaminal and attach the thiol group (starting from carbon 7 to the thiol group)

I am still searching for how to make it. Please, all your suggestions will, of course, be welcome.

I think a good start would be to use 2-azidobenzamide and try to add it to the thiolaldehyde. The azido group can be reduced with PPh3 to amine after this. I dont think you can have a Boc-protected amino acid, the deprotection will cleave the hemiaminal. Maybe a Fmoc is better, the hemiaminal should be stable to base like piperidine wich is used for Fmoc-deprotection. The first step with the azidobenzamide reacting with thiolaldehyde would be great to study directly with NMR, the aldehyde should dissapear and you get something close ta a acetal-peak. If you run TLC then use a system with base like triethylamine or use aluminunoxide instead if silica wich is acidic to avoid hydrolysis of the hemiaminal. One bad thing is the thiol wich smells veeeery bad i guess.
« Last Edit: January 09, 2020, 05:35:46 PM by rolnor »

Offline Bertrand

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Re: Synthesis of N-Acyl-N,O-alcohol
« Reply #19 on: January 10, 2020, 02:13:05 AM »
Thank you very much.
 
I think instead of using the smelling thiol group, maybe I should protect it with trityl to also avoid any reactivity.
I am going to try your suggestion

Offline rolnor

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Re: Synthesis of N-Acyl-N,O-alcohol
« Reply #20 on: January 10, 2020, 02:02:38 PM »
I would try the SEM-group for protection of the thiol, this group can be removed with fluoride (like TBAF) and you avoid acid. When you react the SEM-chloride with the thiolaldehyde you probably need only very mild base like pyridine since the thiol is such a strong nucleophile. With stronger base you get aldol with the aldehyde.

Offline Bertrand

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Re: Synthesis of N-Acyl-N,O-alcohol
« Reply #21 on: January 10, 2020, 04:25:28 PM »
hello!

you are right... to avoid any acid SEM-group is better than trityl

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