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Synthesizing octopine from arginine and 2-bromopropionic acid
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Limbia Sakarias
Synthesizing octopine from arginine and 2-bromopropionic acid
Arginine methyl ester with a nitro group on the guaninidine is commercially available. A reductive amination with the commercially available methyl pyruvate (ethanol or methanol with sodium cyanoborohydride or sodium triacetoxyborohydride at room temperature) will give you the dimethyl ester of nitrooctopine. This should be a good reaction and it is easy to purify by chromatography at this point. Mild basic hydrolysis of the esters followed by hydrogenation over Pd/C to remove the nitro group will give octopine.
edit: As noted by @user55119 this will give a mixture of diastereomers.
Arginine methyl ester with a nitro group on the guaninidine is commercially available. A reductive amination with the commercially available methyl pyruvate (ethanol or methanol with sodium cyanoborohydride or sodium triacetoxyborohydride at room temperature) will give you the dimethyl ester of nitrooctopine. This should be a good reaction and it is easy to purify by chromatography at this point. Mild basic hydrolysis of the esters followed by hydrogenation over Pd/C to remove the nitro group will give octopine.
edit: As noted by @user55119 this will give a mixture of diastereomers.
@user55119 Hydrogenation of the nitro to deprotect the guanidine of arginine is the first method mentioned in Greene's "Protection Groups in Organic Synthesis", see J. Org. Chem. vol 44 (1979) 3442. You are correct about the possible diasteromers,More
The reductive amination is likely to give diastereomers, one of which is the undesired epimer of the dimethyl ester of nitrooctopine. This could be a serious problem if the More
1) One of the C=O's is in the ester group, its presence activates the ketone C=O to attack by the -NH2 2) The reductive amination can be done on pyruvic acid but the conditions are more complex - this is an easy reaction with the esters. 3) The hydrogenation cleaves the N-N bond (see the ref. in my comment above). 4) The presence of the nitro group withdraws electron density from the whole guanidine group making it less nucleophilic.More
I have several questions: (1) There are 2 C=O's on (methyl)pyruvate; is there a reason to expect only one of them to react? (2) What is the purpose of the esters? Solubility in the solvents used for the reaction, maybe? (3) Wouldn't the hydrogenation of the nitro group give an aminoguanidine instead of regenerating the desired guanidine? (4) Wouldn't the secondary amine is the guanidine (the guanidine nitrogen closest to the carboxyl) also react and create secondary products?More
Arginine methyl ester with a nitro group on the guaninidine is commercially available. A reductive amination with the commercially available methyl pyruvate (ethanol or methanol with sodium cyanoborohydride or sodium triacetoxyborohydride at room temperature) will give you the dimethyl ester of nitrooctopine. This should be a good reaction and it is easy to purify by chromatography at this point. Mild basic hydrolysis of the esters followed by hydrogenation over Pd/C to remove the nitro group will give octopine.
edit: As noted by @user55119 this will give a mixture of diastereomers.
Arginine methyl ester with a nitro group on the guaninidine is commercially available. A reductive amination with the commercially available methyl pyruvate (ethanol or methanol with sodium cyanoborohydride or sodium triacetoxyborohydride at room temperature) will give you the dimethyl ester of nitrooctopine. This should be a good reaction and it is easy to purify by chromatography at this point. Mild basic hydrolysis of the esters followed by hydrogenation over Pd/C to remove the nitro group will give octopine.
edit: As noted by @user55119 this will give a mixture of diastereomers.
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