Facile synthesis of N-α-boc-1,2-dialkyl-l-histidines: Utility in the synthesis of thyrotropin-releasing hormone (trh) analogs and evaluation of the cns activity

A facile synthesis of N‐α‐Boc‐1,2‐dialkyl‐L‐histidines starting from N‐α‐trifluoroacetyl‐L‐histidine methyl ester is reported. The key steps involve direct and regiospecific N‐1(τ) ring‐alkylation of the N‐α‐trifluoroacetyl‐L‐histidine‐methyl ester by suitable alkyl iodide in the presence of NaH in...

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Published in:Journal of heterocyclic chemistry 2008-11, Vol.45 (6), p.1603-1608
Main Authors: Monga, Vikramdeep, Meena, Chhuttan Lal, Kaur, Navneet, Kumar, Satyendra, Pawar, Chandrashekhar, Sharma, Shyam Sunder, Jain, Rahul
Format: Article
Language:English
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Summary:A facile synthesis of N‐α‐Boc‐1,2‐dialkyl‐L‐histidines starting from N‐α‐trifluoroacetyl‐L‐histidine methyl ester is reported. The key steps involve direct and regiospecific N‐1(τ) ring‐alkylation of the N‐α‐trifluoroacetyl‐L‐histidine‐methyl ester by suitable alkyl iodide in the presence of NaH in DMF at −15 °C followed by homolytic free radical C‐2 alkylation via a silver catalyzed oxidative decarboxylation of alkylcarboxylic acid in the presence of ammonium persulfate under acidic conditions. The application of newly synthesized bioimidazoles was illustrated by their incorporation into thyrotropin‐releasing hormone (TRH). The synthesized TRH analogs were evaluated in vivo for analeptic activity. We report discovery of a TRH analog, which was found to potentiate the pentobarbital‐induced sleep in vivo.
ISSN:0022-152X
1943-5193
DOI:10.1002/jhet.5570450608