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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
Author(s) -
Monga Vikramdeep,
Meena Chhuttan Lal,
Kaur Navneet,
Kumar Satyendra,
Pawar Chandrashekhar,
Sharma Shyam Sunder,
Jain Rahul
Publication year - 2008
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570450608
Subject(s) - chemistry , alkylation , decarboxylation , histidine , methyl iodide , oxidative decarboxylation , lymantria dispar , imidazole , thyrotropin releasing hormone , stereochemistry , in vivo , nucleophile , phenacyl , analeptic , medicinal chemistry , organic chemistry , catalysis , amino acid , hormone , biochemistry , biology , neuroscience , ecology , lepidoptera genitalia , microbiology and biotechnology
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.