jo702150dn00001>journals/joceah/73/i03/figures/jo702150dn00001.gif" ALIGN="left" HSPACE=5> |
N-Methylated arginines such as asymmetric dimethyl-
L-arginine (ADMA) and monomethyl-
L-arginine(NMMA) are known as potent physiological inhibitors of nitric oxide synthases (NOSs). To explore apossible physiological and pharmaceutical relevance of
N-methylated analogues, a synthetic schemehad to be developed that would not lead to
N-methyl-
L-arginine only but also to its presumed metabolitesof NOS catalysis. Two basic synthetic approaches have been pursued to obtain
N-methylated derivativesof
L-ornithine,
L-citrulline,
L-arginine, and
N-hydroxy-
L-arginine. A first attempt utilized conventionallyprotected
L-ornithine, i.e., the
tert-butyl ester and Boc-amine, and led to three end compounds in excellentyields. Simultaneous protection of the
-amino acid moiety by formation of boroxazolidinones, particularlyby employing 9-borabicyclo[3.3.1]nonane (9-BBN-H), proved to be a convenient option to perform sidechain modifications and led to all of the desired end compounds. Additionally, enantiomeric excess (ee,%) of crucial synthetic intermediates and end compounds was determined by chiral HPLC.