Synthetic Approaches to N-Methylated L-Arginine, N
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- 作者：Dennis Schade ; Katrin Tö ; pker-Lehmann ; Jü ; rke Kotthaus ; Bernd Clement
- 刊名：Journal of Organic Chemistry
- 出版年：2008
- 出版时间：February 1, 2008
- 年：2008
- 卷：73
- 期：3
- 页码：1025 - 1030
- 全文大小：127K
- 年卷期：v.73,no.3(February 1, 2008)
- ISSN：1520-6904
文摘
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-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
ta.gif" BORDER=0 >-methylated analogues, a synthetic schemehad to be developed that would not lead to Nta.gif" BORDER=0 >-methyl-L-arginine only but also to its presumed metabolitesof NOS catalysis. Two basic synthetic approaches have been pursued to obtain Nta.gif" BORDER=0 >-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.