A -hydroxy L-arginine

Figure 16. Proposed L-arginine-assisted NOS oxygen activation. First, substrate L-arginine (only guanidinium shown) donates a proton to the per-oxo-iron, facilitating 0-0 band cleavage and conversion to a proposed oxo-ferryl 7r-cation radical species. The radical species then rapidly hydrox-ylates the neutral guanidinium to A "-hydroxy-L-arginine. (Adapted from Ref. [100].)...

The anisyl group was used since the phenyl oxaziridines simply isomerized to nitrones upon acid treatment. The yields were modest (30-40%), but the products were optically pure. A similar method was used to make 5-A -hydroxy-L-arginine and 6-A -hydroxy-L-ornithine, and the optically active hydroxylamine precursor of dopastin. ... 

A 2006 report detailed the three-step synthesis of N-hydroxy guanidines from N-Cbz protected thioureas for the synthesis of A/ -hydroxy-L-arginine (060L4035). 

L-arginine A/G-hydroxy-L-arginine L-citrulline nitric oxide... 

The synthesis of /Vc -hydroxy-l.-arginine was published by Pufahl and Marietta82. This compound was shown to be a substrate for the production of nitrite and nitrate, for the production of NO and for the synthesis of citrulline. When 15N-NHA was used as substrate, the NO2 /NO3 produced were found to contain undiluted 15iV. Therefore, they concluded that the iVG-hydroxy-L-arginine is a true substrate in NO synthesis. 

Using a spectrophotometric method, McMillan and Masters93 obtained evidence that bNOS contained a heme group that reacted with L-arginine and with iVG-hydroxy-L-arginine (an intermediate) and /VG-rncthyl-i.-arginine (an inhibitor). They therefore concluded that the heme was an oxygen donor. 

A variety of L-arginine-based inhibitors was tested by Komori and coworkers114. They found AG-methoxy-L-arginine as well as AG-hydroxy-L-arginine and L-arginine itself to oxidize NADPH. The mechanism of the effects remain to be determined. 

Wallace, G. C., Gulati, P., and Fukuto, J. M. (1991). N -Hydroxy-L-arginine A novel arginine analog capable of causing vasorelaxation in bovine intrapulmonary artery. Biochem. Biophys. Res. Commun. 176, 528-534. 

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