Synthesis of syn and anti isomers of trans-cyclopropyl arginine.
There is currently considerable interest in arginine and its structural analogues in the context of nitric oxide synthase (NOS) substrates and inhibitors. Of particular interest are conformationally constrained arginine analogues used to probe the active sites of the three NOS isoforms. A simple procedure is described for the preparation of syn- and anti-trans-cyclopropyl arginine starting from the alpha-OBO-protected Cbz-dehydroglutamate. Cyclopropanation is effected by diazomethane addition followed by irradiation of the resulting pyrazoline and gives a 3:1 mixture of syn:anti isomers that can be separated by crystallization. Reduction of the ester to the alcohol followed by guanylation gives the fully protected cyclopropyl arginine analogues. The CBZ protecting groups are removed by hydrogenolysis and the OBO by mild acid treatment followed by base hydrolysis.
Fishlock
Dan
D
Department of Chemistry, University of Waterloo, Ontario, Canada. glajoie@uwo.ca
Guillemette
J Guy
JG
Lajoie
Gilles A
GA
D001120:Arginine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D002855:Chromatography, Thin Layer; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D019001:Nitric Oxide Synthase / Q000378:metabolism; D013237:Stereoisomerism
D004791:Enzyme Inhibitors; D001120:Arginine; D019001:Nitric Oxide Synthase