5- Diazo-4-oxo-L-norvaline

Azaserine, 5-diazo-4-oxo-L-norvaline (DONV) and 6-diazo-5-ketonorleucine (DON) are other examples of mechanism-based irreversible inhibitors51). They are stable to nucleophilic attack, but on enzymatic protonation, they are converted to the reactive diazonium ions (30). N-Nitroso compounds have been proposed as irreversible inhibitors of proteolytic enzymes. N-Nitrosolactam (31) can inhibit chymotrypsin... 

The prototypical inhibitors in this series are azaserine, 5-diazo-4-oxo-L-norvaline (DONV), and 6-diazo-5-ketonorleucine (DON). All these inhibitors contain the diazo group as their active moiety. 

Diazo-4-oxo-L-norvaline (DONV), 35, 36, 415, 432-435 synthesis of, 433, 434 Diazosulfanilic acid, 64 a-Diazothiol esters, 73 Diazotization, 94, 98 Diazotrifluoropropionate, 73... 

DON, see 6-Diazo-5-oxo-norleucine DONV, see 5-Diazo-4-oxo-L-norvaline Drugs, see aho specific substances binding to receptor, 574 opiate, see Opiate receptors Dye-ligand conjugate, 563 Dyes, 00... 

The white crystalline diazoketone is dissolved in 10 ml of dry chloroform. Hydrogen chloride gas is bubbled slowly for 2 min into the solution that is cooled in ice. A spectrum of the product, 5-chloro-4-oxo-A -benzoxycarbonyl L-[5- C]norvaline-a-benzyl ester, should exhibit no diazo absorption. The chloroform is removed by flash evaporation and the residual material is suspended in 20 ml of 6 Af HCl and heated at 70° for 10 hr. The supernatant solution is decanted and replaced with 20 ml of 6 iV HCl, and the procedure is repeated until no insoluble material remains. The solutions are combined, and the products generated by removal of the protecting groups (benzyl alcohol, toluene) are removed by lyophilization the remaining colorless, moist powder may be dried under reduced pressure over PaO.-,. The net yield of L-2-amino-4-oxo-5-chloropentanoic acid hydrochloride is about 80% (49 mg, 0.24 mmole specific activity 1.16 Ci/mole). The chloroketone hydrochloride can be recrystallized from acetone-water to give the free base m.p. 151°-152° (dec.). 

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