Action of nitrogen trichloride on certain proteins II. Synthesis of methionine sulphoximine and other sulphoximines

Abstract

Methionine sulphoximine (I, R ═ CH 2 CH 2 CH(NH 2 )COOH, R' ═ CH 3 ) can be synthesized by the action of hydrazoic acid on methionine sulphoxide in the presence of concentrated sul-phuric acid as a catalyst and is shown to be identical with the toxic factor isolated from nitrogen trichloride-treated proteins. S-methylcysteine sulphoximine (I, R ═ -CH 2 CH(NH 2 )COOH, R' ═ CH 3 ) and dimethyl. sulphoximine (I, R , R' ═ CH 3 ) are prepared by a similar method from the corresponding sulphoxides; in rabbits, S-methylcysteine sulphoximine does not produce the toxic symp­toms obtained with methionine sulphoximine. Possible mechanisms are discussed for the reaction between hydrazoic acid and a sulphoxide.

Sulfoximine: Eine vernachlässigte Chance in der medizinischen Chemie

“…[7] Die Verbindung konnte anschließend durch die Umsetzung von Stickstoffwasserstoffsäure mit Methioninsulfoxid (1) in Gegenwart konzentrierter Schwefelsäure synthetisch hergestellt werden (Schema 1). [8] Die Sulfoximingruppe war bis dahin unbekannt gewesen. Natürlich war MSO (2) kein Naturstoff, da es chemisch aus peptidgebundenem Methionin in Weizen entstanden war.…”

“…synthetisch hergestellt werden (Schema 1). [8] Die Sulfoximingruppe war bis dahin unbekannt gewesen. Natürlich war MSO (2) kein Naturstoff, da es chemisch aus peptidgebundenem Methionin in Weizen entstanden war.…”

“…Synthese von Suloxifen(8). Reagentien und Bedingungen: a) 10, NaN 3 , PPA, 80 8C; alternativ: 11, KMnO 4 , Pyridin, RT; b) 2-Chlor-N,N-diethylethanamin, NaH, Toluol, Rückfluss.…”

Development of a Continuous Flow Sulfoxide Imidation Protocol Using Azide Sources under Superacidic Conditions

“…Research on the chemistry and properties of sulfoximines was triggered by the identification of methionine sulfoximine as the agent responsible for the toxicity of wheat flour treated with nitrogen trichloride (agene). , Nitrogen trichloride was used until the late 1940s for the bleaching of flour (agene process) when it was discovered that diets rich in agenized flour cause severe neurological disorders. Whitehead and Bentley accomplished the imidation of methionine sulfoxide with hydrazoic acid (HN 3 ) in the presence of concentrated sulfuric acid and demonstrated that the product is identical with the toxic factor isolated from agene-treated proteins . This was the first deliberate synthesis of a sulfoximine functionality and the interest in sulfoximine chemistry has increased steadily since then. − Sulfoximines contain an amphoteric nitrogen and, with two nonidentical carbon substituents on the sulfur atom, a configurationally stable asymmetric sulfur moiety.…”

“…However, subsequent deprotection to produce the synthetically attractive free sulfoximines can be difficult and is often accompanied by a significant loss of material . The reaction of sulfoxides with HN 3 , as demonstrated in the seminal work of Whitehead and Bentley in 1951, provides free sulfoximines directly and is clearly more atom economic (HN 3 method) . This reaction is usually performed with sodium azide and sulfuric acid in CHCl 3 as solvent. ,,− The method is exceedingly successful for the production of sulfoximines from sulfoxides if both carbon substituents are either methyl or aryl.…”