Butyl bromide → L-BUTHIONINE

L-buthionine-SR-sulfoximine is prepared as described in Griffith, O. W., The Journal of Biological Chemistry, Vol. 257, No. 22, pp. 13704-13712, 1982. Such preparation is as follows: L-methionine, obtained commercially, is reductively demethylated using sodium in liquid ammonia to produce L-homocysteine. The L-homocysteine is alkylated with 1-bromobutane to form L-buthionine. The L-buthionine is converted to L-buthionine-SR-sulfoximine by reaction with sodium azide in chloroform/sulfuric acid. The L-buthionine-SR-sulfoximine product is isolated by chromatography on Dowex 50(H+) resin. L-buthionine-SR-sulfoximine. 6 gms, containing approximately equal amounts of the two diastereomers was dissolved in 34 ml of hot water (boiling water bath) to a final concentration of 0.8M. The solution was allowed to cool; crystallization occurred spontaneously. After standing overnight at 4° C., the crystals were collected by filtration. The filtrate was evaporated to dryness under reduced pressure. The solid (4.1 gms) was suspended in 50 ml of absolute ethanol, and 5 ml of trifluoroacetic acid was added dropwise. Hexane, 50 ml, was slowly added over a period of about 10 minutes to the stirred, clear solution. Stirring was then stopped, and crystallization was allowed to occur at room temperature. After 2 hours, the crystals were collected by filtration, washed with hexane and ether, and dried under vacuum. The yield was 2.8 gms. The crystals, 2.8 gms, are added to 35 ml of ethanol with stirring to form a solution. To this solution is added with stirring 3.5 ml of trifluoroacetic acid, followed by 35 ml of hexane (added slowly over a 10 minute period). Then stirring is stopped and crystallization is allowed to occur at room temperature. After 2 hours the crystals are collected by filtration, washed with hexane and ether, and dried under vacuum. The yield is 1.6 gms. The crystals consist of L-buthionine-S-sulfoximine trifluoroacetic acid addition salt (of greater than 99% purity). The yield is about 50% based on the initial L-buthionine-S-sulfoximine content of the starting material. The acid addition salt is converted to pure free zwitterion by dissolving in water, 20 ml, applying the resulting solution to a column of Dowex 50 (H+), 1.5×20 cm, then washing with water to elute trifluoroacetic acid leaving L-buthionine-S-sulfoximine bound to the resin. The resin is washed with 1 liter of 3M ammonium hydroxide, and the eluent collected in 10 ml fractions. The fractions containing amino acid are pooled, evaporated to dryness at reduced pressure and traces of ammonia are removed by treating with water and evaporating.

ORD record

ord-e4a7b2b7c2e44ef1a19657e6e9a73f61

Source dataset

uspto-grants-1992_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05171885