277. Syntheses of poly-S-alkyl-L-cysteines

Abstract

Various S-alkylcysteine derivatives have been prepared and polymerisedProperties of the by various methods through their N-carboxy-anhydrides. amino-acids and their polymers are reported. SOME S-alkylcysteine derivatives have been found to occur in Nature. isolated S-allyl-L-cysteine S-oxide ( a h ) from garlic. S-Methylcysteine S-oxide has been found in various plants; the deoxo-compound was enzymically synthesised from serine and methanethiol and has been suggested as an intermediate in the microbial biosynthesis of c y~t e i n e .~ S-Ethylcysteine has antituberculosis a~t i v i t y .~ S-Dichlorovinylcysteine produces fatal aplastic anzmia in young calve^.^ In an investigation of the biological mode of action of alkyl alkanesulphonates as alkylating agents,6 S-alkyl derivatives of cysteine were isolated. Finally poly-S-benzyl-7 and -S-allyl-cysteine have been synthesised.It seemed interesting. to synthesise a series of S-alkylcysteines and their polypeptide polymers. General methods for the preparation of S-alkylcysteines, summarised by Armstrong and Lewis,g comprise Schotten-Baumann reaction of an alkyl halide with cysteine in liquid ammonia or in sodium hydroxide solution. In the latter procedure the reactants are dissolved in alcohol-water, and sufficient sodium hydroxide is added to neutralise the hydrogen halide formed and to enable salt formation with the carboxyl group of cysteine. We have found that on use of a smaller quantity of alkali, sufficient to remove only the hydrogen halide acid formed, the reaction proceeds relatively fast and the S-alkylcysteine is precipitated, as it is formed, provided it is insoluble in the alcohol-water mixture used; thus the equilibrium shifts in favour of the formation of additional alkylcysteine. In this way it was possible to prepare pure crystalline S-ethyl-or S-benzyl-cysteine in high yield in a comparatively short time. The use of a smaller amount of alkali is especially advisable in the preparation of S-alkylcysteine derivatives which are soluble in water and insoluble in ethanol, and thus are difficult to free from sodium halides. For the same reason triethylamine instead of sodium hydroxide is recommended.The following S-alkyl-L-cysteines were prepared and polymerised : the known methyl, ethyl, propyl, isopropyl, butyl, and pentyl derivatives as well as the new hexyl-, dodecyl-, and l-naphthylmethyl-L-cysteine.Reaction of the reactive a-chloromethylnaphthalene and of benzyl chloride with cysteine was complete within a few to 30 min., while the reaction with dodecyl bromide required several days.Generally, the lower S-alkylcysteines, such as methyl, ethyl, and allyl, are soluble in water and insoluble in ethanol. The higher homologues are less soluble in water and more soluble in ethanol. Recrystallisation of the former is effected from aqueous ethanol, and of the latter from a large volume of water, ethanol, or dilute acetic acid. Ascending paper chromatography with (A) 80% aqueous phenol, (B) butanol-acetic acid-water (40 : 10 : 10) (C) 65% aqueous pyridine, o...

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