Cysteine as a sustainable sulfur reagent for the protecting-group-free synthesis of sulfur-containing amino acids: biomimetic synthesis of l-ergothioneine in waterElectronic supplementary information (ESI) available: Complete reaction schemes for the previously described synthesis of 2-thiohistidine and l-ergothioneine using phenylchlorothionoformate (S1) and KSCN (S2) as sulfur source, Figures of the 1H NMR-analysis of the reaction mixture (S3) and copies of spectral data (1H NMR and 13C NMR) f

Biomass-derived cysteine was used as a sustainable sulfur source for the synthesis of rare sulfur-containing amino acids, such as l -ergothioneine ( 4 ), which might be a new vitamin, and various l - or d -2-thiohistidine compounds. Key in this simple, one-pot two-step procedure in water is a bromine-induced regioselective introduction of cysteine followed by a novel thermal cleavage reaction in the presence of thiols, a safer alternative to hazardous red phosphorus. Besides avoiding hazardous sulfur reagents, the new protecting-group-free approach reduces drastically the total number of steps, compared to described procedures. The main drawback, i.e. handling of liquid bromine as an activating and oxidizing reagent in water, was addressed by evaluating four alternative methods using in situ generation of bromine or HOBr, and first encouraging results are described. Natural and novel sulfur-containing amino acids are prepared in the l - and d -form via a new regioselective one-pot two-step procedure.