SYNTHESIS OF ⳑ-CYSTINE (3,3'-Dithiodialanine)

• Place 500g of washed, dried human hair(1) in a 3-litre round-bottomed flask and add 1 litre of a 1:1 mixture of concentrated hydrochloric acid and formic acid. 

• Fit a reflux condenser and boil the mixture gently under reflux (fume cupboard) until the biuret test is negative (about 20 hours). 

• Treat the hydrolysate with about 12g of acid-washed decolourising charcoal, filter hot and concentrate the filtrate to a thick syrup under reduced pressure using a rotary evaporator. 

• Dissolve the residue in 250 ml of water and add with shaking warm 50 per cent aqueous sodium acetate until the solution is no longer acid to Congo red. 

• Leave the mixture at room temperature for 3 days, and then filter off the precipitate of crude cystine and wash it with 50 ml of warm water. 

• Dissolve the product in 750 ml of 1m hydrochloric acid, treat the hot solution with 5g of acid-washed decolourising charcoal and filter. 

• If the filtrate is more than faintly yellow, repeat the treatment with a further 5g of charcoal. 

• Neutralise the filtrate to Congo red and with sodium acetate solution as previously and leave at room temperature for 5-6 hours (2). 

• Filter off the colourless plates of purified ⳑ-cystine, wash with two 50 ml portions of hot water, then with ethanol and finally with ether. The yield is about 25g (5%); m.p. 260-262 °C (decomp.); [𝜶]ᴅ²⁰, -216° (c 0.69 in 1ᴍ HCl).

Notes to keep in mind:

1. Raw material can usually be obtained from barbers' shops. The washing procedure must remove effectively grease and natural oils. A warm aqueous solution of a good quality detergent is satisfactory; it is important that the washing medium should not be alkaline as this may markedly reduce the yield of cystine. Raw sheep's wool, adequately cleaned, may also be used as the starting material if available, but processed material (e.g. old woollen garments, etc.) may give poor yields.

2. The crude product contains some of the aromatic amino acid tyrosine which is present in the original hydrolysate. A portion of this is removed by the charcoal treatment and by the hot-water washing, but the final recrystallised cystine may be contaminated with tyrosine if the suggested 5-6 hour period for crystallisation is greatly exceeded.