Reduction of Insulin with Tributylphosphine

Treatment of bovine insulin with 3 mole of tributylphosphine in the presence of excess ethylene imine in aqueous 1‐propanol at pH 8.2 leads to complete reduction and aminoethylation, affording the aminoethylated insulin A and B chains in excellent yield. Reduction with 1 mole of tributylphosphine under the same conditions is attended by disulphide exchange: The product is a mixture of partially reduced and aminoethylated species which, on further reduction and carboxymethylation, afford A‐ and B‐chain derivatives with varying ratios of S‐aminoethyl‐ and S‐carboxymethyl substituents.