The dithiasuccinoyl (Dts)-protecting group for ammo acids is removed by thiols (2 equivalents) through the intermediacy of an open-chain carbamoyl disulfide. Starting materials, intermediates, and products can be separated from one another on the standard amino acid analyzer 0.9 x 56cm column of sulfonated polystyrene resin with 0.2 N sodium citrate buffers. Compounds are detected with the standard ninhydrin-hydrindantin reagent because the hydrindantin acts as a reducing agent and the released amino acid reacts in situ with the ninhydrin to give a purple color. Elution times, integration constants, and the ratios of absorbances at 570 and 440 nm are tabulated. Quantitative conversion of dithiasuccinoyl amino acids to the parent amino acids can be achieved with 0.1 N sodium hydroxide, 0.01 M alcoholic sodium borohydride, 0.1 M triphenylphosphine or 2 mM tri-n-butylphosphine in dioxane-H,O (9:l) or water, and with a variety of thiols under various conditions. The chromatographic methodology is applicable to the determination of rate constants of the pseudo-first-order reductive deprotection of dithiasuccinoyl amino acids.
Recently, we described the synthesis (l-3) of several dithiasuccinoyl (Dts)2-amino acids 1 and proposed the use of these compounds as amino-protected derivatives for orthogonal (3) schemes of peptide synthesis. Cleavage of the disulfide bond of 1 with a thiol generates an open-chain carbamoyl disulfide intermediate 2, which reacts further to give the free amino acid 3 (Scheme I). Two equivalents of the thiol 4 are oxidized to the disulfide 5, and the net reaction is driven to completion by loss of two equivalents of gaseous carbonyl sulfide. Reducing agents other than thiols are also effective for the deprotection of Dts-amino acids.
In order to establish the validity of Scheme I, and to follow the course of the reaction, it was necessary to have a rapid, convenient, and quantitative analytical method to measure the starting materials, intermediates, and products. The present paper presents t This paper is dedicated to the memory of Dr.