Solid-phase synthesis ninhydrin test

FIGURE 5.5 Schedule for the solid-phase synthesis of somatostatin, a 14-mer, on 10 g of resin reacted with 5 mequiv of the first amino acid, adapted from J. Rivier, J. Am. Chem. Soc. 96 2986, 1974. Min = time of mixing X2 = two times DCC = dicyclohexylcarbodiimide. Step 4 included 5% of (CH2SH)2 to prevent the oxidation of tryptophan. When the ninhydrin test on an aliquot after step 13 was negative, step 1 followed when positive, steps 9-13 were repeated. 

The monitoring of solid-phase synthesis in a real time quantitative manner has always been a goal since invention of the process. Many qualitative color tests exist, principal amongst these being the ninhydrin-based Kaiser test.f 1 The Kaiser test is less sensitive when the N-terminal is a secondary amine and for this reason many other tests have been applied.t °l Although a quantitative Kaiser test has been proposed,t l it has never achieved prominence as a routinely applicable method and the results are not usually available in time to influence progress of the reaction. 

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