The 1,1-dioxobenzo[b]thiophene-2-ylmethyloxycarbonyl (Bsmoc) amino-protecting group

Full details are presented for use of the Bsmoc amino-protecting group for both solid phase and rapid continuous solution syntheses. Application to th e latter methodology represents a significant improvement over the correspo nding Fmoc-based method for rapid solution synthesis due to the opportunity to use water or saturated sodium-chloride solution rather than an acidic p hosphate buffer to remove all byproducts, with consequent cleaner phase sep aration and higher yields of the growing peptide. Comparison of the Bsmoc a nd Bspoc functions showed that the former, because of steric hindrance, doe s not suffer from the competitive or premature deblocking observed with the Bspoc system. Because of its incorporation of a styrene chromophore, resin loading of Bsmoc amino acids could be followed as has previously been show n for the Fmoc analogues. Applications of Bsmoc chemistry to peptide sequen ces incorporating the base sensitive Asp-Gly unit gave less contamination d ue to aminosuccinimide formation than comparable syntheses involving standa rd Fmoc chemistry because a weaker or less concentrated base could be used in the deblocking step. Experimental details are presented for building up peptides in solution via the continuous methodology. Deblockings involved t he use of insoluble piperazino silica as well as the polyamine TAEA which s implified aqueous separation of the growing, but nonisolated peptide produc t, from excess acylating agent and other side products formed in the debloc king process. By the appropriate choice of base, one can act selectively at either site of a molecule which incorporates both beta-elimination and Mic hael acceptor sites as protective units (Bsmoc vs Fm and Fmoc vs Bsm).