The 1,1-Dioxobenzo[b]thiophene-2-ylmethyloxycarbonyl (Bsmoc) † Amino-Protecting Group

• Published in: Journal of organic chemistry 1999-06, Vol.64 (12), p.4324-4338
• Main Authors: Carpino, Louis A, Ismail, Mohamed, Truran, George A, Mansour, E. M. E, Iguchi, Shin, Ionescu, Dumitru, El-Faham, Ayman, Riemer, Christoph, Warrass, Ralf
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo982140l

Full details are presented for use of the Bsmoc amino-protecting group for both solid phase and rapid continuous solution syntheses. Application to the latter methodology represents a significant improvement over the corresponding Fmoc-based method for rapid solution synthesis due to the opportunity to use water or saturated sodium chloride solution rather than an acidic phosphate buffer to remove all byproducts, with consequent cleaner phase separation and higher yields of the growing peptide. Comparison of the Bsmoc and Bspoc functions showed that the former, because of steric hindrance, does 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 shown for the Fmoc analogues. Applications of Bsmoc chemistry to peptide sequences incorporating the base sensitive Asp-Gly unit gave less contamination due to aminosuccinimide formation than comparable syntheses involving standard 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 the use of insoluble piperazino silica as well as the polyamine TAEA which simplified aqueous separation of the growing, but nonisolated peptide product, from excess acylating agent and other side products formed in the deblocking process. By the appropriate choice of base, one can act selectively at either site of a molecule which incorporates both β-elimination and Michael acceptor sites as protective units (Bsmoc vs Fm and Fmoc vs Bsm).