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

Abstract

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).

1,1-Dioxonaphtho[1,2-b]thiophene-2-methyloxycarbonyl (α-Nsmoc) and 3,3-Dioxonaphtho[2,1-b]thiophene-2-methyloxycarbonyl (β-Nsmoc) Amino-Protecting Groups

“…The solvent was removed with a rotary evaporator to give a residue which prior to purification was shown by 1 H NMR analysis to contain 1.46% of the DL-diastereomer. A sample for elemental analysis was prepared by recrystallization from DCM/hexane to give 302 mg 1 H NMR spectrum for the DL-diastereomer (which would be the same as that for the LD-diastereomer) the same method was used as described above except that DL-H-Ala-OMe.HCl was substituted for the L-isomer. This gave a roughly 50-50 mixture of the LL-and LD-diastereomers (m.p 80°C) for which the OMe singlets were found at δ 3.63 and 3.70, respectively.…”

Microwave Assisted Alcoholysis of Isocyanates Derived from Nα-[(9-fluorenylmethyl)oxy]carbonyl Amino Acids: Synthesis of N-Fmoc-N1-Z-/Boc-/Alloc-/Bsmoc-gem-diamines

“…Both preparation as well as the isocyanates derived from N a -Fmoc-a-amino acids as coupling agents for the synthesis of peptidyl ureas was demonstrated to be completely free from racemization (Patil and Sureshbabu, 2003). This paper demonstrates the synthesis of N-Fmoc-N 1 -urethane (Z-/Boc-/Alloc-/Bsmoc) (Carpino et al, 1997(Carpino et al, , 1999 protected gem-diamines and their utility in the synthesis of retro-inverso peptides.…”

Synthesis of 1,1-Dioxobenzo[b]thiophene-2-ylmethyloxycarbonyl (Bsmoc) Protected N-Methyl Amino Acids by Reduction of Bsmoc-5-Oxazolidinones and Their Use in Peptide Synthesis

“…Bsmoc group [18] , introduced by Louis Carpino, for amino protection has significant advantages over the Fmoc group. The key difference of this invention is the mode of cleavage mechanism through Michael-like attack of base on , unsaturated sulfones [19] followed by elimination of CO 2 and amino component (Scheme 1).…”