Differentially-protected steroidal triamines; scaffolds with potential for medicinal, supramolecular, and combinatorial chemistry

Abstract
Cholic acid 2a has been converted into two new orthogonally-protected triamino scaffolds, 13 and 14. The synthesis proceeds via the bis-Boc-NH-substituted azide 10, for which an improved preparation is described. After removal of the Boc groups, the two axial amines are differentiated through a novel monoprotection employing 1-(2-nitrobenzenesulfonyloxy)-benzotriazole 29. Regioselectivity of ≥50 : 1 is achieved, presumably reflecting an exceptional sensitivity to steric hindrance. Protection of the remaining amino group as Boc or Alloc gives the scaffolds in 40% overall yield from cholic acid. Scaffold 13 has been sequentially deprotected and derivatised with N-carbamoyl amino acids, to give a model for tripodal peptide libraries.

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