Differentially-protected steroidal triamines; scaffolds with potential for medicinal, supramolecular, and combinatorial chemistry.
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 > or 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 approximately 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.
del Amo
Vicente
V
School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK.
Siracusa
Laura
L
Markidis
Theodoros
T
Baragaña
Beatriz
B
Bhattarai
Khadga M
KM
Galobardes
Marta
M
Naredo
Gregorio
G
Pérez-Payán
M Nieves
MN
Davis
Anthony P
AP
D000596:Amino Acids / Q000737:chemistry; D001386:Azides / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods*; D019826:Cholic Acid / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D015394:Molecular Structure; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D000596:Amino Acids; D001386:Azides; D011073:Polyamines; D019826:Cholic Acid