The "triamino-analogue" of methyl allocholate; a rigid, functionalised scaffold for supramolecular chemistry.

Cholic acid has been converted into triamine with the all-trans polycyclic allocholanoyl skeleton and co-directed, axial amino groups; the potential of this system as a scaffold is illustrated by conversion to a preorganised anion receptor.

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.

A New Generation of "Cholaphanes": Steroid-Derived Macrocyclic Hosts with Enhanced Solubility and Controlled Flexibility.

The macrocyclic "cholaphanes" 3a-c were synthesized from the inexpensive steroid cholic acid. Like earlier relatives they feature substantial cavities with inward-directed hydroxyl groups, suitable for binding polar molecules such as carbohydrates in nonpolar media. New features are the externally directed alkyl chains, promoting solubility in organic solvents, and (in the case of 3b/c) reduced conformational freedom resulting from truncation of the steroidal side-chain. In particular, modeling shows that the smallest macrocycle 3c possesses very little flexibility, preferring an open conformation which is also revealed in the X-ray crystal structure of its pentahydrate. NMR studies indicated that all three cholaphanes form 1:1 complexes with octyl beta-D-glucoside in CDCl(3), with K(a) = 600-1560 M(-)(1). Cholaphanes 3b/c proved able to extract methyl beta-D-glucoside from aqueous solutions into CHCl(3). The transport of methyl beta-D-glucoside across a chloroform barrier was also demonstrated for 3c.