Richard P. Bonar-Law

Cyclocholates : synthesis and ion binding

Abstract Cyclic polyesters of cholic acid, ‘cyclocholates’, with two to six steroid units in the ring have been prepared and their ion-binding ability demonstrated.

Cholic acid as an architectural component in biomimetic/molecular recognition chemistry; synthesis of the first “cholaphanes”.

Abstract The readily available steroid cholic acid (1) has several advantages as a precursor for extended, preorganised molecular frameworks. In the present work, full details are given for the conversion of 1 into “cholaphanes” 2a,b, the first macrocyclic steroid derivatives intended for use in molecular recognition chemistry. Diacetoxyketone 11 was prepared from methyl cholate 8 and treated with an arylmanganese reagent to give, after elimination of water and steroselective hydrogenation, monomer unit 13. 2a was obtained by cyclodimerisation (up to 40% overall yield from 8), and 2b by subsequent deacetylation.

Self-associating cyclocholates

Abstract Self-complementary steroidal triamides have been prepared and their reversible self-assembly into molecular cylinders demonstrated.

The benzostabase protecting group for primary amines : application to aromatic amines

The “benzostabase” (BSB) protecting group has been applied to primary aliphatic amines. It can be introduced via a dehydrogenative silylation employing an air- and moisture-stable reagent, and is appreciably more acid-stable than the related “stabase” group. BSB protection has been used in a stereoselective synthesis of amino-alcohols involving the addition of organometallic reagents to protected amino-aldehydes under “non-chelation control”.

Morphine recognition by a porphyrin–cyclocholate molecular bowl

A molecular bowl has been prepared by constructing a metalloporphyrin on one face of a tetrameric cyclocholate; the bowl selectively binds morphine by a combination of nitrogen–metal ligation and hydrogen bonding.

Cholic acid as an architectural component in biomimetic/ molecular recognition chemistry; NMR and molecular mechanics study of a “tetra-acetoxycholaphane”.

Abstract A detailed NMR analysis of cholaphane 2 has resulted in the measurement of most of the 1 H and 13 C chemical shifts, and many of the 1 H- 1 H coupling constants. Some of this information has been used to provide “NMR constrains” for a molecular mechanics study of the macrocycle, resulting in a set of four minima which are proposed to dominate the conformational equilibrium of 2 in CDCl 3 .

New procedures for selectively protected cholic acid derivatives. Regioselective protection of the 12α-OH group, and t-butyl esterification of the carboxyl group

Effective procedures have been developed for the preparation of various selectively protected cholic acid derivatives. Treatment of cholic acid or methyl cholate with trifluoroacetic anhydride in THF, followed by partial deacylation under acidic conditions, leads to the 12α-trifluoroacetates (10a) and (10m), respectively. Trifluoroacetic anhydride may also be used as a condensing agent in the synthesis of t-butyl cholates. Particularly notable is the preparation of the ester (10b), which incorporates both these developments and is arguably the most efficient method yet for differentiating between positions 7 and 12 in the cholic acid nucleus.

Concise synthesis of a porphyrin–cyclocholate molecular bowl

An efficient sequence is described from cholic acid to a porphyrin–cyclocholate molecular bowl.

Diastereo- and enantio-selective binding of octyl glucosides by an artificial receptor

1 n H NMR titration experiments have been used to measure the association constants between tetrahydroxycholaphane 1a and the octyl glucosides 2-5; the cholaphane has been shown to discriminate quite effectively between the stereoisomers, showing a diastereoselectivity of ca. 5.5:1 in respect of 2 and 3, and an enantioselectivity of ca. 3:1 in respect of 3 and 5.

Synthesis of steroidal cyclodimers from cholic acid; a molecular framework with potential for recognition and catalysis

Macrocycles (2a–f) were synthesized from cholic acid (1a) in up to 33% overall yield; the “cholaphane” framework on which they are based has substantial potential variability and should prove useful in biomimetic chemistry.