Novel steroidal dimers: 3a,3'a-dihydroxy-5b-cholan-24-oic acid piperazine diamide 3, its 3a,3'a-bis(trifluoroacetoxy) protected derivative 2, and 3a,3'a-bis(pyridine-n-carboxy, n = 2-4) derivatives 4-6 and their Ag + -complexes have been prepared. A novel cholaphane 7 has also been synthesized from 3 by cyclization with terephthalic acid by Yamaguchi method. Products were characterized by 13 C and 15 N NMR chemical shifts and MALDI-TOF MS. In addition, MO-calculations (PM3) for 3 and 7 were performed.The design of novel molecular architectures is one of the most exciting fields in the supramolecular chemistry. 1 Macrocyclic and cleft type supramolecular structures are especially interesting because they could bind substrates on their cavity or trap around a substrate molecule, respectively. Bile acids are very appropriate compounds from the molecular engineering point of view. Their chiral, rigid framework and chemically different hydroxyl groups make them attractive building blocks in tailoring supramolecular hosts. 2-8 Bile acid based macrocycles consists of two to four bile acid units joined together by various spacer groups, called cholaphanes. A cholaphane, reported previously by us, 9 consists of two lithocholic acid moieties, an ethylene glycol joint, and terephthalic acid spacer. Pandey and Singh have synthesized a cholic acid based cholaphane including an ethylenediamine bridge and a terephthalate spacer group. 10 One example of the bile acid based cleft type structures is a host molecule which Kohmoto et al. have synthesized from 3a-aminocholanoate derivative and naphthalene-1,4,5,8-tetracarboxylic acid dianhydride. 11 We have also prepared some molecular clefts 12,13 and investigated their Ag + -cation binding properties. 13 In this study we have chosen piperazine as a bridging group for our lithocholic acid derivatives because piperazine has metal complexing capabilities and it is a good hydrogen-bond acceptor, which makes its derivatives interesting for supramolecular complexation chemistry. 14 In addition, Zhang et al. have demonstrated 15 that some N,N'-disubstituted piperazine compounds are high-affinity ligands for s-1 and s-2 type receptors, which have potential functional role in several important physiological and biochemical processes.The entire synthetic route leading to 3a,3'a-bis(pyridinen-carboxy)lithocholic acid piperazine diamides 4-6 (n = 2-4) and cholaphane 7 is described in the Scheme.3a-Trifluoroacetoxy-5b-cholan-24-oyl chloride (1) was synthesized from lithocholic acid (3a-hydroxy-5b-cholan-24-oic acid), whose 3a-hydroxy was first protected with trifluoroacetic acid anhydride leading to 3a-trifluoroacetoxy-5b-cholan-24-oic acid. The latter was then refluxed with thionyl chloride giving 1 in ~ 100% yield. Detailed synthetic description, 13 C NMR, MS, and elemental analysis data of 3a-trifluoroacetoxy-5b-cholan-24-oic acid and 1 has been described before. 9 Our first aim was to synthesize a piperazine monoamide from 1 using starting compounds in a molar ratio 1:1. However, NMR and MA...

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1 H, 13 C and 15 N NMR and electrospray ionization time-of-flight mass spectrometric characterizations of five lithocholate esters of piperazine diamides are described. Two of them are cholaphane-type cyclic structures esterified with 2,2 -bipyridine-4,4 -and pyridine-2,6-dicarboxylic acid and the other three esters are open structures comprising two or four lithocholyl residues. The conformational preferences of the dimeric congeners were examined by using molecular modelling and variable-temperature 1 H NMR techniques.

Novel 2,2'-bipyridine-4,4'-dicarboxylates 3a-3d of four bile acid methyl esters have been synthesized from 2,2'-bipyridine-4,4'-dicarboxylic acid 1 and the corresponding bile acid methyl esters (methyl lithocholate 2a, methyl chenodeoxycholate 2b, methyl deoxycholate 2c, and methyl cholate 2d). In addition to the desired products, 3α -(2,6-dichlorophenylcarboxy) bile acid methyl esters 4a-4d were obtained. The structures of 3a-4d have been ascertained by 1 D 1 H and 13 C NMR, 2 D PFG 1 H, 13 C HMQC, and MALDI TOF MS. Molecular weights and 13 C NMR chemical shifts of 3a-4d have been presented. The geometry of 3a has been optimized semiempirically at the PM3 level and it has been observed that the minimum energy structure of 3a is a open type conformation due to lack of attractive intramolecular electrostatic interactions between the heads of the molecule which would have favoured the formation of cleft type structure. The synthesized bipyridine-bile acid conjugates are interesting structures from the molecular recognition point of view because they could have potential to form complexes with some transition metal ions, for example with silver, cadmium, and ruthenium.