Supramolecular Adducts of Ferrocene and Five Bile Acid Derived Triolides

Abstract

Formation of supramolecular adducts of ferrocene (guest) and cyclic head-to-tail trimers (hosts) derived from bile acid: 3a-hydroxy-5~-cholan-24-oic acid triolide ( l ) , 3a-hydroxy-7-oxo-5P-cholan-24-oic acid triolide (2), 3a-hydroxy-12-oxo-SPcholan-24-oic acid triolide (3), 3a-hydroxy-?a-trifluoroacetoxy-6P-cholan-24-oic acid triolide (4) and 3a-hydroxy-12a-TFA-5P-cholan-24-oic acid triolide (5) (TFA = trifluoroacetoxy) have been studied by 'H NMR. The best computer-assisted data fitting on the 'H-NMR chemical shift data was given by a 1:2 (guest/host) association model. The association constants vary in the range 170-990 M-', 7-0x0-substituted triolide 2 and 12a-TFA triolide 5 showing the largest and smallest values respectively. Generally, triolides bearing substituents at the position C-7 (2 and 4), when compared with the 12-substituted derivatives 3 and 5, seem to favour adduct formation, while a TFA group at the position C-7 or C-12 seems to hinder the adduct formation in comparison with the 0x0-substituted congeneers. This finding may be accounted for by the bulky character of the TFA group when compared to the 0x0 group.Cholaphanes and cyclocholates are cholic acid (3a,7a, 12a-trihydroxy-5~-cholan-24-oic acid) based macrolides capable of binding other biologically interesting molecules [']. Cholic acid macrolides have been mentioned as a structural fragment of a molecular bowl capable of selective binding of morphineL2]. Generally, bile acids have a rigid steroidal skeleton with curved profile which facilitates the design of macrolide frameworks"1. Furthermore, bile acids are of low cost, easily available, and occur in nature as pure enantiomers. These properties are of great importance in, for example, the design of asymmetric synthesis and catalysis as aided by these macrocyclic hosts.In our previous paper, we reported a 'H-NMR investigation into the interaction of anisole with five different bile acid based macrolides [3]. The unsubstituted macrolides (from cyclic lithocholate diolide to pentolide) did not show any tendency to recognize anisole. Cyclolithocholates can, therefore, serve as suitable reference structures in the study of other bile acid derived macrolide~ [~]. As a continuation of our previous study, we now wish to report a 'H-NMR investigation into the interaction of ferrocene (dicyclopentadienyliron) with five bile acid triolides: 3a-hydroxy-5P-cholan-24-oic acid triolide (l), 3u-hydroxy-7-oxo-5~-choIan-24-oic acid triolide (2), 3a-hydroxy-12-0x0-5P-cholan-24-oic acid triolide (3), 3a-hydroxy-7a-TFA-5P-cholan-24-oic acid triolide (4) and 3a-hydroxy-12a-TFA-5P-cholan-24-oic acid triolide (5).Ferrocene is selected as a guest molecule for several reasons: (i) it is a typical metallocene, having a 3-D molecular structure, (ii) ferrocene derivatives have been used as templating agents in the synthesis of bipyridium-based cyclophanesL4], and (iii) ferrocene itself has been frequently used as a guest molecule in a 1 : 1 second-sphere adduct with tetracationic cycl~phane [~] and in many cyclod...

Bile Acids as Building Blocks of Supramolecular Hosts

“…Cyclocholates are macrocyclic polyesters (macrolactones) with two to six steroid units formed by head-to-tail cyclization of the bile acids. The most general procedure for the synthesis of these cyclic oligomers has been to prepare them from monomeric or linear dimeric derivatives of bile acids by modified Yamaguchi macrolactonization [ 52 ] using DCBC (2,6-dichlorobenzoyl chloride) and DMAP (4- N , N -dimethylaminopyridine) as coupling reagents ( Scheme 1 ) [ 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ]. Gao and Dias have reported [ 62 ] the macrolactonization of lithocholic acid using DCC (dicyclohexylcarbodiimide) instead of DCBC in cyclization process.…”

“…Lappalainen et al . have studied molecular recognition properties of cyclic cholanoates by the 1 H NMR titration method using anisole [ 53 ] and ferrocene [ 55 ] as guest. The 7α- and 12α-trifluoroacetoxy substituted cholanoate triolides showed clear molecular recognition properties towards anisole and the formation of 1:2 adducts between ferrocene and cyclic triolides were also observed.…”

Macrocyclic bile acids: from molecular recognition to degradable biomaterial building blocks

“…Finally, ferrocene was found to form 1 : 2 guest-host complexes with bile acid-based triolides, with moderately high binding constants. 96 Another important topic in supramolecular chemistry is that of anion complexation. To this aim, a convenient method for stabilising anions consists of decorating a rigid structure with hydrogen donating functionalities capable of interacting with a central anion.…”

Cyclocholates with 12-Oxo and 7,12-Oxo Groups

“…Except for minor variation in 13 C-NMR assignments, the NMR spectra of 7b agree with previously published ones. [24] …”