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

Abstract

Syntheses of bile acid cyclooligomers with 12‐ and 7,12‐oxo groups (6a−d, 7a−c, 8a−b) by the Yamaguchi method are described. Cyclotrimerization is the principal reaction route for these cholic acid systems. Conversion of 7‐ and 12‐hydroxy groups in cholic acid (1a−b) to oxo groups (4a−c, 5a−c), followed by macrocyclization (6a−d, 7a−c, 8a−b) and selective reduction of the oxo groups back to hydroxy ones without cleaving the 24‐carboxylic ester linkages (11) constitutes a new strategy in the synthesis of cyclocholates having unprotected hydroxy groups.

Bile acid toxicity structure–activity relationships: Correlations between cell viability and lipophilicity in a panel of new and known bile acids using an oesophageal cell line (HET-1A)

“…Introduction of 3a-azides (15, 26) (i.e., with retention of configuration) was accomplished by generating first the b-bromides (39,42). The b-azides (16,27) could be obtained by direct SN2 substitution on the a-mesylates (40,43). Similarly, the 7-b azido analog of UDCA (34) was generated by treating the appropriately protected CDCA-derived mesylate (45) with NaN 3 in DMPU followed by deprotection in aqueous base.…”

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.…”

“…Total assignations of the 13 C-NMR spectra of steroids have been done over 20 years and a great number of the 13 C-NMR shift data of bile acids and their derivatives have been published [ 58 , 59 , 60 , 61 , 62 , 143 , 144 , 145 , 146 , 147 , 148 , 149 ]. Dias et al .…”

Synthesis and comparative spectroscopic analysis of two chenodeoxycholic acid (CDCA) derivatives with closely related 7α-ester moieties

“…The route for synthesizing methyl 3a-(ethoxycarbonyloxy)-7a-(allyloxy)-5b-cholanoate (8) of 7a-OH on 7a-monohydroxyl ester 3 with TMCS and imidazole in THF, 12 followed by dried TBAF desilylation of 6 to presumably produce an alkoxide intermediate, which undergoes S N 2 with allyl bromide to afford allyl ether. 13 The results of mass spectroscopy further informed us that the molecular weight of this compound (562.3492) is 44 mass units higher than that of anticipated product (8) with MW (518.36). The 44 mass units difference is consistent with CO 2 insert between alkoxide ion and allyl group.…”