Synthesis and spectroscopic characterisation lithocholic acid derivatives

Abstract

The synthesis of five lithocholic acid derivatives, 5β-cholane-3α,24-diol (2), 3α-hydroxy-5β-cholan-24-yl tosylate (3), 5β-cholan-3α,24-yl ditosylate (4), 3α-tosyloxy-5β-cholan-24-yl chloride (5) and 3-oxo-5β-cholan-24-al (6) have been described.

Synthesis of hydroxy acids of dinorcholane and 5β-cholane

“…2 3-Oxo-23,24-dinorchol-4-en-22-al (1), pyridinium chlorochromate (PCC) and trimethylsilyl cyanide (TMSCN) were purchased from Aldrich and used as received. The reactions were monitored and the purity of the products was assessed by thin-layer chromatography (TLC) performed on silica gel (Merck type 60) and visualized under UV illumination and/or by I 2 vapor.…”

“…However, if a chiral centre already exists next to the carbonyl carbon, two possible diastereomeric products are formed, and they are not of equal amounts. As part of our on-going studies on the synthesis and reactions of steroid monomers and dimers, [2][3][4][5][6][7][8] we now report on the development of a convenient and general method for the synthesis of diasteriomerc (55:45) dinorcholane hydroxy acids and 5β-cholane hydroxy acid using readily available dinorcholanal and 5β-cholane-3α,24-diol as the starting materials.…”

Synthesis of Pregnenolone and Methyl Lithocholate Oxalate Derivatives

“…The fact that small changes in the functionalities attached to the steroid skeleton can cause marked changes in their biological activity has prompted synthetic chemists to carry out structural modifications of steroids [1,2]. As part of our on-going studies on the synthesis of various steroidal derivatives [3][4][5][6][7][8], we report on the synthesis of five new pregnenolone and methyl lithocholate oxalate derivatives that contain an oxalate ester linkage at C-3 of the steroid molecules.…”

“…In its 13 C NMR spectrum, the signals for a desheilded oxymethine (δ 77.1), an oxymethylene (δ 63.1) and a methyl (δ 14.0), respectively, for C-3, -OCH 2 CH 3 and -OCH 2 CH 3 and two carbonyl carbons for the oxalate moiety at δ 157. Oxalic acid mono (pregn-5-en-20-one)-3β-yl ester (3) was synthesized from pregnenolone (1) using 4 molar equivalents of (COCl) 2 in DCM, and H 2 O was added in the work-up step (Scheme 1). HRFABMS analysis revealed the [M+NH 4 ] + ion at m/z 406.2589, which confirmed the molecular formula C 23 H 32 O 5 for 3.…”

Synthesis of 3α-chlorinated Methyl Lithocholate Derivatives

“…Methyl lithocholate (1), a bile acid derivative, is a structurally well-known compound containing a rigid steroid part as well as a flexible side chain with an ester functional group at the end of the chain and can easily be modified to its derivatives. As part of our on-going studies on the synthesis of various new C-24 steroidal derivatives, 1,2 we now report on the convenient synthesis and spectroscopic analyses of four new 3a-chlorinated methyl lithocholate derivatives, 3a-chloro-5bcholan-24-oic acid methyl ester (2), 3a-chloro-5b-cholan-24ol ( 3), 3a-chloro-5b-cholan-24-yl tosylate ( 4) and ethyl (3achloro-5b-cholan)-24-yl oxalate (5).…”