Non-stereoselective Formation of 3.ALPHA.,7.ALPHA.,12.ALPHA.,24-Tetrahydroxy-5.BETA.-cholestan- 26-oic Acid during Cholic Acid Biosynthesis.

Abstract

Incubation of (25RS)-, (25R)- and (25S)-3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestan-26-oic acid (THCA, 6, 6a, 6b) and (24E)-3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-en-26-oic acid (7) with rat liver mitochondria gave all four stereoisomers (9a,9b,9c,9d) of 3 alpha,7 alpha,12 alpha,24-Tetrahydroxy-5 beta-cholestan-26-oic acid (TeHCA). The corresponding 27-nor analogs (10,11) were also converted non-stereoselectively to a 1:1 mixture of the epimeric 24-hydroxy compounds (12).

Recombinant 2-enoyl-CoA hydratase derived from rat peroxisomal multifunctional enzyme 2: role of the hydratase reaction in bile acid synthesis

“…The oxidative cleavage of THCA, an intermediate in the biosynthetic pathway of cholic acid, is believed to proceed by a mechanism similar to the peroxisomal β-oxidation of fatty acids [6]. The first intermediate of this reaction sequence, ∆#%-THCA-CoA, has the (E)-configuration under physiological conditions [9,16,24,25]. In rat liver peroxisomes, this reaction is now known to be catalysed exclusively by a THCA-CoA oxidase distinct from fatty acyl-CoA oxidase and pristanoyl-CoA oxidase [7,[26][27][28].…”

“…In rat liver peroxisomes, this reaction is now known to be catalysed exclusively by a THCA-CoA oxidase distinct from fatty acyl-CoA oxidase and pristanoyl-CoA oxidase [7,[26][27][28]. Using a rat liver mitochondrial fraction, some authors have shown that all four diastereomers of 24-OH-THCA are formed from (25R,S)-THCA [25] and that all four 24-OH-THCA diastereomers can be metabolized to cholic acid [10], whereas others have shown the exclusive formation of (24R,25S)-24-OH-THCA orevised assignment, (24R,25R) [11]q in both rat liver homogenates [12] and purified peroxisomes [24].…”

The biosynthesis of steroids and triterpenoids

“…Both (25S)-and (25R)-THCAs were utilised by crude peroxisome preparations 992 and all four possible 24,25-diastereoisomeric products of the intermediate 3 ,7 ,12 ,24-tetrahydroxy-5 -cholestanoyl-CoA (TeHCA; 72) -identified by comparison with synthetic tetrols 993 (pentols are also available) 994 -could be detected using either (25R)-or (25S)-THCA as substrates with mitochondrial preparations. 995 However, in peroxisome preparations, both (25R)-and (25S)-THCA were converted only to 24R,25S-TeHCA via the intermediate (24E)-3 ,7 ,12 -trihydroxy-5 -cholest-24-enoyl-CoA ( 24 -THCA; 71). 996 It may be possible to reconcile these somewhat conflicting results with the expectation that enzymes involved in the -oxidation pathway should be stereospecific by noting the outcome of experiments with purified enzyme preparations.…”

Controlled Expansion of a Molecular Cavity in a Steroid Host Compound

“…General Methods. Bishomocholic acid ( 2 ) was prepared by the previously reported method . All chemicals and solvents were commercially available and used without any purification.…”

“…Bishomocholic acid (2) was prepared by the previously reported method. 22 All chemicals and solvents were commercially available and used without any purification. Infrared spectra were recorded on a JASCO IR-Report-100 or JASCO IR-810 spectrometer.…”