Silvia Poli

Biotransformations on steroid nucleus of bile acids

The bile acids in mammals are all derivatives of 5 beta-cholan-26-oic acid. They represent the major quantitative pathway by which cholesterol is metabolized in the body. This article covers the microbial and enzymatic transformations of free, saturated bile acids, that kept unaltered the C-24 cyclopentane-perhydrophenantrene nucleus. The bile acids that have been considered include the primary cholic and chenodeoxycholic acids, the secondary deoxycholic and lithocholic acids as well as the relevant dehydrocholic, ursocholic and ursodeoxycholic acids. Among the bile acid biotransformations, attention is paid to reactions that lead to pharmaceutically significant compounds. This is the case of 7 alpha-hydroxy epimerization of chenodeoxycholic acid to ursodeoxycholic acid, currently used for cholesterol galistone dissolution therapy and in the treatment of cholestatic liver diseases. Emphasis has placed on reporting reactions that may be of general interest and on the practical aspects of work in the field of biotransformations.

Kinetic resolution of vic-diols by Bacillus stearothermophilus diacetyl reductase

Abstract The kinetic resolution of several racemic syn- and anti-1,2-diols by enzymatic oxidation with Bacillus stearothermophilus diacetyl reductase is described. The enantiomerically pure (R,R)- and (R,S)-diols are recovered in almost quantitative yield.

Microbial oxidation with Bacillus stearothermophilus : high enantioselective resolution of 1-heteroaryl and 1-aryl alcohols

Abstract The enantioselective resolution of the racemic 1-heteroaryl- and 1-arylethanols 1a-h via microbial oxidation with Bacillus stearothermophilus to give the R -enantiomers with high enantiomeric excesses is described. The kinetic resolution of 1-(2-thienyl)ethanol 1b by oxidation with Acinetobacter calcoaceticus anitrat to S -enantiomer (ee 100%) is also reported.

REGIOSELECTIVE MICROBIAL OXIDATION OF BILE ACIDS

Abstract High regioselectivity in the microbial oxidation of C 7 , C 3 and C 12 hydroxyl groups of cholic, chenodeoxycholic, deoxycholic and hyocholic acids 1–4 is reported. The tested microrganisms have been isolated from 50 enviromental samples withdrawed from an industry that extracts and purify bile acids.

Kinetic resolution of 1-aryl- and 1-heteroaryl ethanols by oxidation with Baker's yeast

Abstract The kinetic resolution of racemic 1-aryl and 1-heteroaryl ethanols 1a-e via oxidation by Bakers yeast to give the R-enantiomer is reported.

Enantioselectivity in microbial reduction of prochiral carbonyl groups: A wide screening toward R and S isomers

Abstract More than fifty yeast and mould strains were tested in the reduction of 2-acylthiazoles 1–5. The possibility of obtaining R or S enantiomers with high enantioselectivities from various species and strains is described.

Regiospecific oxidoreductions catalyzed by a new Pseudomonas paucimobilis hydroxysteroid dehydrogenase

Abstract The preparative-scale regio- and stereo-specific oxidation of hydroxy groups and reduction of keto functions at C(3) of several C 21 bile acids, catalyzed by a new 3α-hydroxysteroid dehydrogenase (3α-HSDH), is reported. The crude enzyme, isolated from the cells of Pseudomonas paucimobilis , revealed the presence of a further enzymatic fraction containing a secondary alcohol dehydrogenase (SADH), that has been used to recycle the cofactor.

Oxidation with Bacillus stearothermophilus in heptane

Abstract The first example of oxidation with bacteria in heptane is reported. The kinetic resolution of endo-bicyclic octen- and heptenols is obtained. The methodology is simpler and the volume of the reactions is smaller than in water.

Microbial approach to chiral 2-thiazolyl γ- and δ-lactones

Abstract The synthesis of chiral 2-thiazolyl γ- and δ-lactones6 and7 via microbial reduction of the appropiate keto esters to the homochiral hydroxy esters followed by chemical lactonization is described. Some attempts of enzymatic lactonization of the racemic hydroxy esters or resolution of racemic lactones are also reported.