Steroids, stereospecific oxidation

The structure and decomposition of the peroxomolybdenum-olefin complex have been investigated. Further kinetic studies suggest the structure of the transition complex shown in Eq. 29. The double bond is attacked by a positively charged oxygen.labeling has demonstrated that the oxo oxygen is not affected in the reaction. A -Steroids are oxidized with surprising stereospecificity this is evidence in favor of the 1,3-dipolar mechanism. ... 

A facile method for the stereospecific labeling of carbon atoms adjacent to an oxygenated position is the reductive opening of oxides. The stereospecificity of this reaction is due to virtually exclusive diaxial opening of steroidal oxides when treated with lithium aluminum hydride or deuteride. The resulting /ra/w-diaxial labeled alcohols are of high stereochemical and isotopic purity, with the latter property depending almost solely on the quality of the metal deuteride used. (For the preparation of m-labeled alcohols, see section V-D.)... 

Lithium aluminum deuteride reduction of the 2a,3a-oxide function has been carried out with a number of different 5a-steroids (227). ° The isotopic purity of the resulting 2 -d,-3a-ols (228) is usually 96-100%. By mild oxidation, under Jones conditions, these alcohols can be converted into stereospecifically labeled monodeuterio ketones (229) ° of high isotopic purity. (For an alternate preparation of certain a-monodeuterio ketones, see section VI-B.)... 

This enantiomeric specificity has been of interest in other contexts, and stereospecific biotransformation has been observed. Examples include the enantiomeric oxidation of sulfides to sulfoxides (Chapter 11, Part 2) and steroid and triterpene hydroxylation (Chapter 7, Part 2). 

Hydrogenolysis of epoxides to alcohols by catalytic hydrogenation over platinum requires acid catalysis. 1-Methylcyclohexene oxide was reduced to a mixture of cis- and /ranj-2-methylcyclohexanol [652]. Steroidal epoxides usually gave axial alcohols stereospecifically 4,5-epoxycoprostan-3a-ol afforded cholestan-3a,4/J-diol [652 ]. 

The oxidations accomplished by microorganisms or enzymes excel in regiospecificity, stereospecificity, and enantioselectivity. Although the yields of such oxidations are sometimes fair and even low, optical purity (enantiomeric excess) is usually very high and frequently 100%. The spectrum of microbial and enzymatic oxidations is unbelievably broad many different positions in steroidal rings can be hydroxylated by different microorganisms, and usually, only one diastereomer is formed. From achiral molecules, optically active compounds are generated. 

Microbiological conversions, microbiological iranrformaiions conversions of materials occurring in one or more stages, and catalysed by microorganisms. M.c. are the result of microbiological enzyme action, and often have no importance for the microbial cell. Several M.c. are important in the pharmaceutical industry. Examples are the stereospecific conversions of steroids, oxidation of sorbitol to sorbose by Acetobacter suboxydans (in the production of vitamin C), and the addition of acetaldehyde to benzalde-hyde by Saccharomyces cerevisiae. The product of this last reaction is phenylacetylcarbinol, a precursor for D-ephedrine synthesis. 

Kallner (66) studied the stereospecific formation of 5a steroids by the reduction of 3-keto- -derivatives with Li in liquid ammonia (Fig. 7). Oppenauer oxidation of methyl cholate provided the 3-dehydro derivative IX which was hydrolyzed to the free acid (X) and the product dehydrogenated with Se02 to the dihydroxy-3-ketochol-4-enoic acid (XI). The unsaturated acid (XI) was reduced with Li in liquid ammonia, and the product methylated to provide a mixture from which XII was separated from the desired ketone... 

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