MIESCHER Degradation

Additional applications are exemplified by the well-known Meystre-Miescher degradation of the bile acid side chain and, more recently, in the preparation of a-pyrones from a,iS-unsaturated lactones. ... 

A variation of this procedure, the Meystre-Miescher-Wettstein Degradation (Miescher Degradation) removes three carbons from the chain ... 

MIESCHER DEGRADATION. Adaptation of the Barbier-Wieland carboxylic acid degradation to pcrmil simultaneous elimination of three carbon atoms, as in degradation of the bile acid side chain to the methyl ketone stage. Conversion of the methyl ester of the bile acid to the tertiary alcohol, followed by dehydration, bromination. dehydrohalogenatinn, and oxidation of the diene yields die required degraded ketone. 

A further advance of major importance in the practical utilization of the bile acids for cortisone syntheses was the replacement of the laborious Barbier-Wieland degradation (cf. Fig. 2) by the Meystre-Miescher degradation. As applied by Wettstein and Meystre (1947) to methyl 3a-acetoxy-ll-ketocholanate (VI, R = Ac R = CH3), this procedure involves reaction with phenylmagnesium bromide and acetylation to produce the diphenyl olefin (IX), which upon bromination with N-bromo-suooinimide and dehydrobromination smoothly yields the diene (X). 

Although the specific oxidation of X to pregnan-3a-ol-ll,20-dione acetate (XI) does not appear to have been described in the literature, this step is carried out in precisely the same manner as described for the corresponding 12-broinide (Fig. 5) from which XI is equally accessible. Alternatively, it is possible to carry out the Meystre-Miescher degradation (Hershberg et al., 1952a) with 3a,12/3-dihydroxy-ll-ketocholanic acid (III) and to treat the resulting diphenyl olefin (VII) with phosphorus tribromide. The 12-bromodiphenyl olefin (VIII) can then be transformed further to XI, as indicated in Fig. 5 (X — XIV). 

Other references related to the Miescher degradation are cited in the literature. ... 

Michael Reaction Michaelis-Arbuzov Reaction Miescher Degradation Mignonac Reaction Milas Hvdroxvlation of Olefins Miller (see Doebner-Miller Reaction)... 

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