Abstract:
Fungal metabolism of halogenated and related steroids was
investigated. The fungi Aspergillus niger ATCC 9142, Curvularia lunata
NRRL 2380 and Rhizopus stolonifer ATCC6227b were studied in this regard.
2l-Fluoro-, 2l-chloro, 2l-bromo- and 2l-methyl-pregn-4-ene-3,20diones
were prepared and incubated with ~ niger (a C-2l-hydroxylator)
in order to observe the effect of the C-2l substituent on the metabolism
of these substrates. In all four cases, the C-2l substituent prevented
any significant metabolism of these substrates.
llB-Fluoropregn-4-ene-3,20-dione was prepared and incubated with
C. lunata (an llB-hydroxylator) and ~ stolonifer (an lla-hydroxylator).
With ~ lunata, the ll-fluoro- substituent prevent hydroxylation at
the 11 position, but diverted it to a site remote from the fluorine atom.
In contrast, with ~ stolonifer the llB-fluoro- substituent, although
slowing the apparent rate of hydroxylation, did not prevent its occurrence
at the 11a- position.
llB-Hydroxypregn-4-ene-3,20-dione was also incubated with R.
stolonifer. The llB-hydroxy-;group did not appear to have any significant
effect on hydroxylation at the lla- position.
The incubation of a substrate, unsaturated at a favoured site of
hydroxylation with Rhizopus arrhizus ATCC 11145 provided a complex mixture
of products; among them were both the a and S epoxides. The formation
of these products is rationalized as arising because of the lack of
regio- and stereospecificity of the hydroxylase enzyme(s) involved.
