Abstract:
Two enzyme mechanisms were investigated: the
21-dehydroxylation of corticosteroids by Eubacterium lentum
and the dehalogenation of 4-chlorobenzoic acid by Pseudomonas
sp. CBS 3.
,
Chemical and enzymic methods of reduction of 21-oxo
steroids were used to generate C-21-d1 compounds of
tetrahydrodeoxycorticosterone, with both predominant
stereochemistries. It was found that during the dehydroxylation
the pro-S hydrogen at the C-21 position was lost preferentially.
This suggests that the enzyme removes the pro-S hydrogen during
binding to the active site as the ene-diol.
To study the hydrolytic replacement of chlorine by
hydroxyl , p-chlorobenzoic acid-d4 was prepared and sent to
Germany for an ~ncubation with an enzyme preparation of
4-Chlorobenzo~te Dehalogenase. Results suggests the possible
loss of deuterium during the conversion of p-chlorobenzoate to
p-hydroxybenzoate, from all four ring positions. Many methods
of preparing the control compound p-hydroxybenzoic acid-d4 were
investigated.
