Subject: Energetics of Walden inversions

From: "Hr Dr. S. Shapiro" <[email-masked]>
Date: Thu, 6 Oct 1994 17:11:04 +0100 (MET)

Dear Colleagues;

     Recently I had a dicussion with an associate regarding the stereo-
chemistry of enzymic hydroxylations at position C-14 of steroidal molecules.
Most such substrates have a 14-alpha-H configuration, whereas many products
have a 14-beta-OH configuration.  The question arose as to whether this
could be due to a simple Walden inversion.  I opined that whilst a simple
Walden inversion, in which the departing hydrogen leaves on the alpha-side
opposite to the trajectory of the incoming hydroxyl group, might sound rea-
sonable, upon reflection it might not be such a feasible mechanism because
in such a rigid polycyclic structure as a steroid the tertiary carbon atom
C-14 occupies a keystone position and that it might be energetically too
unfavourable for such a Walden inversion to occur at C-14, at least not
without affecting more distal positions in the molecule.  It later occurred
to me that perhaps the C-14 position might also be too sterically hindered
for a Walden inversion to readily occur there.

     With that introduction, my questions are:

     (1) does anyone have hay definitive information or references re the
         the mechanism of enzymic hydroxylation of steroidal substrates at
         C-14 (or tertiary carbons in other rigid polycyclic molecules)
         with net inversion of configuration?

     (2) would anyone care to comment on the arguments I put forth against
         hydroxylation proceeding by a simple Walden inversion at C-14 of
         steroidal-type molecules?

     (3) can the unsubstituted C-14 position (with an alpha-H atom) be re-
         garded as a hindered position?

     (4) does anyone have any information on the energetics of Walden inver-
         sions at primary vs. secondary vs. tertiary carbon atoms?  If so,
         could you please share your information with me, and send me rele-
         vant references?

     I thank all responders in advance for their generous cooperation in the
above matter.

Yours sincerely,

(Dr.) S. Shapiro
Institut fuer orale Mikrobiologie und allgemeine Immunologie
Zentrum fuer Zahn-, Mund-, und Kieferheilkunde der Universitaet Zuerich
Plattenstrasse 11
Postfach
CH-8028 Zuerich, Switzerland

Internet: [email-masked]
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