Dear friends,
For my original question, I got a lot of responses so fast. Rather than
replying each one, I write to appreciate all the ideas and suggestions.
First of all, I did run temperature from 3C-50C, almost no change in
chemical shift for the methlene protons, so that rules out the
possiblity of different rotomers of amide or exchange at the chiral -SO-
location. Second, I did have authentic -SO2- compound, which has
different chemical shift with either of the isomers and we have MS and
elemental analysis for the structures, so it is not due to different
oxidation impurities. Third, we have run the NOESY, in one isomer, the
two methylene protons (3.0 and 3.5ppm) have similiar NOEs to both the
methyl (1.6ppm) and the ortho-aromatic protons; in the other isomer, the
proton at 3.2ppm has stronger NOE to the ortho aromatic proton, but much
weaker NOE to the methyl (1.8ppm) proton; the proton at 3.4ppm is just
the opposite. Clearly the conformations are very different in these
isomers, not like what I show in the model which one expect similar
NOEs. It is tempting to use these, but due to the flexibility of the
single bond rotation, many conformations can possibly satisfy these, and
I can not draw a confident conclusion. Last, we do have a chiral center
at the -C(OH)(CH3)- position, so there are two chiral centers in the
isomers.
Based on the response, I don't think I can assign them by NMR only. Joe
from NCI suggest to use CD to define the optical isomers, based on
Koji's methods. Shame on me, since I took Nakanishi's class and still
remembered vividly about his gesture using his arms showing "+,-" of the
relative orientations of chromophores, and yet I did not think about
using it on this compound !! At this point, I think what I really need
is an X-ray structure and we will go on with it. Once we have the X-ray
structures, it may be interesting to see how the -SO- affect the NMRs.
As always, thank everyone to share their expertise with us on this
problem and you have a great day.
Best regards,
Wei Li, Ph.D.
Assistant Professor
Department of Pharmaceutical Sciences
University of Tennessee Health Science Center
847 Monroe Ave., Room 327A
Memphis, TN 38163
Tel 901-448-7532
Fax 901-448-6828
----- Original Message -----
> From: Wei Li
> To: ammrl_at_chemnmr.colorado.edu
> Cc: wli_at_utmem.edu
> Sent: Wednesday, March 17, 2004 5:54 PM
> Subject: can anyone help with the isomer assignment?
Dear friends,
I know this may not be very suitable for this email list, but we would
greatly appreciate if anyone can give any suggestions as which isomer is
which based on the spectra. If it is not possible, what other
experiments would be helpful to define the structures, or what
literature is good for us to look. The spectra and related information
is posted via the following link:
http://cop.utmem.edu/pharmacy/pharmsci/faculty/med_chem/wLi/here_is_my_puzzle.htm
Thank you.
Wei Li, Ph.D.
Assistant Professor
Department of Pharmaceutical Sciences
University of Tennessee Health Science Center
847 Monroe Ave., Room 327A
Memphis, TN 38163
Tel 901-448-7532
Fax 901-448-6828
Received on Thu Mar 18 2004 - 16:28:38 MST