When dissolved in DMSO, the spectra of the benzyl derivative is similar to that of bis-CBZ-ß-alethine in every way except for the methylene peak presumed to be adjacent to sulfur.
The benzyl derivative produces a different spectra in water than it
does in DMSO which may be consistent with different solvating mechanisms
protic and aprotic solvents, respectively.
The proton spectra of vitaletheine V4 is unique compared with other
spectra in this family of compounds. Although, the couplings and relative
intensities of the protons on the nitrogen (far-downfield triplets) and
on the methylenes adjacent to the nitrogen (quartets around 3 ppm) are
very similar to those for the CBZ starting material and the benzyl derivative,
there is no evidence for the benzyl moiety at about 5 and 7.4 ppm. This
indicates that the carboxyl moiety is still attached to the terminal amine,
and makes a strong case for the carbamate tautomer in DMSO solution; the
carbonimidate tautomer may be more abundant in aqueous solution, but its
dominating presence in DMSO would have resulted in the observation of triplets
instead of quartets for the methylenes coupled to the nitrogen moieties.
V4 is easily decarboxylated and there is some evidence that DMSO facilitates
this reaction, possibly by helping to remove zinc ions from the more stable
As expected from theoretical calculations of chemical shifts, the decarboxylation
of vitaletheine V4 has an almost imperceptible effect upon the shifts
of its methylenes. Similarly, phosgenations
to vitalethine and reductions of ß-alethine to ß-aletheine
in the presence of zinc ions do not cause dramatic changes in proton NMR
spectra. Unfortunately, these reasonably small changes in NMR spectra upon
reduction and carboxylation (phosgenation) lead many to suspect that their
attempts to phosgenate ß-alethine to
have failed, and in some instances this is clearly the case due to departures
from the established protocols.
These examples help to illustrate the limits of using NMR for making structural assignments for these compounds since phosgenation and decarboxylation cause shifts in proton and carbon spectra that are so subtle that they can be missed altogether. Because of this, other forms of analyses always should be performed on each preparation containing carbamates or carbonimidates.
In stark contrast to these results, reduction of the benzyl derivative under certain mild conditions causes some striking changes consistent with a rearrangement to a vitaletheine V4-like compound.
||WWW Links||Outline||e-mail us|