HMQCTOCSY
Introduction:
The standard experiments, HMQC, HMBC, COSY and TOCSY are
frequently not sufficient to solve complex structural problems. An impasse
arises because there is no easy way to distinguish the cabons that are 2, 3 and
4 bonds away from the correlated protons in an HMBC spectrum. This
problem occurs because the long range CH coupling constant
nJCH has no
simple relationship with the number of intervening bonds (n) between the
carbon and the proton. The best way of mapping the carbon backbone, 2D
INADEQUATE is usually impractical because a large amount of material
(>1OO mg) is required. INADEQUATE works because 1JCC
is much larger than nJCC,
and almost all magnetization is transfered between adjacent carbons.
There is an alternative technique that is practical for mapping that part of the
carbon backbone that is protonated. It is called HMQCTOCSY and combines
two very useful experiments. The HMQC part of the experiment correlates
protons with their directly bound carbons and the TOCSY part of the
experiment then relays the magnetisation around the proton spin system. The
extent of the relay is dependent on the length of mixing time in the TOCSY
experiment. Transfer between vicinal and geminal protons will almost always
occur before protons separated by 4 and 5 bonds and thus neighbouring CH
fragments can be unambiguously identified by properly tuning the mixing time.
The diagram below illustrates the information that can be gained from the
common types of inverse heteronuclear experiments.
The Problem:
Identify the C11-C11a and C15-C16-C16a fragments in the natural product,
drimentine D.
The Solution:
Each carbon resonance has crosspeaks at the resonance of the directly
bonded proton (negative crosspeak) and at the resonances of other
protons in the same spin system (positive crosspeaks). The spin
systems of C11-C11a and C15-C16-C61a are illustrated by lines
connecting the crosspeaks in the spectrum above. A mixing time was
chosen in this example to illustrate several relays through the
proton spin system. Notice that each spin system is broken by
quaternary carbons. HMBC is required to connect the adjacent
fragments mapped out by HMQCTOCSY.
Australian National University NMR Centre
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