Structure Elucidation - Natural Products Chemistry: Sources, Separations, and Structures - page 23

3 Structure Elucidation
Elucidation of chemical structures requires piecing together a combination of chemi-
cal and spectroscopic information. Typically, the spectroscopic tools most frequently
used are nuclear magnetic resonance (NMR), which includes 1 H- and 13 C- NMR;
ultraviolet (UV); infrared (IR); and mass spectrometry (MS). Use of circular dichro-
ism (CD) and X-ray crystallography are often used in support of determining the
stereochemistry and the absolute configuration. Early studies on the structural eluci-
dation of a natural product required large amounts of material, preferably recrystal-
lized to homogeneity. The need for a sharp melting point and elemental analysis were
paramount. This information was followed by a combination of degradation studies
and derivatization reactions, and eventually chemical synthesis to confirm the struc-
ture. With the advent of modern-day spectroscopic techniques, microgram amounts
are often sufficient to complete the determination of structure using only spectro-
scopic techniques.
3.1 NUCLEAR MAGNETIC RESONANCE
Only nuclei with spin number I ≠ 0 can absorb/emit electromagnetic radiation. If
a nucleus has an even mass A and even charge Z, then the nuclear spin I is zero.
Examples are 12 C, 16 O, and 32 S. However, a nucleus with a mass I = n/2, where n
is an odd integer, for example, 1 H, 13 C, 15 N, and 31 P, in which case it is possible to
detect their nuclear magnetic resonance (NMR) signals. The chemical shift of the
nucleus is the difference between its resonance frequency and a standard. Usually,
this quantity is reported in parts per million (ppm) and given the symbol delta, δ. In
NMR spectroscopy as illustrated in Figure 3.1 for the simple compound ethanol, this
standard is often tetramethylsilane, Si(CH 3 ) 4 , abbreviated as TMS. In the ethanol
HISTORICAL NOTE
In the 20th century, as improvements continued in separation techniques and
more compounds were isolated from plant and microbial sources, there were
quantum leaps in the spectroscopic techniques used to determine chemical
structures. An anecdotal story made the rounds in the United Kingdom in
the early 1960s, when a Nobel Laureate, sitting on the panel of a candidate's
Ph.D. thesis defense, challenged the student to show he had determined that
his isolated chemical compound was pure. All the spectral techniques were
described in detail to support the purity and to determine the chemical struc-
ture. Alas, the candidate was told to come back and redefend his thesis when
he had taken the melting point.
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