Full Paper
The 1H and 13C NMR spectroscopic data for sclerophytin F
were compared to those of sclerophytin A, the triol 44 and the
two other diastereomeric triols prepared by Paquette and co-
workers that possess an R configuration at C-3.[4e,f] The NMR
spectroscopic data for the four triols did not match those re-
ported for sclerophytin F.
Table 4. Comparison of 13C NMR spectroscopic chemical shifts (in CDCl3)
for sclerophytins 3–7, the structures of which have been secured by total
synthesis or X-ray analysis.
Position
3[a]
4[a]
5[b,c]
6[c–e]
45.3
F[f]
7[f]
1
45.2
90.5
74.8
39.9
29.4
79.9
77.0
45.4
78.2
52.6
147.9
31.6
24.9
43.7
29.1
16.0
22.0
30.3
23.1
109.1
45.5
90.5
74.8
39.8
28.1
85.0
75.9
45.5
78.0
53.2
147.9
31.9
24.8
43.6
29.0
16.1
21.9
30.2
23.7
109.2
171.8
21.5
44.6
90.5
74.9
41.0
30.0
90.5
76.1
45.1
78.1
53.0
147.9
31.6
25.9
43.7
29.0
15.9
22.0
29.4
23.9
109.1
57.0
45.4
91.9
86.6
35.9
30.5
80.1
77.0
45.8
78.2
52.9
147.6
31.4
24.7
43.9
29.1
15.7
21.9
23.2
22.3
109.3
45.0
91.4
86.2
34.5
29.5
77.0
79.6
79.5
81.1
52.5
148.6
31.6
24.8
43.7
29.0
16.2
21.9
23.0
17.7
109.9
169.5
22.7
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
91.1
74.4
40.9
27.2
88.4
76.1
45.1
78.6
53.8
148.4
31.9
25.2
44.0
29.3
15.7
22.1
29.9
24.8
109.2
64.8
15.3
At this stage, six of the eight diastereomeric triols with vary-
ing configurations at C-3, C-6 and C-7 had been prepared by
us and the remaining two had been reported by Paquette and
co-workers. None of these diastereomeric triols was sclerophy-
tin F and so to identify the natural product it was necessary to
re-analyse and compare the original NMR spectroscopic data
to those reported for closely related cladiellin natural products.
Inspection of the data reported by Alam and co-workers for
sclerophytins E and F reveals some anomalies and raises
doubts about the assignments for both compounds.[3] The first
problem is that the mass spectrum given for sclerophytin F is
not consistent with the assigned molecular formula (C20H34O4).
The molecular ion is given as 363 whereas the mass of the mo-
lecular ion for sclerophytin F should be 338, if the molecular
formula is correct. The heaviest ion in the mass spectrum for
sclerophytin E appears at 338 which could mean that ionisa-
tion has resulted in loss of the acetate group or that this com-
pound is actually a triol with molecular formula C20H34O4. Final-
ly, the chemical shifts for the carbon framework signals in the
13C NMR spectra for sclerophytins E and F are almost identical
and the chemical shifts of the signals corresponding to C-3
differ by only d=0.3 ppm, which is inconsistent with sclero-
phytin E being the C-3 acetate of sclerophytin F. A chemical
shift difference of several ppm would be expected on the basis
of the observed differences in the 13C NMR spectra of sclero-
phytins A (3) and B (4), for example (Figure 1). The 1H NMR
spectra for sclerophytins E and F are also very similar and the
chemical shifts and coupling constants are identical for many
signals. It should be appreciated that comparison of data for
sclerophytins E and F is complicated by the fact that the origi-
nal publication describing their isolation contains significant ty-
pographical errors.[3]
[a] Data reported in ref. [2]. [b] Data reported in ref. [6], but peaks for C-3,
C-7, C-13, C-18 and C-19 appear to have been assigned incorrectly and
have been corrected. [c] Structure confirmed by X-ray analysis. [d] Data
reported in ref. [7]. [e] The 13C NMR spectrum was recorded in C6D6.
[f] Data reported in ref. [3].
products reassigned by Friedrich and Paquette as having an S
configuration at C-3, shows that the compounds are very simi-
lar (Table 5). Significant differences in chemical shift are restrict-
ed to signals corresponding to C-5–C-7, suggesting that the
C-6 substituent accounts for the structural differences between
the compounds.
1
The H and 13C NMR spectroscopic data reported for sclero-
phytins E and F are almost identical and sclerophytin F is clear-
ly not a diastereomer of sclerophytin A. Complete analysis of
the 13C NMR spectroscopic data for sclerophytin A (3) and the
seven other diastereomeric triols containing an R or S configu-
ration at C-3, C-6 and C-7, and comparison of these data to
those of the natural products 4–7, 6-ethoxy sclerophytin E, 6-
valeroyl sclerophytin E and litophynin E leads us to the conclu-
sion that sclerophytin F is simply re-isolated sclerophytin E,
a finding that is consistent with the original mass spectrometry
data.[3] Based on all the available data, and in particular com-
parison of the 13C NMR spectroscopic data for sclerophytin E
with those of sclerophytins A and C, it is clear that sclerophy-
tin E is the C-3 acetate of sclerophytin A. This is the structure
that was assigned to sclerophytin E by Alam and co-workers[3]
and by Rao, Faulkner and co-workers,[9] prior to the structural
reassignment of several sclerophytins by Friedrich and Pa-
quette in 2002.[11] The fact that sclerophytins E and F are the
same compound is particularly evident when one appreciates
that the 13C NMR spectroscopic data for the triols 9, 36, 41 and
42 show a much lower degree of homology than do the
13C NMR spectroscopic data for sclerophytins E and F, even
Inspection of the 13C NMR spectroscopic data for the closely
related natural products 3–6 (Figure 1),[2,6,7] the structures of
which have been verified by total synthesis or X-ray crystallog-
raphy, and comparison with the 13C NMR spectroscopic data
for sclerophytin F reveals some interesting trends (Table 4). It is
clear that the 13C NMR spectroscopic data for sclerophytin F
are very similar (ꢀ0.3 ppm chemical shift difference) to those
of sclerophytin A, apart from the chemical shifts of the signals
arising from C-2–C-5 and C-18. This observation suggests the
compounds are very similar but the C-3 hydroxyl group of scle-
rophytin F is functionalised in some way. Another significant
observation is that the 13C NMR spectroscopic data for sclero-
phytins E and F are very similar to those of sclerophytin C (7),
especially with regard to the signals arising from C-2–C-5 and
C-18. The only major differences are between the signals re-
sulting from the C-6–C-9, as a consequence of the C-8 hydroxyl
group in sclerophytin C (Table 4).
Comparison of the 13C NMR spectroscopic data for sclero-
phytins E and F with those of the other sclerophytin natural
Chem. Eur. J. 2015, 21, 1 – 10
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