Phytochemistry Letters
Short communication
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Using NMR to determine the relative stereochemistry of 7,7-diaryl-8,8 -
dimethylbutan-1-ol lignans
Samuel J. Davidson, Claire E. Rye, David Barker*
School of Chemical Sciences, University of Auckland, 23 Symonds St., Auckland, New Zealand
A R T I C L E I N F O
A B S T R A C T
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Article history:
Received 9 July 2015
Received in revised form 25 September 2015
Accepted 28 September 2015
Available online 20 October 2015
Due to their linear, freely rotatable, structure many natural 7,7-diaryl-8,8 -dimethylbutan-7 -ol lignans
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are reported without any stereochemical assignment. Analysis of synthetic 8,8 -dimethylbutanol lignans
and analogues reveals significant differences between the NMR data of syn- and anti-isomers. This
informationwas then used to determine the relative stereochemistry of the C-8 and C-8 methyl groups in
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previously undefined natural products.
ã 2015 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved.
Keywords:
Lignans
Butanol lignans
Seco lignans
Stereochemical analysis
Lignans are a broad class of plant secondary metabolites formed
from the oxidative dimerization of two phenyl propanoid units.
The different positions for oxidative coupling gives rise to the
various structural classes of lignans. An interesting class of lignans,
the 7,7-diarylbutanol seco-lignans, have been reported to have
cytotoxic [1], anti-HIV-1 [2] and antioxidant [3] bioactivity (e.g.
Schisandra lignan (1), Fig. 1) and synthetic analogues of these have
shown even higher bioactivity [4]. Due to their acyclic structure
with many freely rotatable bonds natural 7,7-diarylbutanol lignans
are frequently reported in the literature with no relative
stereochemical assignments and many of which are reported as
(Table 1). Therefore it would be helpful and important to
understand the relative stereochemical relationship between the
two methyl groups at C-8 and C-8 , as this would reduce the
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number of isomers required to determine the absolute stereo-
chemistry of these interesting seco-lignans. Acetate forms of 7,7-
diarylbutanol lignans have also been isolated, henricine B (8) –
from Schisandra henryi [11], and lignan 9 – from Schisandra
sphenanthera which has been reported as having anti-HSV and
anti-adenovirus activity [12], and have been reported without
stereochemical assignments (Table 2).
Previously, assignments of stereochemistry of these butanol
type lignans have been achieved by chemical transformation to a
known cyclic aryltetralone lignan (e.g. lignan 6 to lignan 6a, Fig. 1)
[13]. Others have used nOe analysis [14] and Newman projections
[15] (lignan 7), however due to the number of freely rotatable
bonds in these butanol lignans, these methods of stereochemical
analysis are non-reliable.
having chirality. Kadangustin
angustifolia [5], has a reported
J
(2), isolated from Kadsura
of +4.9 whereas a subsequent
ꢀ
a
D
synthesis of the enantiomer of kadangustin J (2) found an
D
a of
ꢀ
ꢁ
20.7 [6]. Schisandra lignan (1), isolated from Schisandra
propinqua (Wall.) Baill. [1], also had dissimilar rotations from an
asymmetrically prepared sample [7]. Syntheses of both Schisandra
lignan (1) [7] and kadangustin J (2) [6,8] have allowed for the
determination of a stereochemical relationship between the two
methyl groups. Other lignans in this class, schilancifolignan D (3) –
isolated from Schisandra lancifolia [9], marphenol G (4) – from
Schisandra wilsoniana [10], and kadangustin K (5) – from Kadsura
angustifolia [5], have been reported with undefined relative
stereochemistry and have not been synthesised (Fig. 2). These
lignans have three chiral centres compared to that of kadangustin J
Our group has previously synthesised a range of syn-dimethyl-
7,7-diarylbutanol lignans, including kadangustin J (2) [6]. During
this previous work we observed that the NMR data from reported,
but stereochemically undefined, lignans was significantly varied.
This led us to speculate that these variations were due to the
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compounds being either syn- or anti-8,8 -dimethyl-7,7-diary-
lbutanols. We therefore theorized that if each stereoisomer was
prepared it would allow for comparisons between the two isomers
and perhaps differences could be seen that would allow for a
simplified method of characterisation of isolated lignans.
(
2) and Schisandra lignan (1) which only have two chiral centres
The 7,7-diarylbutanol lignan analogues 10a–d were synthesised
following our reported procedure, which utilises the rearrange-
ment of 1,4-diarylbutan-1,4-diols 11a–d [16]. The syn-8,8
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874-3900/ã 2015 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved.
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