Syntheses and Phytotoxicity of All Stereoisomers of 6-(2-Hydroxy-6-phenylhex-1-yl)-5,6-dihydro-2 H-pyran-2-one and Determination of the Effect of the α,β-Unsaturated Carbonyl Structure and Hydroxy Group Bonding to Chiral Carbon

Article abstract of DOI:10.1021/acs.jafc.9b05507

All four stereoisomers of naturally occurring 6-(2-hydroxy-6-phenylhex-1-yl)-5,6-dihydro-2H-pyran-2-one (1) were synthesized by employing yeast-reduction products with high optical purity [from 95% enantiomeric excess (ee) to more than 99% ee], and then their phytotoxicities against lettuce and Italian ryegrass were evaluated. In the Italian ryegrass seedlings test, (6S,2′R)-1 showed the most potent and stereospecific activity against the shoots (IC₅₀ = 260 μM) and roots (IC₅₀ = 43.2 μM), with a significant difference from other stereoisomers. The highest seed germination inhibitory activity against Italian ryegrass seed was also observed in (6S,2′R)-1, showing a 53% germination ratio from the control at 1000 μM. This advantageous (6S,2′R) stereochemistry was employed in the syntheses of α,β-dihydro, 2′-dehydroxy, and 2′-methoxy derivatives 13-15. By the test using these derivatives, the importance of the α,β-unsaturated double bond and hydroxy group bonding to a chiral center on the 6-alkyl chain of 5,6-dihydro-α-pyrone for phytotoxicity was determined. In the test against lettuce, the 6S configuration and (6S,2′S) configuration were necessary for growth inhibition (IC₅₀ = ca. 60 μM) and germination inhibition (63% germination ratio at 1000 μM), respectively.

Full text of DOI:10.1021/acs.jafc.9b05507

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Functional Structure/Activity Relationships
Syntheses and Phytotoxicity of All Stereoisomers of 6-
(2-Hydroxy-6-phenylhex-1-yl)-5,6-dihydro-2H-pyran-2-one
and Determination of Effect of #,#-Unsaturated Carbonyl
Structure and Hydroxy Group Bonding to Chiral Carbon
Ryota Ochi, Hisashi Nishiwaki, and Satoshi Yamauchi
J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.9b05507 • Publication Date (Web): 14 Oct 2019
Downloaded from pubs.acs.org on October 21, 2019
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Page 1 of 30
Journal of Agricultural and Food Chemistry
Syntheses and Phytotoxicity of All Stereoisomers of
6-(2-Hydroxy-6-phenylhex-1-yl)-5,6-dihydro-2H-pyran-2-one and Determination
of Effect of ,-Unsaturated Carbonyl Structure and Hydroxy Group Bonding to
Chiral Carbon
Ryota Ochi, Hisashi Nishiwaki, and Satoshi Yamauchi*
Graduate School of Agriculture, Ehime University, 3-5-7 Tarumi, Matsuyama, Ehime
790-8566, Japan
*Corresponding (Tel: +81-89-946-9846; Fax: +81-89-977-4364; E-mail:
yamauchi.satoshi.mm@ehime-u.ac.jp, syamauch@agr.ehime-u.ac.jp)
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ABSTRACT
All four stereoisomers of naturally occurring
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6-(2-hydroxy-6-phenylhex-1-yl)-5,6-dihydro-2H-pyran-2-one (1) were synthesized by
employing yeast-reduction products with high optical purity (95%ee–more than 99%
ee), and then their phytotoxicities against lettuce and Italian ryegrass were evaluated.
In the Italian ryegrass seedlings test, (6S,2´R)-1 showed the most potent and
stereospecific activity against the shoots (IC50 = 260 µM) and roots (IC50 = 43.2 µM)
with a significant difference from other stereoisomers. The highest seed germination
inhibitory activity against Italian ryegrass seed was also observed in (6S,2´R)-1,
showing 53% germination ratio from control at 1000 µM. This advantageous
(6S,2'R)-stereochemistry was employed in the syntheses of -dihydro, 2´-dehydroxy,
and 2´-methoxy derivatives 13-15. By the test using these derivatives, the importance
of ,-unsaturated double bond and a hydroxy group bonding to a chiral center on the
6-alkyl chain of 5,6-dihydro--pyrone for phytotoxicity was determined. In the test
against lettuce, 6S-configuration and (6S,2'S)-configuration were necessary for growth
inhibition (IC50 = ca. 60 µM) and germination inhibition (63% germination ratio at 1000
µM), respectively.
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Key words: 5,6-dihydro--pyrone; allelopathy; plant growth regulation; germination
inhibitory activity; phytotoxicity
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INTRODUCTION
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5,6-Dihydro--pyrone is a secondary metabolite biosynthesized by plants.
Antitumor activity and cytotoxicity,1-12 antiproliferative,13-14 antimicrobial,15-17
larvicidal,18 carbonic anhydrase inhibitor,19 spasmolitic,20 antiprotozoal,21,22
antifungal,23,24 and anti-inflammatory11 activity have been reported. The effect of
stereochemistry and structure-activity relationship have not been discussed in these
experiments. With regarding to the plant growth regulation, the phytotoxicities of 2-5
have been reported (Figure 1).25-28 We focused on the substituent of the alkyl chain at
6-position of the 5,6-dihydro--pyrone structure in this project on the phytotoxicity.
Although the polyacetate compound, (+)-boronolide (5), showed weak activity in our
previous study,28 the phenyl group and alkenyl substituent seem to be tolerable for the
phytotoxicity. The purpose of this project is to clarify the effect of the stereochemistry
and hydroxy group in the 6-alkyl group on the phytotoxicity. To promote this project,
the compound 1,23 which was isolated from Ravensara crassifolia, was selected as a
target compound because of the presence of a hydroxy group bonding to a chiral carbon
on the 6-alkyl chain. The stereochemistry of the natural compound 1 was revised to
(6S,2'S)-configuration29 after the first report. After syntheses of all four stereoisomers
of 1, the growth inhibitory and germination inhibitory activities against lettuce and
Italian ryegrass were examined. The stereospecific phytotoxicity of
5,6-dihydro--pyrone is first described in this article.
The syntheses of (6R,2'S)-130, (6S,2'R)-1,31-38 and both (6R,2'R)-1 and
(6S,2'R)-14 have been achieved. However, the synthetic report on (6S,2'S)-1 can not be
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found. We selected (1'R,2'S)-6 and (1'S,2'S)-6,17 which could be prepared from one
racemic compound by yeast-reduction,39 as the staring materials for the syntheses of all
four stereoisomers. Furthermore, the importance of the ,-unsaturated structure and
the hydroxy group bonding to a chiral center on the 6-alkyl chain for the phytotoxicity
was also determined by the preparations of the derivatives 13-15 and their biological
tests against plants.
MATERIALS AND METHODS
All test compounds were synthesized by the methods described in the
supporting information.
(R)-6-[(R)-2-Hydroxy-6-phenylhex-1-yl]-5,6-dihydro-2H-pyran-2-one
((6R,2'R)-1). colorless oil; []20D +56 (c 0.20, CHCl3); IR vmax (CHCl3) 3434, 2934,
1714, 1256, 1050 cm−1; 1H NMR (400 MHz, CDCl3)  7.29–7.16 (m, 5H), 6.89 (ddd, J
= 9.5, 4.3, 4.3 Hz, 1H), 6.01 (ddd, J = 9.7, 1.8, 1.8 Hz, 1H), 4.74 (m, 1H), 4.00 (m, 1H),
2.62 (t, J = 7.6 Hz, 2H), 2.34 (m, 2H), 2.13 (br, 1H), 1.87 (ddd, J = 14.5, 9.8, 2.2 Hz,
1H), 1.69–1.59 (m, 3H), 1.53–1.46 (m, 3H), 1.37 (m, 1H), 1.49 (m, 2H); 13C NMR (100
MHz, CDCl3)  164.5, 145.5, 142.4, 128.3, 128.2, 125.6, 121.2, 75.0, 66.9, 42.2, 37.8,
35.8, 31.4, 29.9, 25.1; MS (FAB) m/z 275 (M+H)+; HRMS (FAB) m/z calcd for
C17H23O3 275.1647 (M+H)+, found 275.1650; >99% ee (AD-H, 5% iso-PrOH in hexane,
1.0 mL/min, detected at 254 nm, tR30 min).
(6R,2'S)-1. colorless oil; []20D +84 (c 0.47, CHCl3); IR vmax (CHCl3) 3700,
3018, 1717, 1559 cm−1; 1H NMR (400 MHz, CDCl3)  7.29–7.26 (m, 2H), 7.19-7.16 (m,
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3H), 6.89 (m, 1H), 6.02 (ddd, J = 9.8, 1.9, 1.9 Hz, 1H), 4.65 (m, 1H), 3.85 (m, 1H), 2.63
(t, J = 7.7 Hz, 2H), 2.40 (m, 2H), 2.05 (br, 1H), 1.97 (ddd, J = 14.4, 8.6, 7.5 Hz, 1H),
1.79 (ddd, J = 14.4, 5.6, 3.6 Hz, 1H), 1.66 (m, 2H), 1.57–1.47 (m, 3H), 1.40 (m, 1H);
13C NMR (100 MHz, CDCl3)  164.0, 145.2, 142.4, 128.4, 128.3, 125.7, 121.2, 77.0,
69.1, 41.9, 37.5, 35.8, 31.4, 29.5, 25.1; MS (FAB) m/z 275 (M+H)+; HRMS (FAB) m/z
calcd for C17H23O3 275.1647 (M+H)+, found 275.1647; >99% ee (AD-H, 5% iso-PrOH
in hexane, 1.0 mL/min, detected at 254 nm, tR41 min).
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(6S,2'S)-1. colorless oil; []20 −56 (c 0.57, CHCl3); 95% ee (AD-H, 5%
D
iso-PrOH in hexane, 1.0 mL/min, detected at 254 nm, tR22 min).
(6S,2'R)-1. colorless oil; []20 −84 (c 0.19, CHCl3); 95% ee (AD-H, 5%
D
iso-PrOH in hexane, 1.0 mL/min, detected at 254 nm, tR34 min).
(S)-6-[(R)-2-Hydroxy-6-phenylhex-1-yl]-3,4,5-6-tetrahydro-2H-pyran-2-
one (13). colorless oil; []20D +28 (c 1.2, CHCl3); 1H NMR (400 MHz, CDCl3) 
7.28–7.25 (m, 2H), 7.17–7.15 (m, 3H), 4.50 (m, 1H), 3.80 (m, 1H), 2.64–2.54
(overlapped, 1H), 2.62 (t, J = 7.7 Hz, 2H), 2.43 (ddd, J = 17.7, 8.7, 7.2 Hz, 1H), 2.40 (br,
1H), 2.00–1.79 (m, 4H), 1.72–1.59 (m, 3H), 1.58–1.44 (m, 4H), 1.39 (m, 1H); 13C NMR
(100 MHz, CDCl3)  171.4, 142.4, 128.3, 128.2, 125.6, 79.6, 69.0, 43.0, 37.4, 35.8, 31.3,
29.3, 27.8, 25.0, 18.3; MS (FAB) m/z 277 (M+H)+; HRMS (FAB) m/z calcd for
C17H25O3 277.1796 (M+H)+, found 277.9796.
(R)-6-(6-Phenylhex-1-yl)-5,6-dihydro-2H-pyran-2-one (14). colorless oil;
[]20 −121 (c 0.21, CHCl3); 1H NMR (400 MHz, CDCl3)  7.29–7.25 (m, 2H), 7.18–
D
7.15 (m, 3H), 6.86 (ddd, J = 9.7, 5.0, 3.4 Hz, 1H), 6.01 (ddd, J = 9.9, 1.8, 1.8 Hz, 1H),
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4.40 (m, 1H), 2.60 (t, J = 7.7 Hz, 2H), 2.33–2.29 (m, 2H), 1.79 (m, 1H), 1.67–1.59 (m,
3H), 1.52 (m, 1H), 1.43–1.34 (m, 5H); 13C NMR (100 MHz, CDCl3)  164.5, 145.0,
142.6, 128.3, 128.2, 125.6, 121.4, 77.9, 35.9, 34.8, 31.3, 29.4, 29.2, 29.1, 24.7; MS
(FAB) m/z 259 (M+H)+; HRMS (FAB) m/z calcd for C17H23O2 259.1697 (M+H)+,
found 259.1698.
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(S)-6-[(R)-2-Methoxy-6-phenylhex-1-yl]-5,6-dihydro-2H-pyran-2-one (15).
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Colorless oil; []20 −93 (c 0.24, CHCl3); 1H NMR (400 MHz, CDCl3)  7.29–7.25 (m,
D
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2H), 7.19–7.16 (m, 3H), 6.88 (m, 1H), 6.03 (ddd, J = 9.7, 1.8, 1.8 Hz, 1H), 4.55 (m, 1H),
3.42 (dddd, J = 5.9, 5.9, 5.9, 5.9 Hz, 1H), 3.30 (s, 3H), 2.62 (t, J = 7.7 Hz, 2H), 2.38 (m,
2H), 2.07 (ddd, J = 14.5, 6.7, 6.7 Hz, 1H), 1.76 (ddd, J = 14.3, 5.9, 5.9 Hz, 1H), 1.69–
1.53 (m, 4H), 1.40 (m, 2H); 13C NMR (100 MHz, CDCl3)  164.4, 145.1, 142.4, 128.3,
128.4, 125.7, 121.4, 76.7, 75.3, 56.1, 38.3, 35.9, 32.9, 31.6, 29.5, 24.6. MS (FAB) m/z
289 (M+H)+; HRMS (FAB) m/z calcd for C18H25O3 289.1804 (M+H)+, found 289.1804.
Plant growth regulation activity and seed germination inhibitory activity.
The plant growth regulation activity of our synthesized all stereoisomers of 1 and 13-15
were evaluated using lettuce (Lactuca sativa L. Green-wave (Takii Seed Co. Ltd.,
Kyoto, Japan)) and Italian ryegrass (Lolium multiflorum Lam. Wase-fudo (Takii Seed
Co. Ltd.)) seedling. A sheet of filter paper (diameter = 90 mm) was put in a 90 mm
Petri dish and wetted with 500 μL of test sample solution dissolved in acetone at
concentrations from 6.0 to 0.15 mM or from 6.0×10−5 to 6.0×10−9 M. After the filter
paper had dried, 3 mL of water was poured into the dish to adjust the final concentration
from 1000 to 25 µM or from 10−5 to 10−9 M. Thirty seeds of each plant were placed on
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the filter paper, and the Petri dishes were sealed with parafilm. The Petri dishes were
then incubated in the dark at 20°C. The lengths of roots and shoots were measured
after 3 days for lettuce seedlings and after 5 days for Italian ryegrass seedlings by using
an ordinary ruler. The shoot and root lengths of the control were ca. 1 and 2 cm for
lettuce seedlings and 2 and 3 cm for Italian ryegrass seedlings, respectively.
Experiments were performed in triplicate for each sample at 1000 to 25 µM, and
conducted in singlicate for each sample at 10−5 to 10−9 M. In addition, the seed
germination inhibitory activity of our synthesized all stereoisomers of 1 and 13-15 were
evaluated using Italian ryegrass and lettuce seed. Preparing the Petri dish including
thirty seeds at 1000 µM by employing the same method, the petri dish was then
incubated in the dark at 20°C. The germinated seeds were counted after 4 days for
ryegrass and 3 days for lettuce, and the seed germination ratio of each compound
against control were calculated. The seed germination ratio of the control was ca. 80%
for ryegrass and 100% for lettuce. Experiments were performed in triplicate for each
sample. The data are presented as percentage differences from the control,
respectively.
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Evaluation of biological activity. Experiments were performed in triplicate
or more for each sample. Statistical analyses were conducted one-way ANOVA
followed by Tukey’s multiple-comparison test by using PRISM software ver. 5.0
(GraphPad software Inc., San Diego, CA, USA), and the values of p were considered to
be statistically significant. The value of IC50 (effective concentration for inducing
50% growth inhibitory ratio compared with control) was calculated when the
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concentration was 1000 to 25 µM. The data are presented as percentage differences
from the control when the concentration was 10−5 to 10−9 M.
RESULTS AND DISCUSSION
To synthesize the stereoisomers (6R,2'R)- and (6R,2'S)-1, the synthetic
sequence was started from the reported aldehyde (1'R,2'S)-617 (Scheme 1). The
aldehyde 6 was treated with 4-phenylbutylmagnesium bromide to give alcohols
(2R,1'R,2'S)-7 (40%) and (2S,1'R,2'S)-7 (38%). These secondary alcohols were
converted to the R- and S--methoxy--(trifluoromethyl)phenylacetic acid esters,
respectively, to determine the absolute configuration at the C2 positions by the modified
Mosher method (Figure 2).40 The S−R values of their 1H-NMR spectra of
(S)-(2R,1'R,2'S)-7 and (R)-(2R,1'R,2'S)-7 were negative at triisopropylsilyl group and the
C2' position, and the value was positive at the C6 position. On the other hand, the S−
R values of their 1H-NMR spectra of (S)-(2S,1'R,2'S)-7 and (R)-(2S,1'R,2'S)-7 were
positive at triisopropylsilyl group and the C2' position, and the value was negative at the
C6 position (Figure 2). After the protections of the hydroxy groups of (2R,1'R,2'S)-
and (2S,1'R,2'S)-7 as 4-methoxybenzyl ethers by using 4-methoxybenzyl bromide and
NaH, the desilylations with (n-Bu)4NF were performed, respectively. Pyridinium
chlorochromate oxidations of the resulting cyclopentanol derivatives (1S,2R,2'R)-9 and
(1S,2R,2'S)-9 followed by Baeyer–Villiger oxidations by employing
m-chloroperoxybenzoic acid afforded (6R,2'R)- and (6R,2'S)-11, respectively (Scheme
1). The introductions of the ,-unsaturated double bonds to these lactones with
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[Ph(SeO)]2O gave (6R,2'R)- and (6R,2'S)-12, respectively. Finally, the cleavages of
each p-methoxybenzyl ether by using trifluoroacetic acid gave (6R,2'R)- and (6R,2'S)-1.
The stereoisomers (6S,2'S)- and (6S,2'R)-1 were synthesized by the same synthetic
method from (1'S,2'S)-6.17 The enatiomeric excesses of 1–4 were determined as more
than 99%ee for (6R,2'R)- and (6R,2'S)-1. On the other hand, 95%ee was observed for
(6S,2'S)- and (6S,2'R)-1. The success of these syntheses enabled us to clarify the
phytotoxicities of stereoisomers of 1.
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The plant growth inhibitory activities of the synthesized stereoisomers 1
against lettuce and Italian ryegrass were evaluated (Table 1). Against lettuce, all
stereoisomers showed growth inhibitory activities against both the shoots (IC50 = 227–
491 µM) and roots (IC50 = 58.4–95.2 µM). The activities of (6S,2'R)- and (6S,2'S)-1
were higher than (6R,2'R)-1 with the significant difference, showing IC50 values of
200-300 M against the shoots and around 60 µM against roots. Although the
difference of activity levels against the shoots and roots was not wide and less than
2-fold, the 6S-absolute configuration would be more important than the 2'-absolute
configuration for the higher activity against lettuce. Against Italian ryegrass, the
growth inhibitory activity was also shown against both the shoots (IC50 = 260–741 µM)
and roots (IC50 = 43.2–131 µM) in all stereoisomers. The phytotoxicity of (6S,2'R)-1
was most potent against the shoots (IC50 = 260 µM) and roots (IC50 = 43.2 µM),
showing 2-3-fold more potent than the other stereoisomers with the significant
difference. The IC50 values against Italian ryegrass was broader than against lettuce.
The chiral centers at both the 6- and 2'-positions would be important. The tests at
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10-5–10−9 M showed neither the growth inhibition nor promotion against both lettuce
and Italian ryegrass.
To clarify an another phytotoxicities of the test compounds, the seed
germination inhibitory activities of stereoisomers of 1 against lettuce and Italian
ryegrass seeds were examined at 1000 µM (Figure 3). Against lettuce, only (6S,2'S)-1
showed lower germination ratio (63%) with the significant difference from the other
stereoisomers. The same stereoisomer (6S,2'S)-1 was effective for the growth
inhibition of lettuce. On the other hand, all stereoisomers exhibited the germination
inhibitory activity (germination ratio of 53%-70%) with the significant difference from
the control against Italian ryegrass. The (6S,2'R)-1 was most potent to show the
significant difference from (6R,2'R)-1 and (6S,2'S)-1. The (6S,2'R)-1 was a most
effective stereoisomer in both the growth and germination inhibitory activity against
Italian ryegrass. Since the germination inhibitory activities were not observed at 0.6 M,
the growth inhibitions observed in these stereoisomers were not due to the germination
inhibitory activities.
Based on the stereochemistry of the most effective stereoisomer (6S, 2'R)-1,
derivatives 13-15 were synthesized (Scheme 2) to evaluate the importance of the
,-unsaturated structure and the hydroxy group bonding to a chiral center for the
activity. The saturated derivative 13 was obtained by hydrogenolysis of (6S,2'R)-11
under H2 gas in the presence of Pd(OH)2/C. After the Grignard reaction of (1'S,2'S)-6,
the resulting secondary hydroxy group was mesylated. The treatment of the crude
mesylate with NaBH4 gave the dehydroxy product. This intermediate was converted
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to 2'-dehydroxy derivative 14 by the same synthetic method described above. To
prepare the 2'-methoxy derivative 15, the secondary hydroxy group obtained by
Grignard reaction to (1'S,2'S)-6 was methylated by using NaH and CH3I. The desired
stereochemistry was separated by silica gel column chromatography. After the
desilylation by n-Bu4NF, the resulting intermediate was converted to 15 by the same
method described above.
The plant growth inhibitory activities of derivatives 13-15 against lettuce and
Italian ryegrass were assessed (Table 1). Even if the stereochemistry was
(6S,2'R)-stereoisomer, the derivative 13 was inactive against both plants to suggest the
important role of the ,-unsaturated carbonyl structure. Michael acceptor properties
of (R)-5,6-dihydro-2H-pyran-2-one was reported against cancer cell lines.41) We found
this property in the plant growth inhibition. The allelopathic ,-unsaturated carbonyl
compounds have been reported,42,43) whose ,-unsaturated structures are assumed to
act as Michael accepters. The absence of the 2'-hydroxy group decreased the activity,
the derivative 14 showing 9-fold less potent than (6S,2'R)-1 against Italian ryegrass
roots. Against lettuce roots, more than 16-fold less potent activity was observed. As
for the effect on the growth of shoots, the only less than around 2-fold activity was
shown against lettuce and Italian ryegrass. Furthermore, the activity of 2'-methoxy
derivative 15 was 3-fold and more than 16-fold less potent than (6S,2'R)-1 against
lettuce shoots and roots, respectively. Against Italian ryegrass shoots and roots, 3-fold
and 8-fold less potent activities were shown. Even if the ,-unsaturated structure is
presence, the activities of 14 and 15 decreased. Both the ,-unsaturated carbonyl
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structure and hydroxy group bonding to a chiral carbon affect the growth inhibition of
roots than shoots. Comparing with polyacetate compound, (+)-boronolide (5), the
activity of (6S,2'R)-1 was dramatically increased. This fact suggested that the presence
of 2'-hydroxy group, chiral center, and phenyl group on the 6-alkyl chain was necessary
for the higher activity. These results suggest the molecular target of
6-(2-hydroxy-6-phenylhex-1-yl)-5,6-dihydro-2H-pyran-2-one 1 in the plant cells. It
seems that the 6-oxygen, 2'-hydroxy group, and phenyl group would react to an active
site after binding of enone part to a binding site. The (6S,2'R)-stereochemistry would
be most advantageous for the reaction to an active site of Italian ryegrass. In the
germination inhibitory activity against Italian ryegrass, all derivatives 13-15 exhibited
lower activity than (6S,2'R)-1 as shown in the growth test, demonstrating the significant
role of ,-unsaturated carbonyl structure, 2'-hydroxy group bonding to the 2'-chiral
center for the higher activity (Figure 3). These facts also suggest the role of the
binding site of enone part and active site of the chiral positions.
In summary, we synthesized all stereoisomers of
6-(2-hydroxy-6-phenylhex-1-yl)-5,6-dihydro-2H-pyran-2-one with high optical purities
(95%ee–more than 99% ee). For the growth inhibition against lettuce, the
6S-configuration was important. As for the germination inhibition against lettuce,
(6S,2'S)-1 was most potent. Additionally, we clarified that (6S,2´R)-1 was most
effective for the growth inhibitory and the seed germination inhibitory activities against
Italian ryegrass. The crucial roles of the ,-unsaturated carbonyl structure and the
hydroxy group bonding to 2'-chiral carbon for these activities were revealed. It was
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suggested that the phytotoxicity of (6S,2´R)-1 is higher than that of phytotoxic natural
lignans.44-47 The stronger stereospecific activity of 5,6-dihydro-2H-pyran-2-one than
that of lignans was also shown.
ASSOCIATED CONTENT
Supporting Information
Supporting Information is available free of charge on the ACS Publications website at
DOI:
Syntheses of compounds. NMR and MS data of intermediates 6-12 and the final
compounds 1, 13-15. NMR and MS spectra of the final compounds 1, 13-15. HPLC
data of all stereoisomers of 1 (PDF).
AUTHOR INFORMATION
Corresponding Author
(S.Y.) Phone: +81-89-946-9846. Fax: +81-89-977-4364. Email:
yamauchi.satoshi.mm@ehime-u.ac.jp, syamauch@agr.ehime-u.ac.jp.
Funding
We thank to Marutomo Corporation for funding.
ACKNOWLEDGMENT
Part of this study was performed at Advanced Research Support Center (ADRES) in
Ehime University.
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Table 1. Plant growth inhibitory activity of all stereoisomers and derivatives 13-15
(IC50: µM±SE, n = 3). In the case of IC50 >1000 µM, % from control is shown.
a-b: p<0.05, a-c: p<0.001
Compounds
Lettuce
Italian Ryegrass
Shoots
491 ± 75a
Roots
Shoots
Roots
95.2 ± 7.0a
625 ± 63a
127 ± 10a
114 ± 6.4a
131 ± 8.8a
43.2 ± 4.1c
363 ± 27ab 73.9 ± 3.8ab
741 ± 41a
548 ± 96a
260 ± 20b
227 ± 20b
303 ± 32b
58.4 ± 4.2b
62.3 ± 5.3b
>1000 (-7%) >1000 (-27%) >1000 (-12%) >1000 (-33%)
549 ± 11
>1000 (-18%)
695 ± 98
772 ± 12
409 ± 43
377 ± 55
>1000 (-34%) >1000 (-27%)
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Figure caption
Figure 1. All stereoisomers of
6-(2-hydroxy-6-phenylhexyl)-5,6-dihydro-2H-pyran-2-one 1 and phytotoxic
6-substituted 5,6-dihydro--pyrone 2–4.
Scheme 1. Syntheses of all stereoisomers of
6-(2-hydroxy-6-phenylhexyl)-5,6-dihydro-2H-pyran-2-one 1
Figure 2. Chemical shift differences (S−R) of (S)- and
(R)--methoxy--(trifluoromethyl)phenylacetic acid esters.
Figure 3. Seed germination ratio of lettuce and Italian ryegrass at 1000 M (% ± SE, n
= 3). Statistically significant differences are represented by different letters above the
bars (on-way ANOVA, Tukey post-test, P<0.05).
Scheme 2. Syntheses of 6-substituted 5,6-dihydro--pyrone derivatives 13-15.
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Figure 1
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Figure 3
(A)Germination inhibitory activity of stereoisomers 1 against lettuce
control (6R,2′R)-1 (6R,2′S)-1 (6S,2′S)-1 (6S,2′R)-1
504
505
(B) Germination inhibitory activity of stereoisomers 1 against Italian ryegrass
control (6R,2′R)-1 (6R,2′S)-1 (6S,2′S)-1 (6S,2′R)-1
506
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(C) Germination inhibitory activity of derivatives 13-15 against Italian ryegrass
control (6S,2′R)-1
13
14
15
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